Dr Robert O. Becker: Silver Iontophoresis (Regeneration by
Silver Ions)

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**Dr Robert O. BECKER**

**Silver Ionotophoresis**

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**Robert O. Becker**, M. D.: Retired Prof.
of Medicine at Upstate Medical Center, Syracuse; Director of
Orthopedic Surgery at the Veterans Hospital, Syracuse, New
York; Author: *Cross Currents* and *The Body Electric*

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**<http://www.silverinstitute.org/news/4a1999.html>**  
**www.lifesilver.com**

**"Silver Helps Regrow Tissues in
Hundreds of Patients - Destroyed Cells Regenerate With
Silver-Based Procedure"**

**by Samuel Etris**   
**Senior Technical Consultant to The Silver Institute**

Silver can help regenerate human cells that have
been destroyed by disease or damaged in accidents.

The silver-based procedure has been so
successful in clinical tests, that one patient who had
sustained three crushed fingers in an accident grew new tissue
immediately. Within 2-1/2 months, skin coverage was complete
and there was normal, full sensation, good blood supply and
all joints had a normal range of motion. If left untreated,
the 3~year-old electrician's fingers would have fallen off
after turning black with gangrene, and he would have been left
with a totally useless hand. In fact, his orthopedic surgeon
recommended amputation of al1 three fingers, but the patient
requested silver-ion therapy that was successful.

The mechanism by which silver ions help rebuild
tissue has been studied for more than a decade by Robert O.
Becker, M. D., Becker Biomagnetics, Lowville, New York. Becker
first reported his findings at the First International
Conference on Silver and Gold in Medicine, cosponsored by The
Silver Institute in 1987.

In the decade since, this technique has been
used in a clinical setting at Mountain Medical Specialties in
Lakemont, Georgia, where hundreds of patients with various
wounds have recovered. In addition, a laboratory study
conducted by the U.S. Army Institute for Surgical Research in
Fort Sam Houston, Texas, showed that laboratory animals with
burn wounds treated under controlled conditions experienced
shortened time for reconstruction with silver-nylon dressings.
Recovery of skin function was faster when electric current was
applied compared to no application of electric current.

Becker discovered that when positively charged
silver ions are electrically introduced into wounds with a
proprietary silver-coated nylon fabric used as the positive
electrode, large amounts of primitive embryonic stem cells are
produced. These stem cells are responsible for the
reconstruction of destroyed tissue at a pace considerably
faster than if the wound had been left to heal by itself. In
other cases, the wound might not heal at all without the
introduction of these stem cells

"The advantages of this technique," says Becker,
"are the ease of use, use of the patient's own cells, no
immune reaction, no need to use human fetusus as a source of
stem cells, no need for anti-rejection drugs and it is
economic." [bag - the pharmas just hate that]

On September 29, 1998, Becker received a U.S.
patent (5,814,094) for the devices, materials and techniques
involved in regeneration of tissue using silver ions.

After several hundred cases, Becker believes
that the technique works in three stages. The first stage is
the chemical combination of the highly active free silver ions
with all bacteria or fungi present in the wound that are
inactivated within 20 to 30 minutes. The second stage occurs
over the next few days. Silver acts on fibroblast cells (the
cells that normally cause wound healing by scar formation) to
cause them to revert to their embryonic state, becoming stem
cells. These cells are universal building blocks whose role is
to reconstruct new tissue regenerating the original structure
rather than simply to form scar tissue only.

In the final stage, silver ions form a complex
with the living cells in the wound area to produce immediately
convertible stem cells. As stem cells flood the wound, they
are rapidly converted into new, mature normal tissues of the
types present before the wound occurred. The end result of
this conversion is complete restoration of all anatomical
structures including nerves and blood supply with no scar
formation. In all cases treated, no evidence of argyria
(discoloration of skin) or any other side effect was noted.

No other known treatment provides sufficient
numbers of the embryonic or stem cells required for true
regeneration of damaged or destroyed tissue in humans and
animals. This success indicates that there is the potential
not only for the healing of near-surface wounds, but for
regenerative repair of internal organs such as the heart,
liver, brain and the spinal cord.

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**US Patent # 5,814,094**

**Iontopheretic System for Stimulation
of Tissue Healing and Regeneration**

**( 9-29-1998 )**

**Becker, Robert O., et al.**

![](usp.jpg)

Classification:  - international: A61N1/30;
A61N1/30; (IPC1-7): A61M5/32; - european: A61N1/30B2; US: **607/50**
; 604/20

Also published as: US Patent # 7,005,556

**Abstract ---** An iontophoretic system for
promoting tissue healing processes and inducing regeneration.
The system includes a device and a method, a composition, and
methods for making the composition in vitro and in vivo. The
system is implemented by placing a flexible, silver-containing
anode in contact with the wound, placing a cathode on intact
skin near the anode, and applying a wound-specific DC voltage
between the anode and the cathode. Electrically-generated
silver ions from the anode penetrate into the adjacent tissues
and undergo a sequence of reactions leading to formation of a
silver-collagen complex. This complex acts as a biological
inducer to cause the formation in vivo of an adequate blastema
to support regeneration.

**References Cited:**   
**U.S. Patent Documents ---** 3799162 ~ 3800792 ~ 4312340
~ 4528265 ~ 4767401 ~4818697 ~ 4847049 ~ 4932951 ~ 4937323 ~
5322520 ~ 5324275

**Other References:**   
R O. Becker, et al., "Electrochemical Mechanisms and the
Control of Biological Growth Processes," in Modern Aspects of
Electrochemistry, No. 10, pp. 289-338, publ. Plenum Press
(1971). USA. .   
R. E. Hall, et al., "Inhibitory and Cidal Antimicrobial
Actions of Electrically Generated Silver Ions," J. Oral &
Maxillofac. Surg., vol. 45, pp. 779-784 (1987). USA. .   
R. O. Becker, et al., "Experience With Low-Current Silver
Electrode Treatment of Nonunion," in Electrical Prop. Bone
& Cartilage (ed. C. T. Brighton, et al.), Grune &
Stratton (1979), USA. .   
J. A. Spadaro, et al., "Experience With Anodic Silver in the
Treatment of Osteomyelitis," 25th Ann. ORS Mtg., Feb. 20-22,
1979. .   
R. O. Becker, et al., "Treatment of Orthopaedic Infections
With Electrically Generated Silver Ions," J. Bone & Joint
Surgery, vol. 60-A, pp. 871-88 (1978). USA. .   
R. O. Becker, et al., "Clinical Exp. With Low Intensity Direct
Current Stimulation of Bone Growth," Clin. Orthop. & Rel.
Res., vol. 124, pp. 75-83 (1977) . USA. .   
T. J. Berger, et al., "Antifungal Properties of Electrically
Generated Metallic Ions," Antimicrob. Agents & Chemother.,
vol. 10, pp. 856-860 (1976). USA. .   
T. J. Berger, et al., "Electrically Generated Silver Ions:
Quantitative Effects on Bacterial & Mammalian Cells,"
Antimicrob. Agents & Chemother., vol. 9, pp. 357-358
(1976) USA. .   
J. A. Spadaro, et al., "Some Specific Cellular Effects of
Electrically Injected Silver & Gold Ions," bioelectrochem.
& Bioenergetics, vol. 3, pp. 49-57 (1976. USA. .   
J. A. Spadaro, et al., "Antibacterial Effects of Silver
Electrodes With Weak Direct Current," Antimicrob. Agents &
Chemother., vol. 6, pp. 637-642 (1974). USA. .   
M. R. Urist, et al., "Bone Morphogenesis in Implats of
Insoluble Bone Gelatin," Proc. Nat. Acad. Sci. USA, vol. 70,
No. 12, Part I, pp. 3511-3515 (1973). USA.

***Description***

**BACKGROUND OF THE INVENTION**

**1. Field of the Invention**

The present invention relates to an
iontophoretic system for the stimulation of tissue healing and
regeneration. In particular, the present invention relates to
a method and device for stimulation of tissue healing and
regeneration, a composition for use therewith, and methods for
making the composition.

**2. Discussion of Background**

Healing, like all other biological processes, is
a cellular process. The occurrence of an injury immediately
triggers the onset of this process, which continues until the
injury is healed. Although its exact mode of action is not yet
understood, it is clear that a feedback mechanism monitors the
extent of tissue damage and adjusts cellular activity in the
injured area to produce the exact amount of healing needed.

As used herein, the terms "wound" and "injury"
refer to tissue damage or loss of any kind, including but not
limited to cuts, incisions (including surgical incisions),
abrasions, lacerations, fractures, contusions, burns, and
amputations.

Healing processes can be classified into three
types, determined by how the cells in the injured area react
to the injury. The simplest type of healing is scarification
healing, wherein cells at the edges of a wound produce
collagen and elastic fibers which simply bind the edges of the
wound together without restoring severed nerves or blood
vessels. This type of healing produces a visible scar, and
sometimes results in numbness and circulatory inadequacy in
the region of the wound and regions distal thereto. In the
higher animals, including man, the heart, skeletal muscle, and
nerve tissue (including the brain) heal by scarification.

A second type of healing is tissue replacement,
wherein the cells of some body tissues produce more cells of
their own kind to replace missing portions. In humans, the
skin and portions of the gastrointestinal tract heal by
replacement. In this type of healing, the replacement rate of
the cells in the injured area increases to produce sufficient
numbers of cells to help heal the injury, then returns to
normal after healing is complete. Replacement is effective
only if enough normal cells of the needed types are present in
the area, and only for the particular types of cells that are
capable of healing in this manner. Replacement is often
inadequate for healing full-thickness skin wounds, which
frequently heal with limited re-epithelialization, resulting
in poorly innervated, thin and inelastic skin, while
subcutaneous soft tissue defects heal primarily by
scarification. However, such results are generally adequate
for function if the wound is on the torso or the extremities
(excepting the hand).

The most effective--and most complex--type of
healing is regeneration. This type of healing is capable of
replacing entire limbs and internal organs, and even portions
of the brain and heart. Regeneration is a biphasic process. In
the first phase, normal, mature cells at the site of the
injury revert to an embryonic, unspecialized form
("de-differentiate"). These cells multiply rapidly, then
become activated and demonstrate a variety of energetic
processes which may include amitotic division, nuclear
transfer, migration of free nuclei into residual tissues, and
production of exceptionally large cells containing nuclear
material from a number of individual de-differentiated cells
(thus, "activated cells" are cells that undergo these
processes). Activation results in the rapid accumulation of a
large mass of embryonic cells known as the blastema, which is
the essential element for regeneration. The blastema may be
viewed as providing the biological raw material needed for
rebuilding the missing tissues: formation of an adequate
blastema results in complete regeneration of the missing
tissues, whereas if the blastema is inadequate in size, only
partial or incomplete regeneration takes place (formation of a
stunted or incomplete part, or merely regeneration of
individual tissue types that are not fully organized into the
desired structure).

In the second phase of the regeneration process,
the embryonic cells of the blastema respecialize
("re-differentiate") into the various types of cells needed to
rebuild the missing tissues and organized structures in
complete anatomical detail. The rebuilding process is
essentially a recapitulation (albeit on a local scale) of the
original embryonic development of the tissues being replaced.

In vertebrates, regenerative healing is found in
certain species of amphibians (notably salamanders). It is
almost totally lacking in humans, except in the fetus and in
very young children (who may regenerate the distal finger tip
if the wound is left open). In adults, regeneration is largely
limited to parts of the fracture healing process. Clearly, it
would be beneficial if humans could regenerate other damaged
tissues, both in terms of more cost-effective treatment
modalities and improved outcomes for patients.

The stimulus which initiates the complex
regenerative process in amphibians has been reported to be a
specific type of electrical signal, but the mechanism which
provides the blueprint for the tissues to be regenerated is
largely unknown. In the case of regeneration of individual
tissues, however, a number of inducer substances that carry a
specific signal causing either embryonic, de-differentiated,
or mature cells to convert into specific tissue types have
been identified. These "biological inducers" are analogous to
chemical catalysts in that they effect cellular transformation
by contact with the cells, but the inducer itself does not
take part in the transformation. It is believed that
biological inducers act by producing a signal in the nature of
a specific electrical field which causes an event to occur on
the surface of the target cell, which in turn causes the DNA
in the target cell to alter the cell type in a specific
fashion. By way of example, a "bone induction material" that
causes the transformation of muscle cells into bone has been
identified (M. Urist, Proc. Nat. Acad. Sci. USA, Vol. 70, pp.
3511-3515 (1973)).

Healing in general is known to be related to the
degree of the injury, the amount of nerve tissue present at
the site, and the electrical potential difference between the
site and surrounding intact tissue (the "current of injury").
In particular, regeneration in amphibians such as salamanders
and fracture healing in mammals are associated with complex
changes in the local DC (direct current) electric field. An
injury results in changes in the electric field and stimulates
the animal's neural system, which in turn produces an
electrical signal at the site of the injury, stimulating the
complex cellular responses that eventually produce healing.
The electric field gradually returns to normal, pre-injury
levels as the injury heals. Conversely, failure of the normal
healing process, as in fracture nonunions, is associated with
the absence of appropriate electrical signals at the site of
the injury.

These observations have lead to widespread use
of electrical stimulation for the treatment of injuries in
humans, especially fracture nonunions. Many studies have
demonstrated that the application of small electrical currents
(in the microampere range or lower) or weak magnetic or
electric fields affects the growth or reunion of bone. See,
for example, R. 0. Becker and A. A. Pilla, "Electrochemical
Mechanisms and the Control of Biological Growth Processes," in
Modern Aspects of Electrochemistry (ed. J. O'M. Bockris and B.
E. Conway), Vol. 10, pp. 289-338 (1971); R. 0. Becker, et al.,
"Clinical Experiences With Low Intensity Direct Current
Stimulation of Bone Growth," Clinical Orthopedics &
Related Research, Vol. 24, pp. 75-83 (1977); R. 0. Becker
& J. A. Spadaro, "Experience with Low Current Silver
Electrode Treatment of Nonunion," in Electrical Properties of
Bone and Cartilage (ed. C. Brighton, et al.), pp. 631-638
(1979); R. O. Becker, et al., "Clinical Experience with Low
Intensity Direct Current Stimulation of Bone Growth," Clinical
Orthopedics and Related Research, Vol. 124, pp. 75-83 (1977).

Furthermore, electrically-injected silver ions
are known to have significant antibacterial and antifungal
properties. Silver is a well-known antibiotic, widely used in
topical applications in the form of silver nitrate solution,
silver sulfadiazine, and so forth. However, the useful
antibacterial effect of such compounds is limited and due only
to the small amount of free silver ions produced by
dissociation of the compound or to formation of toxic
by-products (for example, use of silver nitrate (AgNO.sub.3)
solutions may lead to the formation of nitric acid). The
antibacterial action of these ions is limited to a very
localized effect directly on the wound surface.

Electrically-generated silver ions, on the other
hand, penetrate at least approximately 1 cm into the wound and
can be produced in much larger amounts than is possible with
topical preparations such as silver sulfadiazine. Thus,
electrically-injected silver is effective even against
antibiotic-resistant strains, inhibiting bacterial growth in
vivo and in vitro at current densities as low as 10
nA/mm.sup.2 and concentrations as low as 0.5 mg/ml.
Susceptible organisms include S. aureus, E col., Candida and
Torulopsis. These effects are described in a number of
publications, including the following: J. A. Spadaro, et al.,
"Antibacterial Effects of Silver Electrodes with Weak Direct
Current," Antimicrobial Agents and Chemotherapy, Vol. 6, pp.
637-642 (1974); J. A. Spadaro and R. 0. Becker, "Some Specific
Cellular Effects of Electrically Injected Silver and Gold
Ions," Bioelectrochemistry and Bioenergetics, Vol. 3, pp.
49-57 (1976); T. J. Berger, et al., "Antifungal Properties of
Electrically Generated Metallic Ions," Antimicrobial Agents
and Chemotherapy, Vol. 10, pp. 856-860 (1976); J. A. Spadaro
and R. 0. Becker, "Experience With Anodic Silver in the
Treatment of Osteomyelitis," Proceedings of the 25th Annual
Orthopedic Research Society Meeting, Vol. 4, p. 10 (1979); R.
0. Becker, et al., "Treatment of Orthopedic Infections With
Electrically-Generated Silver Ions," Journal of Bone and Joint
Surgery, Vol. 60A, pp. 871-881 (1978).

At any particular silver concentration,
electrically-generated silver ions are more effective in
inhibiting bacterial growth than silver salts (T. J. Berger,
et al., "Electrically Generated Silver Ions: Quantitative
Effects on Bacterial and Mammalian Cells," Antimicrobial
Agents and Chemotherapy, Vol. 9, pp. 357-358 (1976); Hall, et
al., "Inhibitory and Cidal Antimicrobial Actions of
Electrically Generated Silver Ions," J. Oral and Maxillofac.
Surg., Vol. 45, pp. 779-784, 1987).

Becker (U.S. Pat. No. 4,528,265) has disclosed
processes and products that involve subjecting mammalian cells
to the influence of electrically-generated silver ions. Anodic
silver causes cells such as mammalian fibroblasts to assume a
simpler, relatively unspecialized form and to resemble
dedifferentiated or embryonic cell types. In mammals,
including humans, this effect is associated only with the
silver ions; the effect is not related to the electrical
current or voltage. The afore-mentioned publications are
incorporated herein by reference.

A variety of devices for use in electrical
stimulation are known. Liboff, et al. disclose a noninvasive
magnetic field generator for producing a controlled,
fluctuating, directionally oriented magnetic field parallel to
an axis projecting though the target tissue (U.S. Pat. No.
4,932,951). An externally-generated magnetic field can be
combined with the local magnetic field to produce a resultant
field that enhances transfer of ions such as Ca.sup.++ across
the membrane of a living cell (Liboff, et al., U.S. Pat. No.
4,818,697).

Other devices make use of the antimicrobial
properties of silver and other metals. Raad, et al. (U.S. Pat.
No. 5,324,275) disclose a catheter tube surrounded by two
parallel helical conductors made of copper, gold, silver or
other heavy metals. When connected to a DC power source such
as a 9-volt battery, ions are transferred between the
conductors through body fluids, and induce an antimicrobial
effect proximate the area between the conductors.

Milder (U.S. Pat. No. 5,322,520) describes a
material containing dissimilar metal powders, such as silver
and gold, silver and copper, or silver and platinum mixed into
a conductive polymer substrate. When contacted by an
electrolytic solution, each metal granule that contacts the
electrolyte becomes either an anode or a cathode, so the
material contains an array of small batteries. Metal ions are
driven into the solution to kill bacteria on and near a device
to which the material is affixed. The material can be used in
devices such as catheters, cardiac pacemaker leads,
artificial; hip joints, and so forth.

Seiderman (U.S. Pat. No. 4,767,401) describes a
method for iontophoretic administration of medicaments such as
silver protein (a colloid of silver with protein). The
medicament is coated onto a metallic foil electrode so that,
when in contact with a wound, natural body fluids and the
negative electric charge of the wound site create a voltaic
effect that causes the medicament to migrate into the wound.

Yamamoto (U.S. Pat. No. 4,847,049) and McKnight,
et al. (U.S. Pat. No. 3,800,792) disclose collagen
compositions used for wound treatment. Yamamoto contacts
renatured collagen with a silver-ion-containing solution at pH
between 4.0 and 9.0, forming a composition wherein silver ions
are chelated to functional groups in the collagen. The
composition is then exposed to UV radiation to strengthen the
binding of the silver ions to the collagen. When the
composition contacts bodily fluids, the silver ion is slowly
released to protect the collagen from fungal and bacterial
attack. McKnight's laminated collagen dressing is made from a
layer of reconstituted collagen film laminated to a thin
continuous layer of an inert polymer material such as
polyurethane. Preferably, the collagen film contains finely
divided silver metal particles, added by soaking the dried
film in Tollen's reagent ((AgNH.sub.3).sub.2 OH) for 5 minutes
to oxidize excess glutaraldehyde and deposit silver metal on
the accessible surfaces of the collagen fibers.

Silver, et al. (U.S. Pat. No. 4,937,323) dress a
wound with a biocompatible, biodegradable collagen product and
apply low intensity direct current in the range of 10-100
microamperes. The collagen product may be a sponge made of
collagen powder or flakes, and contains electrodes made of
carbon or metal inserted therein. Donadelli (U.S. Pat. No.
4,312,340) treats scarred skin using a solution containing
embryonic placenta, collagen and vitreous humor extracts
diluted in distilled water, treated by partial electrolysis to
provide a formation of groups of amino acids. A variable low
frequency electric field is applied to create an electric
charge below the scarred area. Romero-Sierra, et al. (U.S.
Pat. No. 3,799,162) apply histamine to a lesion, and then
radiate the cells bounding the lesion with low intensity
nonionizing electromagnetic radiation to stimulate production
of collagen at the site.

Despite the wide variety of known treatment
modalities, no known treatment produces sufficient numbers of
the de-differentiated (i.e., embryonic) cells required for
true regeneration in humans and other mammals. In fact, the
treatment of injuries involving traumatic loss of skin and
soft tissue, particularly for hand injuries, ranges from
judicious neglect to major surgery. In the case of hand
injuries, the twin requirements of flexibility and sensation
mean that the above-described natural and enhanced healing
processes are inadequate to yield good functional results.

There is a need for a flexible, effective system
that helps promote and enhance tissue healing processes in
mammals, including humans. Use of such a system would not only
improve the outcome of the processes responsible for most
healing in humans (scarification, tissue replacement), but
would, in appropriate instances, induce true regenerative
healing resulting in regrowth of the specific tissue types
appropriate to the situs of the injury (normally innervated,
full thickness skin, subcutaneous soft tissues, bone, etc.).
The system would make use of simple, efficient delivery
devices, be safe and easy to use, and be capable of being
applied directly to the wound site.

**SUMMARY OF THE INVENTION**

According to its major aspects and broadly
stated, the present invention is an iontophoretic system for
promoting tissue healing processes and inducing regeneration.
The system includes a device and a method, a composition, and
methods for making the composition in vitro and in vivo. The
system is implemented as follows: a flexible,
silver-containing anode is placed in contact with the wound, a
cathode is placed on intact skin near the anode, and a
wound-specific DC voltage is applied between the anode and the
cathode.

Electrically-generated silver ions from the
anode penetrate into the adjacent tissues and undergo a series
of three reactions. First, the silver ions combine with
proteins, peptides and various other chemical species normally
present in solution in the tissues. The silver ions also
combine with any bacteria, fungi or viruses present in the
treatment area. If treatment is continued after all or most
available sites for this type of reaction have been exhausted,
the newly-generated silver ions associate with cells in the
region, particularly fibroblast cells and epithelial cells,
resulting in de-differentiation of these cells into embryonic
cell types. Then, if treatment is continued after this second
reaction is substantially complete, the free silver ions form
a complex with collagen fibers present in the wound. This
silver-collagen complex is believed to act as a biological
inducer to activate the previously-produced de-differentiated
fibroblast or epidermal cells to multiply and produce an
adequate blastema.

In mammalian-including human-wounds treated at
appropriate, wound-specific voltages, for a sufficient period
of time to carry out the above-described reactions, and with
anodes capable of supplying a sufficient number of silver ions
for these reactions to take place, the resulting effects are
analogous to those observed in animals that are naturally
capable of regeneration. That is, the activated
de-differentiated cells rapidly multiply to form a blastema
that is adequate for supporting regeneration of the missing or
injured tissues (skin, subcutaneous tissues, bone, and so
forth).

A major feature of the present invention is the
scaling of the applied voltage to the size of the wound.
Surprisingly, an approximately constant voltage on the order
of 0.1 V/in.sup.2 of wound area (about 0.0155 V/cm.sup.2) has
been found to be optimum for promoting healing and
regeneration of tissues while substantially avoiding the
deleterious effects associated with biological electrolysis
(to be described further below). Not only are specific
voltages in this range remarkably effective in stimulating
tissue healing and regeneration, but the electrically-injected
silver ions are extremely effective against a wide variety of
bacterial types (including gram positive, gram negative,
aerobic and anaerobic forms), fungi, and local viral
infections. Therefore, under optimal treatment conditions, the
electrically-injected silver ions are an extremely effective
agent against mixed infections and against many
antibiotic-resistant strains.

An important feature of the invention is the
anode, which is made of a material having a sufficiently high
silver content to supply the needed silver ions to the wound.
The anode is made of a flexible, silver-containing material
that is conformable to the wound surface, such as
silver-coated nylon fabric or the like. Materials usable with
the invention contain a sufficient quantity of silver to
produce an approximately constant current into the treated
area for at least several hours, preferably 12-24 hours or
thereabouts. Thus, silver-containing fabrics with a low
specific resistance are needed, preferably fabrics having a
specific resistance no greater than approximately 5
.OMEGA./cm, preferably no greater than approximately 1
.OMEGA./cm. Furthermore, fabrics with an approximately uniform
silver content (i.e., a uniform silver content per unit area)
that produce a uniform specific resistance throughout the
electrode are preferred. Other metals (gold, copper, zinc, and
so forth) may also be effective.

Another feature of the invention is the cathode,
which, like the anode, is made of a flexible,
electrically-conducting material, preferably a material having
a specific resistance no greater than approximately 500
.OMEGA./cm. By way of example, the cathode may be made of
carbon rubber or like materials.

Still another feature of the invention is the
placement of the cathode. For optimum results, the cathode is
placed so as to achieve an approximately uniform flow of
current through the treated region. In the human body, current
tends to follow the shortest path from the anode to the
cathode. Therefore, whenever possible, the cathode is
positioned on the opposing side of the extremity being treated
from the wound: for wounds on the palm of the hand, the
cathode is placed on the back of the hand; for wounds on the
dorsal surface of the forearm, the cathode is positioned on
the ventral surface, and so forth.

Another feature of the invention is the
silver-collagen complex, a specific physical association of
the electrically-injected silver ions with the collagen fibers
present in the wound area. While not wishing to be bound by
theory, it is believed that this complex generates a unique
localized electric field that activates embryonic cells in the
treated area, eventually leading to formation of an adequate
blastema to support regeneration.

Other features and advantages of the present
invention will be apparent to those skilled in the art from a
careful reading of the Detailed Description of a Preferred
Embodiment presented below and accompanied by the drawings.

**BRIEF DESCRIPTION OF THE DRAWINGS**

This application contains color drawings.

In the drawings,

**FIG. 1** is a flow chart showing three
sequential reaction processes resulting from the action of
electrically-injected silver ions;

![](fig1.jpg)

**FIG. 2** shows an electrical stimulation
device in use;   
    
 

![](fig2.jpg)

**FIG. 3** shows the preferred placement of the cathode for
optimum treatment according to the present invention;   
    
    
  


![](fig3.jpg)

**FIG. 4** is a partially cut-away view showing a
silver-containing anode placed on the surface of a wound;   
    
    
  


![](fig4.jpg)

**FIG. 5** is a plot of the current vs. time for a
silver-containing material usable with the present invention,
measured in vitro;

![](fig5.jpg)

**FIG. 6** is a flow chart illustrating
treatment according to a preferred embodiment of the present
invention;

![](fig6.jpg)

**FIG. 7a** is a photographic view showing a
wound on the foot of a 54-year-old male patient;

![](fig7a.jpg)

**FIGS. 7b, 7c, and 7d** are photographic
views showing the wound of FIG. 7a after thirty-one days, five
months, and seven months, respectively, of treatment according
to a preferred embodiment of the present invention;

![](fig7b.jpg)![](fig7c.jpg)

![](fig7d.jpg)

**FIG. 8a** is a photographic view showing
the middle finger of a 21-year-old male patient, after
traumatic amputation of one half the distal phalanx at the
level of the base of the nail;

![](fig8a.jpg)

**FIGS. 8b and 8c** are photographic views
showing the finger of FIG. 8a after 17 days and 38 days,
respectively, of treatment according to a preferred embodiment
of the present invention; and

![](fig8b.jpg)![](fig8c.jpg)

**FIG. 8d** is a photographic view of the
finger of FIG. 8a approximately 7 weeks after cessation of
treatment.   
    
 

![](fig8d.jpg)

**FIG. 8e** is a photographic view of the
finger of FIG. 8a approximately 7 weeks after cessation of
treatment.

![](fig8e.jpg)

**DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS**

In the following description, like reference
numerals refer to and identify the same structural elements,
portions or surfaces consistently throughout the drawings, as
such elements, portions or surfaces may be further described
or explained by the entire written specification. The terms
"proximal," "distal," "dorsal," "ventral," "volar,"
"opposing," "anterior" and "posterior" are used in the
customary anatomical sense. The "size" or "surface area" of a
wound or injury means the approximate surface area on a
macroscopic scale. The terms "scaled voltage" and "specific
voltage" refer to the voltage per unit surface area, for
example, V/cm.sup.2 or V/in.sup.2. Similarly, the term
"specific resistance" means the resistance per unit surface
area.

A number of critical factors have been
identified that are required for the successful use of silver
iontophoresis techniques to promote tissue healing and
regeneration. These factors are as follows:

1. There is a critical, previously unsuspected
relationship between the size of the wound and the optimum
magnitude of the voltage applied across the anode and the
cathode. Electrical injection of silver ions using an
approximately constant DC voltage scaled to the size of the
wound is surprisingly effective in promoting healing and
regrowth of injured and missing tissues. Treatment is
accomplished by placing a flexible, silver-containing anode in
contact with the open surface of the wound, placing a cathode
in contact with intact skin near the wound, and applying an
appropriate DC voltage, generally for at least approximately
24 hours.

2. The silver content of the anode should be
high enough to ensure a low specific resistance, preferably a
specific resistance no greater than approximately 5
.OMEGA./cm, more preferably no greater than approximately 1
.OMEGA./cm. Anodes with higher specific resistances may also
be useful for the practice of the invention however, the
optimum effect is achieved with low-resistance anodes. In
addition, the silver should be approximately uniformly
distributed (that is, the amount of silver per unit surface
area of the anode should be approximately uniform).

3. The cathode should be a flexible material
capable of making and maintaining a low resistance contact
with intact skin, so that the combined specific resistance
(i.e., cathode resistance and contact resistance) is no
greater than approximately 500 .OMEGA./cm.

4. The cathode should be positioned to maximize
current flow into the wound.

5. To maximize the input of silver ions into the
wound, the current should be maximized by minimizing the total
circuit resistance.

When these critical factors are present, an
unexpected phenomenon occurs: the input of sufficiently large
numbers of silver ions during a biologically appropriate time
frame (within 3-5 days) enables formation of a complex between
the silver ions and the collagen fibers in the wound. This
silver-collagen complex acts as a biological inducer to cause
the continual de-differentiation of fibroblast cells and the
continual multiplication of previously de-differentiated cells
in the area of the wound, leading to the accumulation of many
more embryonic cells in the area and, eventually, formation of
an adequate blastema to produce regeneration. These factors
will be discussed more fully below.

Scaling the applied DC voltage to the size of
the wound is crucial to successful treatment. The voltage
should be high enough to ensure an adequate input of silver
ions into the wound, but not so high that the deleterious
effects caused by biological electrolysis become evident.
"Biological electrolysis" or electrolysis in vivo differs from
electrolysis in vitro in the following respects: electrolysis
occurs in living tissues whenever there is current flow, no
matter how small. However, a wide variety of naturally
occurring agents act as buffers to prevent the accumulation of
potentially harmful electrolysis products. These products are
continually removed by blood and lymphatic circulation (which
also ensures a continual supply of fresh buffers), thereby
preventing a buildup of electrolysis products in the area. If
the critical voltage is exceeded, this natural buffering
action is rapidly overwhelmed and electrolysis products
accumulate with attendant pH shifts. This point defines the
onset of "biological electrolysis," which can be avoided by
taking the above-described critical values of voltage/area
into consideration.

Thus, selection of the appropriate treatment
voltage requires a knowledge of what happens in living tissue,
where the effects of electrolysis can be overcome by
circulation and buffering factors up to a point. The effects
of naturally-occurring buffers, blood circulation and lymph
circulation depend on the size of the wound. Thus, the results
of in vitro testing do not apply, nor do in vivo observations
of only one size of wound--each wound has its own maximal
voltage range which has to be clinically determined.

The critical specific voltage has been
determined to be approximately 0.09-0.11 V/in.sup.2 (about
1.4.times.10.sup.-2 -1.7.times.10.sup.-2 V/cm.sup.2),
preferably approximately 0.1 V/in.sup.2 (about
1.55.times.10.sup.-2 V/cm.sup.2). Not only are specific
voltages in this range surprisingly effective in promoting
tissue healing and regeneration, but the
electrically-generated silver ions are extremely effective
against a wide variety of bacterial types, including gram
positive, gram negative, aerobic and anaerobic forms. Similar
effects have been noted against a number of common fungi that
colonize open wounds, and may also occur in a number of local
viral infections (including herpes). Therefore, under optimal
treatment conditions, silver ions are an extremely effective
agent against mixed infections and against many bacteria that
have become antibiotic-resistant.

For any given size of wound, voltages lower than
optimum have no undesirable effects, but simply reduce the
efficacy of treatment in an approximately linear fashion due
to the production of fewer silver ions during any given period
of time, and more limited electrophoretic migration of those
ions into the tissues. At sufficiently low voltages, it is
simply not possible to supply enough silver ions in the time
frame required to produce the desired effects.

Higher voltages result in undesirable effects,
also in an approximately linear relationship to the applied
voltage. These effects range from irritation and slower
healing at modest overvoltages to localized pH alterations due
to accumulation of electrolysis products, cellular necrosis,
and actual increases in wound size at higher overvoltages. The
resulting buildup of dead tissue shields bacteria, fungi, etc.
in the region from the silver ion action and limits the
penetration depth of the ions.

Use of the appropriate anode material
contributes to a uniform current/voltage distribution over the
treatment area, together with a longer use time before the
onset of polarization. Preferably, the anode is made of a
flexible material with an approximately uniform silver
content, for example, flexible, silver-containing fabric. In
practice, the anode is replaced daily, thus, anode materials
which are capable of supplying a sufficient quantity of silver
ions for approximately 24 hours are preferred. Therefore, the
silver content of the anode is preferably sufficient to yield
a specific resistance no greater than about 1 .OMEGA./cm, as
noted above. Anodes with somewhat higher resistance (lower
silver content) may also be useful; however, these will be
exhausted in shorter periods of time, necessitating more
frequent replacement. Furthermore, higher-resistance anodes
may lead to non-linear voltages and thereby reduce the
efficacy of treatment.

The anode should also not only have a
sufficiently high content of silver (or other suitable metal;
see below), but the silver should be approximately uniformly
distributed. Non-uniform distribution means that the wound
will not be uniformly treated: some localized areas may be
subjected to significantly higher specific voltages that
others and the number of silver ions supplied to different
areas will differ. In some such instances, the local specific
voltage may be high enough to cause toxic effects.

It will be understood by those skilled in the
art that suitable anode materials may include those containing
silver alloys as well as substantially pure silver. Other
metals that produce the desired results may also be usable in
the practice of the invention, for example, gold, copper,
platinum, zinc, and so forth.

Suitable cathode materials include flexible
carbon rubber or the like (preferably containing the maximum
possible amount of carbon or graphite), or carbon-filled or
metal-containing fabric, having a specific resistance no
greater than approximately 500 .OMEGA./cm.

Optimum cathode placement is determined by
current flow in the human body. Current tends to follow the
shortest path from the anode to the cathode (i.e., the body
cannot be viewed as a single volume conductor). Therefore,
part or all of the wound will not be adequately treated if
cathode placement is nonoptimum. For example, for wounds on
the palm of the hand, placement of the cathode on the wrist
results in more silver ions being delivered to the proximal
portion of the wound and frequently an inadequate amount to
the distal portion. A more uniform distribution is achieved by
placing the cathode on the opposite side of the hand (the
dorsum), directly opposed to the palmar wound.

Optimal treatment according to the present
invention has as its aim the continuous introduction of the
largest possible population of silver ions into the wound
until healing or regeneration is complete, in a fashion that
does not introduce harmful by-products or produce deleterious
effects on the cellular processes. As noted above, the total
circuit resistance is minimized--and the current maximized--in
order to maximize the number of silver ions delivered to the
treatment site. The current may be monitored to ensure that
there are no high-resistance areas in the circuit (for
example, a dry treatment electrode, loose cathode, and so
forth).

When introduced into living tissues,
electrically generated silver ions undergo a series of three
reactions in a sequential fashion (FIG. 1):

In the first reaction, the silver ions combine
with proteins, peptides and other chemical species normally
present in solution in the tissues. Further chemical or
physiochemical combinations do not occur until all such simple
sites are completely filled. The first reaction typically
requires approximately 24 hours to go to completion (wherein
the term "completion" refers to saturation of available
sites). The antibacterial action of silver ions is a result of
this type of process, beginning at about 20-30 minutes
following exposure of the bacteria to the ions.

If more free silver ions are made available
following the first reaction, the second reaction occurs. The
second reaction is an association between the silver ions and
sensitive cells present in the wound, resulting in
de-differentiation of these cells into embryonic cell types
(as used herein, the term "sensitive cells" refers to cells
that are sensitive to free silver ions, including, among
others, mature fibroblast cells and epithelial cells). These
embryonic cells are not activated in the sense that they do
not multiply to produce additional cells of the same type;
however, they are capable of re-differentiation into other
cell types. Hence, these cells do not form an adequate
blastema mass to produce organized, multi-tissue regeneration.
Production of de-differentiated fibroblasts requires a
continuous supply of excess silver ions for at least
approximately 48-72 hours following saturation of the active
chemical sites in the first reaction ("excess" in this context
means that more silver ions are supplied than are needed to
combine with all available proteins, peptides, etc. in the
above-described first reaction).

If sufficient silver ions are made available
after the second reaction, a third reaction begins to take
place. The third reaction constitutes a specific physical
association of at least some of the silver ions with the
collagen fibers present in the wound to produce a unique
structure ("silver-collagen complex") having the specific
properties required to induce activation of the
de-differentiated fibroblast cells previously produced in the
second reaction.

Collagen fibers have size-specific sites which
are capable of forming a complex with hydrated metallic ions
(J. A. Spadaro, et al., "Size-Specific Metal Complexing Sites
in Native Collagen," Nature, Vol. 225, pp. 1134-1136 (1970)).
The copper/collagen complex, in particular, has a unique
electrical field which is involved in the initial epitaxial
deposition of bone mineral (apatite) on bone collagen (A. A.
Marino, et al., "Evidence of Epitaxy in the Formation of
Collagen and Apatite," Nature, Vol. 226, pp. 652-653 (1970)).
While not wishing to be bound by theory, it is believed that a
silver-collagen complex according to the present invention has
a unique local electrical field, and acts as a biological
inducer to activate the de-differentiated fibroblast cells
formed in the above-described second reaction. In mammalian
wounds (including human wounds) treated at appropriate
specific voltages with an excess of electrically generated
silver ions, the formation of this silver-collagen inducer
complex results in activation of the de-differentiated
embryonic cells formed by the action of the silver ions on the
pre-existing mature cells. Together, these effects result in
cell behavior and action akin to those observed in animals
that are capable of regeneration. In this fashion, an adequate
blastema to support regeneration is formed in human tissue.

The above-described factors are designed to
maximize the amount of silver ions introduced into the wound
during the window wherein the above-described reactions can
occur and lead to the formation of an adequate blastema for
regeneration--a necessary condition for completing the
sequence of three reactions within a biologically appropriate
time. Of these factors, the first (scaling the applied voltage
to the size of the wound) is believed to be crucial. If too
few silver ions are provided, healing simply proceeds
according to normal (i.e., nonregenerative) processes.
Lower-than-optimum voltages reduce the efficiency of the
treatment and lead to eventual failure of regenerative healing
(although healing by scarification and tissue replacement will
still occur). Higher-than-optimal voltages inhibit the third
reaction (formation of the silver/collagen complex) due to pH
shifts, accumulation of electrolysis products, tissue
necrosis, and expansion of wound size.

Referring now to FIG. 2, there is shown a
schematic view of an electrical stimulation device in use. A
device 10 includes a DC power source 12 with a positive
terminal 14 and a negative terminal 16. A treatment electrode
or anode 20 is placed in contact with the surface of a wound
to be treated, for example, a full-thickness defect 22 on the
palm of a patient P. Anode 20 is made of a flexible,
metal-containing material, preferably a flexible
metal-containing fabric such as silver-impregnated or
silver-coated nylon. Anode 20 may be covered by a "stent" of
gauze moistened with normal saline and a cover (such as
plastic film or like material), represented as 24. A return
electrode (cathode 26) is placed in contact with intact skin
near wound 22, for example, proximal to wound 22 as shown.
Anode 20 and cathode 26 are connected to power source 12 by
cables 30, 32, respectively. If desired, cathode 26 may be
incorporated into power source 20, for example, attached to
one side of the power source.

While treatment with the system shown in FIG. 2
may be helpful, current flow (and, therefore, the supply of
silver ions) to wound 22 is not optimized by the placement of
cathode 26. As described above, the preferred placement of
cathode 26 is one that results in an approximately uniform
distribution of current through the wound, thereby ensuring
approximately uniform delivery of silver ions thereto. Optimum
placement of cathode 26 is on the opposite side of the body
from the wound being treated, as illustrated in FIG. 3. For a
wound 22 on a surface 44 of the body (for example, the palm of
the hand), anode 20 is placed in contact with the wound, and
cathode 26 is placed on an opposite surface 46 (for example,
on the surface directly opposed to the palm). This placement
ensures an approximately uniform distribution of current flow
through wound 22, indicated schematically by arrows 48.

For optimum treatment, anode 20 substantially
engages a surface 38 of wound 22, as shown in FIGS. 3 and 4.
The presence of void spaces (even if filled with conducting
solution) results in inadequate treatment at those points.
Depending on the extent of wound 22, anode 20 may be in
contact with exposed subcutaneous tissues 42 as well as dermal
tissue 40 at the margins of the wound. Thus, the material of
anode 20 needs to be sufficiently flexible to conform to
surface 38. As shown in FIG. 4, anode 20 is dimensioned to
just cover wound 20, that is, anode 20 has a slightly larger
surface area than the area of wound surface 38.

As described above, anode 20 contains a
sufficient quantity of silver so that, when device 10 is
connected for use as shown in FIG. 2, the current density
delivered to wound 22 is approximately constant for a period
of several hours, preferably at least approximately 24 hours.
By "approximately constant current" is meant a DC current that
may increase to a peak 50 immediately after the onset of
treatment, but that decreases within several hours to an
approximately constant level 52 and maintains that level until
the onset of polarization at 54 (FIG. 5). FIG. 5 shows the
current vs. time in vitro for a 25 cm.sup.2 section of a
silver-coated nylon fabric usable with the invention, applied
to a block of gelatin prepared with physiological saline. A
standard return electrode was applied to the opposite face of
the block and a voltage of 0.42 V applied between the two
electrodes. The current density at peak 50 was approximately
3.5 .mu.A/cm.sup.2, decreased to approximately 1.5
.mu.A/cm.sup.2 within 5 hours, and remained at that level
until the onset of polarization approximately 20 hours later.

A flow chart illustrating treatment according to
the present invention is shown in FIG. 6. Patients are treated
as soon as possible following the injury, preferably
immediately following cleaning and debridement (if needed) of
the wound. However, treatment may be initiated at any time
thereafter, or whenever deemed medically necessary. The
treatment electrode (anode 20) is applied directly to the
surface of the wound, moistened with physiological saline or
other suitable liquid, covered, and connected to the positive
terminal of a low-voltage DC power source (such as source 12).
The return electrode (cathode 26) is placed on intact skin
near the wound (on an opposing surface whenever possible) and
connected to the negative terminal of the source. Then, a low
intensity DC voltage and current are applied continuously for
a period of at least approximately 24 hours. The wound is
inspected and cleaned daily, and anode 20 is replaced at that
time. Cathode 26 is inspected daily and changed as needed.

Liquids suitable for use with the invention
include electrically conducting liquids such as normal saline
(also known as isotonic saline or physiological saline),
Ringer's solution, wound exudate and other body fluids found
in the area of the wound, and mixtures and dilutions thereof.
Tap water may also be useful; however, the composition of tap
water is so variable that other electrically-conducting
liquids are preferred. The terms "normal saline," "isotonic
saline" and "physiological saline" refer to a solution of
sodium chloride (NaCI) in purified water (H.sub.2 O),
containing approximately 0.9 gram of sodium chloride per 100
milliliters of water. Such a solution is approximately
isotonic (i.e., has the same osmotic pressure) with body
fluids. The term "Ringer's solution" means a solution of about
0.86 gram sodium chloride (NaCI), 0.03 gram potassium chloride
(KCl), and 0.033 gram calcium chloride (CaCl) in purified
water. The term "wound exudate" refers to any substance that
is exuded from a wound, including materials that pass through
the walls of blood vessel walls into the surrounding tissues.

The key element in promoting healing and
regeneration according to the present invention is the
production of de-differentiated cells in the region of the
wound, which in turn depends on the above-described critical
factors. The voltage applied across the treatment (anode 20)
and return (cathode 26) electrodes must be wound-specific,
that is, proportional to the size of the wound (preferably,
approximately 0.1 V/in.sup.2); the anode must have an
approximately uniform silver content that is sufficiently high
to ensure a specific resistance no greater than approximately
1 .OMEGA./cm; the cathode must be made of a suitable
low-resistance material capable of making and maintaining a
low resistance contact with intact skin; the cathode is
positioned so as to maximize current flow into the wound
insofar as practicable; the total circuit resistance is as low
as possible. In all instances, the treatment electrode is
configured so as to yield an approximately uniform voltage
distribution throughout the area of the wound.

Scaling the voltage to the size of the wound is
particularly important in the case of larger wounds (that is,
wounds with surface areas greater than approximately 8-10
in.sup.2 (about 50-65 cm.sup.2), where a naonuniform voltage
distribution through anode 20 may result in the production of
electrolysis effects in localized "hot spots."

In all cases, the total voltage applied across
anode 20 and cathode 26 is preferably no greater than about
0.9-1.1 V. The the area of anode 20--and the size of a wound
treated therewith--is therefore limited to approximately 9-11
in.sup.2 (about 60-70 cm.sup.2). For larger wounds, two or
more devices 10, each with its own anode, cathode, etc. are
used, thereby ensuring that no single anode-cathode pair has
an applied voltage greater than the preferred maximum. Thus,
power source 12 may have several output voltages, each with a
corresponding output terminal (for example, 0.1 V, 0.2 V, and
so forth) for treatment of wounds of the corresponding size.
Anodes 20 for use with such a power source have terminals that
allow them to be connected only to the output terminal with
the correct output voltage: a 1"-square anode to the 0.1V
terminal, a 2"-square anode with the 0.2V terminal, and so
forth.

During treatment, silver ions from anode 20
migrate into the tissues surrounding wound 20, where the ions
undergo the three reactions shown in FIG. 1: binding to
proteins, peptides, etc. in the area; de-differentiation of
normal cells (primarily fibroblasts) into primitive,
de-differentiated cells, and binding to collagen fibers to
form a silver-collagen composition that in turn activates the
de-differentiated cells. The activated cells multiply rapidly
and re-differentiate to form the specific types of normal
mammalian cells needed to restore the region to its pre-injury
state (dermal and epidermal tissue, muscle tissue, nerve
tissue, blood vessels, bone cells, and so forth, as may be
needed for the particular site being treated).

As noted above, silver compounds such as
AgNO.sub.3 have long been known to possess bactericidal and
fungicidal properties; however, compounds of the higher
oxidation states of silver (Ag(II) and Ag(III)) have recently
been found to be significantly more effective than monovalent
(Ag(I)) compounds (M. S. Antelman, "Silver (II,III)
Disinfectants," Soap/Cosmetics/Chemical Specialties, March,
1994, pp. 52-59). While not wishing to be bound by theory, it
is thought that the superior bactericidal and fungicidal
effects of electrically-generated silver ions may be due at
least in part to the formation of free silver ions of these
higher oxidation states and their action on bacteria, fungi,
etc. present in the tissues.

It is believed that the silver-collagen complex
formed at the treatment site results from a specific
attachment of silver ions to collagen fibers, resulting in the
formation of electrically active sites which act as biological
inducers to activate the de-differentiated fibroblast cells.
The complex may also have a de-differentiating effect on at
least some of the remaining silver-sensitive cells in the
area, but without requiring the direct attachment of the
silver ion to the cell membrane as in the second reaction
(FIG. 1). Thus, optimum treatment conditions result in a
greater immediate effect on the cellular components in the
wound area than do silver ions alone, since a much greater
number of active de-differentiated cells are produced than
would result solely from the direct action of
electrically-introduced silver ions on the fibroblast cells.
The complex also permits the expression of additional long
term healing and maturational effects after active silver
treatment is terminated, as will be described further below.

The silver-collagen complex may be prepared in
vitro by application of low-voltage DC current from a silver
anode to a collagen-containing substrate, then formed into
suitable shapes (rolls, sheets, etc.) for external application
to surface wounds or internal application to body parts (if
desired, the complex may be incorporated into a wound
dressing). The complex may act to produce de-differentiation
of mature, sensitive cells; alternatively it may activate
previously de-differentiated cells in the area. For
applications where there are insufficient numbers of mature
fibroblast cells present, the complex may be infiltrated with
de-differentiated cells produced by the above-described
technique in order to provide a source of de-differentiated
cells to start the in vivo induction process.

The present invention is further illustrated in
the following nonlimiting examples.

**EXAMPLE 1**

Portions of granulation tissue ranging in size
from approximately 1-2 mm were removed from optimally treated
wounds and explanted into an appropriate tissue culture
medium, resulting in the formation of large numbers of new
cells in the culture medium. The new cells were embryonic in
nature and formed in contact with the explants, multiplying
rapidly and spreading out from the explants until
approximately 3/4 of the culture dish was covered with
embryonic cells. New cell formation ceased after 3-4 weeks,
and all the cells then present reverted to normal fibroblast
morphology. No further cell multiplication occurred.

**EXAMPLE 2**

Explants of granulation tissue were cultured as
described in Example 1; however, the original explants were
removed from the culture medium before cessation of new cell
formation. All new cell production ceased after removal of the
explants from the culture medium. Histological analysis
revealed that the explants removed from the culture medium
were composed solely of collagen fibers.

**EXAMPLE 3**

Explants of granulation tissue were cultured as
described in Example 1. The explants were removed from the
culture medium at approximately 1-week intervals, placed in
sterile saline and refrigerated for 3-5 days. All new cell
production ceased after removal of the explants from the
culture medium; cell production resumed after the explants
were re-implanted in the medium.

**EXAMPLE 4**

Granulation tissue from a wound treated with a
specific voltage greater than the above-described optimum was
explanted into a suitable tissue culture medium. No new cell
production was observed, regardless of the length of time the
culture was maintained.

**EXAMPLE 5**

Granulation tissue from an optimally treated
wound was maintained in tissue culture until the cessation of
new cell formation, but before reversion of the embryonic
cells to mature fibroblasts. The explanted granulation tissue
was removed, injected with silver ions for approximately two
hours, and then re-implanted into the original culture medium
at its original site. New cell production resumed.

**EXAMPLE 6**

Gelatin blocks were prepared from commercial
collagen product in a normal saline solution. After hardening,
the blocks were subjected to appropriate levels of DC voltage
from a silver anode for 12 hours. After cessation of
electrical treatment and removal of the anode, the blocks
demonstrated a voltage and current production only slightly
lower than that administered for an additional 10-12 hours.

While the exact structure of the silver-collagen
complex has not been determined, Examples 1-6 indicate the
production of such a complex under the appropriate conditions
(i.e., when wounds are treated with the optimum specific
voltage). The complex does not form when wounds are subject to
higher voltages.

**EXAMPLE 7**

Volunteer patients were treated for a wide
variety of traumatic wounds using the above-described
methodology, including wounds to the extremities which may
heal with difficulty due to poor natural healing processes.
Each patient was advised of the experimental nature of the
treatment and was offered conventional treatment; each patient
who selected the experimental treatment was free to
discontinue it at any time. Treated wounds included burns,
lacerations, crush injuries, amputations, and infections.
Patients ranged in age from 2.5 years to 81 years.

Patients were treated as soon as possible
following the trauma. Debridement, if needed, was done under
anesthesia. Silver ions were introduced directly into the
wound by means of a small electrical current from a
silver-containing nylon anode as described above. The
treatment electrode (anode 20) was cut to approximately fit
the wound, wetted with tap water and/or normal saline, and
applied directly to the wound. The electrode was then covered
with a small flexible, carbon-rubber electrode with an
integral, thin, flexible wire that was connected to the anode
of a DC power source. The wound was then wrapped in a soft
dressing with a water-impermeable layer to prevent the
dressing from drying out.

The return electrode (cathode 26) was placed on
the opposing side of the limb from the wound as indicated in
FIG. 3. Where this placement was not feasible (for example,
fingertip injuries), the return electrode was placed proximal
to the wound as shown in FIG. 2. The power source was a
voltage-controlled, battery operated solid state unit set to
deliver a constant, direct current voltage.

Most patients were treated on an outpatient
basis after the patient and his/her family members were
instructed in the techniques of electrode preparation and
application. Treatment was continuous; the anode was changed
daily with no special sterile precautions. The cathode was
removed daily, cleaned with tap water and reapplied to the
original site. All patients continued their daily dressing
changes at home with weekly follow-up visits; all reported
minimal difficulty or pain associated with the dressing
changes. Patients with obviously contaminated wounds were
given systemic antibiotics for the initial three days of
treatment to prevent systemic infection (for example,
infection resulting from any initial surgical debridement). No
infections occurred in the entire series; all pre-existing
infections cleared rapidly (within 3-4 days). Patient
compliance was excellent, and treatment was terminated when a
satisfactory clinical result was achieved.

A total of 24 wounds were treated, including
bums, lacerations, crush injuries, open fractures,
amputations, and infections. All wounds involved soft tissue
loss with full thickness skin loss ranging in area from 1
cm.sup.2 to 18 cm.sup.2 with an average of about 4 cm.sup.2.
Treatment voltages ranged from about 0.3 V to about 0.9 V,
depending on the surface area of the wound. Current densities
ranged from approximately 4-8 .mu.A/cm.sup.2, with the
magnitude of the current in individual cases being dependent
upon the surface area of the wound. Treatment times ranged
from 7 to 72 days, with an average of 30 days; follow-up times
ranged from 2 to 22 months with an average of 10 months.

All patients regained their preinjury activity
level; all patients with occupational injuries returned to
their original or equivalent occupations. Despite the lack of
sterile precautions, there were no infections (in one case, a
pre-existing post-operative infection was well treated with
the silver ions alone).

In all cases, full thickness skin loss was
replaced with normal-appearing, full thickness, flexible skin
appropriate to the area, with regrowth of subdermal tissues
and minimal or no scarification. Initially, the skin appeared
to be full-thickness, flexible and innervated; however, it was
darker than normal and underwent a subsequent maturation
period of several months before gradually acquiring a more
normal coloration, dermatoglyphic pattern, and hair growth (in
appropriate regions). The normal dermatoglyphic pattern on
volar skin areas became more evident with the passage of
additional time following treatment. Skin areas were sensitive
to light touch, and almost all patients reported the sensation
in the area to be subjectively normal without paresthesias,
numbness or cold intolerance; only three patients had less
than fully normal sensation. Typical results were as follows:

Patient 1. An 11-year-old female lacerated the
radial aspect of the left thumb, incurring a full-thickness
skin loss of approximately 2 cm.sup.2 in area extending from
the midpoint of the nail to the mid IP joint and centered over
the neutral line between dorsal and volar skin. Treatment
using an appropriate voltage was instituted on the day of
injury and continued for 28 days.

At the conclusion of treatment, the wound was
completely healed with apparently full-thickness skin of a
darker than normal coloration, and with good sensation. Normal
dorsal-type skin was regenerated dorsal to the neutral line;
normal volar skin was formed volar to the neutral line.
Coloration and sensation returned to normal over the next
month, accompanied by a full range of motion at the IP joint.
Thirteen months post-injury, there was no scarring or
contracture; sensation was completely normal and the area of
the original injury could not be discerned.

Patient 2. A 28-year-old male incurred multiple
longitudinal lacerations of the distal phalanx, middle finger
right hand, in an industrial accident. On admission, the
finger tip was noted to be "filleted" with three deep
longitudinal lacerations extending from the dorsal to the
palmar surface and proximally into the nail bed with total
avulsion of the nail and exposure of the terminal phalanx. The
skin over the central portion was insensate.

The wound was immediately irrigated, the various
parts loosely approximated with an absorbable suture and
dressed with silver-containing nylon fabric, and treated with
an appropriate voltage. Antibiotics were given for 3 days
starting immediately post-operative. Seven days after start of
treatment, there was evident healing of the laceration;
treatment was terminated 20 days later. At that time, the skin
was almost completely healed, there was a normal contour to
the finger tip and sensation was present in the central
portion of the wound. Two months after injury, there was
minimal scarring on the distal pad, a normal appearing nail
was approximately 50% regrown, and normal sensation and range
of motion were present. At 12 months follow-up, the finger was
asymptomatic, normal in appearance, and fully innervated with
normal sensation.

Patient 3. A 33-year-old male utility worker
contacted a 7,200-volt electrical line through both hands. He
was unconscious for several minutes and incurred bums of the
right hypothenar eminence and dorsum of the left hand at the
MCP joint line. The hypothenar burn extended from just distal
to the 5th MP joint to the base of the 5th metacarpal and
consisted of three confluent, ovoid areas of full-thickness
skin loss, with a total area of approximately 12 cm.sup.2.
These areas were blanched and without sensation. The extent of
subcutaneous necrosis could not be estimated. The dorsal bum
of the left hand involved the second through the fifth MCP
joint dorsal surface with full-thickness skin loss over the
protuberant areas totaling approximately 4 cm.sup.2.

Treatment was begun to both hands on the 4th day
after injury, and continued for 16 days on the left hand and
32 days on the right hand. At the end of the treatment, the
wounds on the dorsum of the left hand were epithelialized with
full-thickenss, flexible skin with good sensation and normal
range of motion in the MCP joints. The distal half of the
hypothenar wound on the right hand was re-epithelialized with
full-thickness sensate skin. The proximate half of the wound
was normal in contour and covered with full-thickness skin
except for an approximately 1 cm.sup.2 area in the center
which was covered with thinner skin. Six months after injury,
the hypothenar burned area of the right hand was fully
innervated and flexible with a normal range of motion of the
MCP of the little finger. At that time, the skin was beginning
to acquire a normal color and dermatoglyphic pattern.

Patient 4. A 54-year-old male injured his left
foot in a lawnmower accident, resulting in extensive soft
tissue injury and open fractures of the 3rd, 4th, and 5th
metatarsals and cuboid bone. He underwent debridement and
stabilization on the day of the accident. Further debridement
was done on the 3rd, 4th, 5th and 23rd days after the
accident. Due to the amount of soft tissue loss and bone
injury (FIG. 7a), the patient was scheduled for a vascularized
composite graft to the injured area. He was given a 50% chance
of success, and was advised that the foot might have to be
amputated if the surgery failed.

Treatment was initiated on the 32nd day after
injury; the patient was placed on oral antibiotics for four
weeks. Seventeen days after the start of treatment, the wound
was debrided, a portion of avascular bone was removed, and two
pins that were projecting into the open wound were removed.

Thirty-one days after the start of treatment,
the gross infection had resolved and the wound was closing
very well (FIG. 7b). Over the next four months the wound
closed to a small opening (FIG. 7c). At that time, it was felt
that an underlying osteomyelitis precluded complete closure of
the opening. Therefore, the bone was debrided under local
anesthesia and treatment continued. The wound was completely
closed and healed within two months thereafter (FIG. 7d). The
patient has continued to do well; he has regained an excellent
range of motion of the foot with a normal gait pattern.

Patient 5. A 21-year-old male caught the middle
finger of his right hand in a metal press, and lost the distal
one-half of the distal phalanx of the middle finger at the
level of the base of the nail. Treatment according to the
present invention was initiated immediately upon presentation,
without wound debridement. After 2 days, the patient was pain
free and able to change the dressings by himself. Seventeen
days after treatment was initiated, regeneration of bone and
soft tissue was apparent (FIG. 8b). Thirty-eight days
afterwards, the distal phalanx was fully restored with
organized, multitissue structure; regeneration of appropriate
tissues (skin, muscle, nail, etc.) was underway. Treatment was
discontinued at this time.

Seven weeks after cessation of treatment, the
nail was almost completely restored and the volar surface of
the finger tip had a normal dermatoglyphic pattern (FIG. 8e).
The patient had a full range of motion of the finger and
normal sensation of the finger tip, with no permanent physical
impairment.

Scaling the treatment voltage to the size of the
wound, in conjunction with the other above-identified factors,
allows the entry of sufficient numbers of free silver ions
into the wound to optimize healing and, in appropriate cases,
induce regeneration of missing tissues. It is believed that
the observed results were largely due to the action of the
silver-collagen complex which produced a large volume of
de-differentiated cells in the treatment region. The residual
silver-collagen composition in the area is believed to be
responsible for the observed long-term continuation of the
healing and maturational process after cessation of active
treatment, eventually resulting in the restoration of
substantially normal function.

It will be apparent to those skilled in the art
that many changes and substitutions can be made to the
preferred embodiment herein described without departing from
the spirit and scope of the present invention as defined by
the appended claims.

---

[**http://www.silvermedicine.org/robertobecker.html**](http://www.silvermedicine.org/robertobecker.html)
  
**( For more information: <http://www.silvermedicine.org/silveriondeliver.html>
~ <http://www.silvermedicine.org/attributesofsilverparticlesandsolutions.html>
)**

**"Robert O. Becker - The Discovery of
Silver"**

Dr. Becker first used silver in 1971. His
experiments at this time focused on proving that minute
amounts of electrical current could dedifferentiate cells and
stimulate limb regeneration in rats. For his experiments, Dr.
Becker elected to use a platinum electrode as the negative
pole ( cathode ) and a pure silver electrode as the positive
pole ( anode ) with a 106 - 108 Megohms resistor wired into
the circuit. He implanted the device in 35 rats, and achieved
the most notable results using 1 nanoamp of current.

In 1972, Dr. Becker was ready to begin
experimentation with electrical stimulation for bone growth in
humans, particularly in cases where broken bones ( nonunions )
refused to heal. Again, Dr. Becker chose to use silver,
primarily because he believed silver was less likely to
chemically react with tissues and he believed that silver
would transmit the electrical current most efficiently.

Testing conducted by Dr. Becker's team
demonstrated that the positive pole of a silver electrode in a
low current circuit would kill all forms bacteria within a 1/2
inch radius. Dr. Becker hypothesized that this effect was due
to the delivery of silver ions directly into the adjacent
tissues. Never-the-less, his primary concern was that the
positive current at the treatment site might cause delays in
healing. Up to this point, research indicated that growth
stimulation occurred at the negative electrode.

Dr. Becker eventually concluded that while all
five of metals they tested stopped growth of all bacteria, the
current required for all types except silver required
dangerously high levels of current. Dr. Becker hypothesized
that the other metals killed bacteria by poisoning the
bacteria and normal cells. Eventually, Dr. Becker confirmed
that the silver deactivated or killed all bacteria with no
side effects with small ( and safe ) levels of current.

Dr. Becker eventually began experimenting with
silver-impregnated nylon as a form of wound dressing designed
to kill bacteria; he continued to use "positive current" to
kill bacteria and "negative current" to stimulate tissue/bone
growth. Becker's team commonly used between 100 to 200
nanoamps of electrical current per centimeter of electrode in
their research. Dr. Becker concluded that other researchers
were using far too much current in related experimentation,
and that electricity exceeding one volt posed the possibility
of dangerous side effects in nearby tissues.

In 1977, Becker first noticed that the silver
anode ( positive pole ) appeared to actually be stimulating
bone growth as well as eliminating infections. By 1978 he had
repeated this phenomenon a number of times, and decided to
reevaluate the theory that only the negative current
stimulated tissue growth.

In 1980 Dr. Becker, through extensive research
and experimentation, concluded that the current was not the
determining factor with this stimulated growth. Rather, it was
the silver ions that were responsible for the accelerated
healing at the anode. He found that cells within 5 millimeters
of the silver were actually altered. In cultures, Dr. Becker
demonstrated that silver ions effected cell changes to the
extent that the cells grew extremely quickly, producing
primitively formed cells including fully dedifferentiated
cells and rounded fibroblasts. Furthermore, the process of
using silver ions to stimulate healing resulted in a 50%
reduction in the healing time.

While it is universally accepted by
knowledgeable researchers that silver ions can, in fact, alter
cell morphology, some dispute the claim that actual cell
dedifferentiation occurs. However, these conflicting findings
may be due solely to the actual amount of current used;
increased levels of current may in fact interfere with the
process. Dr. Becker is virtually alone in the belief that the
amount of current used should be minute, approaching the same
levels of the natural DC current present in the human body.

Before Becker's research group dissolved, Dr.
Becker found that silver ions, electrically injected, could
suspend the mitosis of ( cancerous ) malignant fibrosarcoma
cells. Dr. Becker hypothesized that cancer cells, regardless
of the initial cause, were cells caught in a partially
differentiated and primitive state. However, this promising
research was never fully explored.

Dr. Becker's conclusion was that low-current
silver electrodes stimulate bone formation by
dedifferentiating cells and possibly stimulating periosteal
cells. Dr. Becker's greatest cautionary note is the
observation that high levels of current will stimulate cancer
cell growth; the key is low-current with pure silver
electrodes.

**Research Points of Interest**

Red blood cells of a frog can be
dedifferentiated by using extremely small amounts of current,
measured in billionths of amperes.   
Bone growth stimulation occurred with platinum electrodes ( at
the negative electrode ) at a maximum of 3 micro amps (
generated by a power source delivering an initial 100 micro
amperes )   
The average amount of voltage required to induce electrolysis
in human tissues was 1.1 volts of direct current ( any amount
of current above this point can cause cell damage or cell
death )   
Becker's group demonstrated that by using silver electrodes
and 0.1 micro amperes of current, bone growth stimulation
still occurred, and nonunion fractures healed.   
Dr. Becker noted that cancer cell growth was stimulated by
300% using the 10 microampere method.   
Dr. Becker noted that the combined effect of the proper level
of current and the delivery of silver ions could
dedifferentiate cancer cells; both elements must be correctly
applied for any results ( the activation of primitive-type
genes in a cell nucleus ).   
Dr. Becker realized that the silver electrode method could be
used on a patient's cells, and that large quantities of
primitive cells could be stored for use at later date.

In January of 1980, primarily due to political
reasons, the inflow of research grant money stopped, and Dr.
Becker was forced to close his laboratory, even though he was
likely on the verge of incredible breakthroughs in full tissue
and organ regeneration in humans.

---

![](silvrelctrolys.jpg)

**( http://www.silvermedicine.org/robertobecker.html )**

---

[**http://www.all-natural.com/silver-1.html**](http://www.all-natural.com/silver-1.html)

**Colloidal Silver --- The Rediscovery
of a Super Antibiotic?**

(Excerpt)

Dr. Robert Becker, " The Body Electric,"
recognized a correlation between low silver levels and
sickness. He said the silver deficiency was responsible for
the improper functioning of the immune system. Dr. Becker's
experiments conclude that silver works on the full spectrum of
pathogens without any side effects or damage to any part of
the body. He also states that the silver was doing something
more than killing disease organisms. It was also causing major
growth stimulation of injured tissues. Burn patients and
elderly patients noticed more rapid healing. He discovered
that all cancer cells change back to normal cells. All strains
of pathogens resistant to other antibiotics are killed by
colloidal silver. Yet at that time he couldn't find a silver
supplement on the market.

---

[**http://www.molluscum.com/why\_silver.php**](http://www.molluscum.com/why_silver.php)

**A Short History of the Use of Silver
in Medicine**   
( Excerpt )

A project begun at the State University of New
York by Robert Becker and associates involved a silver nylon
product in the early 1970s. This project was originally
instigated in order to find an electromagnetic shield.
Instead, it lead to the revolutionary discoveries by Becker of
silvers unique antimicrobial properties, and his discovery
that silver ions could induce fibrocytes to dedifferentiate
into stem cells and back again. One of Beckers research
associates, A. Bart Flick, continued work in this area for
professional and commercial applications. As a result, Flick
has filed patents in 1994, 1996 and 2000 for silver-based
wound dressings that are far superior to anything that has
ever been available before. He has also obtained approval for
these dressing from the US Food and Drug Administration.
Because of the success of these silver dressings, many other
medical product manufacturers have filed for their own
parallel products...

---

[**http://www.perutechnologies.com/sipr2.html**](http://www.perutechnologies.com/sipr2.html)

**Silver Helps Regrow Human Tissue 
Physician Patents Technique Using Silver Ions**

by **Mike DiRienzo**

The Silver Institute, Washington DC   
July 27, 1999

*Washington, D.C.*  Silver, the same
commodity used in coins and in the manufacture of jewelry,
silverware, mirrors and electronics, helps regenerate human
cells that have been destroyed by disease or damaged in
accidents, according to a recently released report in this
month's edition of Silver News, a bi-monthly newsletter
published by The Silver Institute.

Clinical tests indicate that the silver-based
procedure is so successful that one patient who had sustained
three crushed fingers in an accident grew new tissue rapidly.
Within 2-1/2 months, skin coverage was complete and there was
normal full sensation, good blood supply and all joints had a
normal range of motion. If left untreated, the 30-year old
electrician's fingers would have fallen off after turning
black from gangrene, and he would have been left with a
totally useless hand. Ironically, his orthopedic surgeon
recommended amputation of all three fingers, but the patient
requested silver-ion therapy which proved successful.

The mechanism by which silver ions help rebuild
tissue has been studied for more than a decade by Dr. Robert
Becker of Becker Biomagnetics in New York. Dr. Becker
initially reported his findings at the First International
Conference on Silver and Gold in Medicine, co-sponsored by The
Silver Institute in 1987. In the decade since, this technique
has been used in clinical settings where hundreds of patients
with various wounds have recovered. In addition, a laboratory
study conducted by the U.S. Army Institute for Surgical
Research in Houston, Texas, showed that laboratory animals
with burn wounds treated under controlled conditions
experienced shortened time for reconstruction with
silver-nylon dressings. Recovery of skin function was faster
when electric current was applied compared to no application
of electric current. Last fall, Dr. Becker received a U.S.
patent (5,814,094) for the devices, materials, and techniques
involved in regeneration of tissue using silver ions.

After several hundred cases, Dr. Becker believes
that the technique works in three stages. The first stage is
the chemical combination of highly active free silver ions
with all bacteria or fungi present in the wound which are
inactivated within 20 to 30 minutes. The second stage occurs
over the next few days. Silver acts on fibroblast cells to
cause them to revert to their embryonic state, becoming stem
cells. These cells are universal building blocks whose role is
to reconstruct new tissue. In the final stage, silver ions
form a complex with the living cells in the wound area to
produce immediately convertible stem cells. The end result of
this conversion is that the stem cells supply all the building
blocks necessary to completely restore all anatomical
structures.

No other known treatment provides sufficient
numbers of the embryonic or stem cells required for true
regeneration of damaged or destroyed tissues in humans and
animals. The success indicates that there is the potential not
only for the healing of near-surface wounds, but for
regenerative repair of internal organs such as the heart,
liver, brain and the spinal cord.

*For Further Information Contact*: Mike
DiRienzo, The Silver Institute 1112 16th Street, N.W., Suite
240 Washington, D.C. 20036 Tel: (202) 835-0185 Fax: (202)
835-0155   
Copyright (c) 2000 The Silver Institute All Rights Reserved

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![](becker.jpg)

**Dr Robert O. Becker**

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