Global Innovation in Wound Care Summit Series - What Do I Need to Know About Skin Substitutes by woundmasterclass

December 2023

Global Innovation in Wound Care Summit Series What Do I Need to Know About Skin Substitutes? Moderator Miss Negin Shamsian Consultant Plastic and Reconstructive Surgeon (Locum) London, United Kingdom

requirements. Surgery and secondary healing is good, when a combined approach can occur, but the key question is when to use what. Dr N. Shamsian precedes to ask, ‘What is the most common type of wound you see?’, to which Devine responds that it is mostly chronic wounds; venous

Introduction

ulcers, lower extremity wounds, and sometimes

surgery from previous cancer treatment. The use r N. Shamsian is joined by North American

of skin substitution is vital as it can prevent further

expert Dr J. Lantis (Professor and Chief in

arduous surgical management and gives the clinician

Surgery), Associate Professor M. Wagstaff

options for preservation and treatment.

(Head of Plastics and Reconstructive Unit, Australia) and Dr M. Devine from Arizona (Plastics and

“How has microsurgical transfer to skin substitutes

Reconstructive Surgeon).

changed over the last 2 decades?”

Global expert

Due to the variety of options available for skin substitution, there is a lesser need for surgical

Dr Michael N. Desvigne

transfer, but rather more additional scaffolding with

Board-Certified Plastic Surgeon, General Surgeon, Hyperbaric physician, Wound Care Clinician

skin substitutes and the advantage of synergistic

Scottsdale AZ, United States

of experience, or expertise, is within the field of

substitution. Devine explains that his primary area placental-type products.

Supported by

The Use of Aseptically Processed Placental Allograft

Processing the material matters as you can achieve

and Meshed Reticular Acellular Dermal Matrix in

the same sterility as terminally sterilized tissue

Soft Tissue Reconstruction

which preserves tissue structure, matrix proteins and signaling cues. This provides a safe, quality

Dr M. Devine hosts the next segment of wound

tissue that is most like native autograft (human skin).

management as a Plastics and Reconstructive

Terminal sterilization alters tissue properties of the

surgeon based in Arizona. Devine notes that there are

native tissue by denaturing the structure and matrix

a lot of options for skin substitutes, and it depends

proteins, with a compromised binding site for cell

on the goal and customized approach of the patients’

attachment and signaling functions.

Wound Masterclass - Vol 2 - December 2023

Global Innovation in Wound Care Summit Series: What Do I Need to Know About Skin Substitutes?

“The meshed HR-ADM had properties that allowed for tissue integration and incorporation with the soft tissue deficits benefitting particularly from the processed placental allograft.”

aseptically processed allograft included proliferation, We must consider an algorithmic approach to

angiogenic, and antimicrobial properties that were

placental allografts.

useful for wound healing and surgical reconstruction. The meshed HR-ADM had properties that allowed

•

Wound management; Cellular proliferation –

for tissue integration and incorporation with the

AmnioBand Membrane. Dermal replacement –

soft tissue deficits benefitting particularly from the

AlloPatch Pliable

processed placental allograft. The use of HR-ADM may aid in creating a scaffolding for tissue ingrowth,

•

Incisional management; Cellular proliferation –

later supporting flap transfer, as well as adequate soft

Salera mini membrane placental Allograft

tissue coverage.

Anticipating post-surgical complications; cellular

Global expert

proliferation – Salera mini membrane placental

Prof Marcus Wagstaff

Allograft. Dermal replacement and/or soft tissue

Plastic and Reconstructive Surgeon, Head of Unit of the Adult Burns Service at the Royal Adelaide Hospital (RAH)

scaffolding – SomaGen Meshed dermal matrix •

Optimizing

surgical

outcomes;

Adelaide, Australia

Cellular

proliferation – Salera mini membrane placental allograft. Dermal replacement and/or soft tissue scaffolding – SomaGen Meshed dermal matrix

NovoSorb BTM - Biodegradable Temporising Matrix

Some of the key benefits to Somagen is that it is the

In this next segment of wound management and

first of its kind (meshed reticular dermal allograft), is

skin substitution methods, we go to Prof M Wagstaff

ready to use that saves valuable operating theatre

(Associate and Desvigne Professor in Plastic Surgery,

time, pliable and conforms to anatomy, compatible

and the Head of Burns Unit Royal Adelaide Hospital,

with advanced wound care such as NPWT, it has

Australia). When BTM was being developed in 2011,

a versatile meshing ratio which allows clinicians

Wagstaff was part of the research team and overlooked

to address wounds on a much larger scale, and an

the first clinical trials with human patients, further

18-month shelf life at room temperature.

developing the products based on their findings and research. Synthetic skin substitutes include a variety

Case

Summary;

Multiple

pressure

ulcers.

of temporary and permanent examples, and the

y/o paraplegia secondary to transverse myelitis

ones we tend to think of are Bio-Brane (for epithelial

secondary to COVID. This patient developed multiple

coverage of superficial burns to prevent water loss),

pressure ulcers during prolonged hospitalization

and dermal substitutes that are a permanent implant

which progressed to the bone. The patient was

(BTM). Biodegradable Temporising Matrix is a 2mm

then admitted to hospital for acute infection and

bioabsorbable, biocompatible foam that consists of a

severity of ulcers, V.A.C VeraFlo therapy initiated

lower surface that allows for cellular infiltration and

with a cleanse choice dressing, taken to Operating

provides a scaffold for the dermis reconstruction,

Theatre for staged debridement and VeraFlo therapy,

with a sealing membrane over the top. This acts as a

SomaGen dermal matrix placed as tissue scaffold for

scaffold for granulation tissue to enter with a seal to

tissue replacement, Salera placental allograft placed

prevent tissue coalescing on the surface. It modifies

to optimize healing, Incisional V.A.C therapy initiated

the granulation and scar to form a dermal-like layer.

with PREVENA CUSTOMISABLE dressing immediately

Once the clinician has debrided the wound, it has a

following closure.

missing dermis that needs to be reconstructed. BTM can be draped over the wound like a garment,with

The summary of this situation concluded that an

pieces

placed

opposition

(edge-to-edge)

Wound Masterclass - Vol 2 - December 2023

Global Innovation in Wound Care Summit Series: What Do I Need to Know About Skin Substitutes?

“The polymer in BTM doesn't get digested and therefore it can integrate if the fluid collections are drained and the infection treated using standard of care.”

and secured in place using staples or sutures. Over

Wagstaff continues to explain that the indications

a period of 2-5 weeks, depending on the age and

for using this approach would be in deep wounds

physiological state of the patient, the tissue grows

that are unable to support a skin graft (exposed

into the foam and integrates, as confirmed by

bones that have been drilled or burred to a point

capillary refill. The top layer can then be delaminated

of bleeding, exposed tendons, or exposed vital

by gently peeling off the sealing membrane. Once this

structures), wounds susceptible to graft contracture

layer has been removed, there is a nice bed for skin-

(across the joints and/or neck area), where there is

grafting to occur.

indication of an improved outcome in comparison to a skin flap (too bulky or local flaps unavailable), and if

Prof. Wagstaff explains that even during the early

the patient is unfit for a longer procedure.

outcomes of BTM treatment, the coverage of the skin was soft and robust in appearance and texture. There is a better reconstructive approach when

Global expert

initiating treatment with BTM, in comparison to

Dr John Lantis

simply debriding the wound before undertaking skin-

Chief and Professor of Surgery, Mount Sinai West Hospital and Icahn School of Medicine

grafting methods. There are 3 major ops for burns to consider:

New York NY, United States

Day 0; Immediate excision

Day 2-3; Re-excise and apply BTM to wound.

and Dr J. Lantis around his experience with skin

Simpler than grafting, less invasive and shorter

substitutes. Lantis is a leading expert in this field of

operation

wound care and Dr Shamsian begins the questioning

We now go to the discussion between Dr N. Shamsian

by asking specifically about what the potential biggest 3.

3-5 week cooling off period; graft when the

change over the last decade in clinical practice is.

patient is physiologically well and integrated,

Lantis responds to state there has been exponential

all superficial wounds healed means there is

growth in the number of substitutes available for

more donor site, patient is systemically stronger,

experts and clinicians to utilize in the hospital setting,

nutritional support, joints mobilized and there is

and an amplification in the media regarding patients

more reliable and faster donor site healing

being more aware of the products available; what is deemed the most beneficial and appropriate within

Wagstaff mentions that this approach means that

practice. Lantis further explains that there is an

burn management has been less tiring and stressful,

emphasis on experimenting with novel products more

and that the results are more reliable with the quality

arduously, hence the development and proliferation

of scarring improved. Dr N. Shamsian questions

of fish-skin substitution. Acellular fish-skin is now

whether the BTM can become infected, to which the

being considered a close substitute that Dr Shamsian

informed response is that BTM prevents dressing

classifies as a biological substitute, demonstrating

activity or physical cleansing to the wound site,

a closeness to human skin. Lantis explains that

so colonization or collections can occur. Wagstaff

fish-skin has an extracellular matrix coming from a

notes that this tends to happen around the second

xenograft and is a non-human source. The primary

week of treatment, however, BTM is like a petri dish;

mode of obtaining this type of substitute is through

the underlying tissue is agar, and that is not what

Icelandic Cod, through medical analysis, which has

becomes infected. The polymer in BTM doesn't get

a consistency of cells embedded within a network

digested and therefore it can integrate if the fluid

of non-living tissue; a likeness to that of human

collections are drained and the infection treated

skin. Lantis explains the overview of the product as

using standard of care.

follows; Acellular fish-skin for medical use patented

Wound Masterclass - Vol 2 - December 2023

Global Innovation in Wound Care Summit Series: What Do I Need to Know About Skin Substitutes?

“Allografts can cause failure, if the skin graft is rejected by the host. Embryonic tissue has a dense barrier membrane with no cellular ingrowth, inhibiting the healing process and regeneration of tissue.”

by Kerecis. Fish-skin consists of cells embedded in

time and can either be a singular application or

a network of non-living cells (like human skin). CE

reapplied as a sequential depending on factors such

marked and FDA cleared. Manufactured with 100%

as physiological conditions of the patient. We can

renewable energy. Proteins and lipids are maintained

consider fish-skin to be a multiple-use product due

in their natural state. Decellularized and sterilized,

to this situation, where the single application can be

non-allergenic and biocompatible. Contains a biologic

carried out in the hospital setting, or at outpatients as

matrix, cells initially removed from the product itself.

a multiple-use product.

Lantis further explains that it is rare for people

Lantis further endeavors to state that there are four

to have an allergic or anaphylactic reaction to the

hallmarks of Kerecis Technology.

substitute as it is made from cod-skin (a fish), rather than produced from shellfish which is a common

allergy in the modern age.

Natural structure

3-D

Structure

with

–

chemical

Instant

natural

complexity

immutable by synthesis or even the most Excluding the scales and DNA associated with fish,

advanced

engineering,

natural

tissue

specifically cod, the skin itself is identical to human

degeneration, rightpore size, chemicals and

skin and the benefit is that viruses in cold water fish

signals, fatty acid profile and tensile tissue

do not have utility within human bodies, therefore there is no risk of contamination of disease associated

Natural Mechanical Properties – Strong and

with fish. The cells are removed using a gentle

preservers superior handling characteristics,

process, otherwise classified as ‘Patented Processing’.

handles like skin, pliable and easy to suture and

This removes the risk for a harsh viral inactivation

staple, surgeons favor this for ease and efficacy

process by a lack of transmission risk, and therefore

Natural Molecular Content – Lipid rich biological

no strong alcohols, detergents, mechanical pressing,

barrier that protects against pathogens, limits

or tampering is needed. These factors have a major

irritation, and modulates tissue response with a

benefit on the cost-effectiveness at market value

chemical complexity of the fish skin promoting

with no crosslinking. All of the skin components are

rapid skin regrowth and neovascularization

Omega3 rich and provide proteins, glycans and fats that humans require to regenerate healthy layers of

Natural Molecular Organization – Unique gentle

skin; encouraging the healing process. Lantis explains

processing, thousands of proteins, lipids and

that the graft is applied to human wounds where it

glycans are natively organized and mimic natural

recruits stem cells and regular cells to facilitate the

tissue ingrowth

tissue regeneration. Fish-skin is a robust substitute and can be combined When we compare fish-skin substitution to human

with mesh when applying to the surface of the wound.

allografts and embryonic tissue, there are differences.

Lantis explains that in this instance, it is better to affix

Allografts can cause failure, if the skin graft is rejected

the material with either staples or sutures for security

by the host. Embryonic tissue has a dense barrier

and a tactile approach that is less invasive or painful,

membrane with no cellular ingrowth, inhibiting the

essentially improving patient outcomes. Cod is a very

healing process and regeneration of tissue.

large fish so the sheets of fish-skin are essential for larger wounds. The molecular content breakdown

A key phrase of viewing the fish-skin like a dermal

is as follows; Collagen, Elastin, Laminin, Fibronectin,

scaffold

when

Proteoglycan, Glycols amino-glycans, Lipids (with

deliberating the effectiveness of technique and

Omega3). Alongside this beneficial structure, the

application. Lantis explains that the product itself

pore size of fish-skin is similar to human skin as well

modulates the wound bed, which can be seen over

as being very thick. Lantis goes on to explain ‘How

essential

consideration

Wound Masterclass - Vol 2 - December 2023

Global Innovation in Wound Care Summit Series: What Do I Need to Know About Skin Substitutes?

“Some of the indicators for using fish skin would be diabetic foot wounds, venous leg ulcers, post-surgical wounds, burns, and skin-graft donor sites.”

To Use’ or ‘Best Practice’ when applying this as a

of Kerecis begin to adhere to the wound bed, they

substitute in 8 steps;

should be removed with a reapplication of new sheets if those have been partially absorbed or are no longer

Remove necrotic tissue

visible. It is essential to change the wound dressing to maintain the moist environment.

Remove exudate and control bleeding

Remove the fish skin sheet from the pouch in an

temperature in a sterile packaging which will ensure

aseptic manner

a minimum of 2-year shelf life. It is important to note

The fish-skin itself should be stored at room

that they will be delivered in boxes of 10, which is 4.

Cut the sheet roughly to the size of the area to be

essential when managing patients that require a

covered

multiple-use purpose. Some of the indicators for using fish skin would be diabetic foot wounds, venous

Pre-hydrate with NaCl solution

leg ulcers, post-surgical wounds, burns, and skin-graft donor sites.

Apply sheet to wound, ensure no overlap of wound edges

double-blind,

randomized

clinical

trial

was

conducted on 162 wounds (81 patients) where one 7.

More than one sheet may be necessary for

wound was treated with Porcine and the other with

complete coverage. Overlap sheet edges to

Fish-skin as a substitute. The fish-skin demonstrated

ensure coverage

a significantly faster healing rate, and the same model was reproduced 5 years later with Fish-skin against

Apply appropriate non-adherent wound dressing

Amnion/Chorion Products, which, again proved a

to maintain moist environment

significantly faster healing rate.

Dr N. Shamsian goes on to question ‘Are you doing

A study specifically for diabetic foot wounds where

something similar with this technique, and with a skin

Fish-skin was utilized vs. SOC (Standard of Care), once

cavity, are you overlapping the sides of the so the

again proved a faster healing rate. It is important to

defects are covered?’, to which Lantis responds with

consider that this study was conducted on significantly

a ‘Yes’. Allowing the wrap up to go around the size,

‘sicker’ patients with a preemptive comorbidity, in

even when you don’t have the right size substitute,

comparison to the previous 2 studies that were

with someone experienced in this area of treatment

conducted on younger and healthy individuals. The

you can morcellate or cut-up the product not to cover

wounds were harder to heal in the initial stages due

the entire wound, even though the preference is to

to this physiological condition, but again the efficacy

cover the entire area. Bu using deep quilting stiches,

was proven, and patients complained more about

we cauterize the defects that occur, and it is essential

pain and infection risk when utilizing the approach of

to keep this area moist as, if the area becomes dry,

SOC, in comparison to that of the fish-skin. Therefore,

the material may not stick to the wound, as described

we can deduce that fish-skin is more cost effective

by Lantis with the following anecdote: A fish does not

and improves overall patient outcomes.

like to be out of water. There are wounds that fish skin would not be Follow-Up

appropriate to use as a form of management and/or treatment, and this includes (but is not

Inspect the wound every 2-3 days depending on the

limited too); Acutely infected wounds (cellulitis),

amount of exudate, followed by cleaning the wound

over untreated osteomyelitis (bone infections not

areas as needed. If the previously applied sheets

previously treated), or directly over anastomosis.

Wound Masterclass - Vol 2 - December 2023

Global Innovation in Wound Care Summit Series: What Do I Need to Know About Skin Substitutes? Lantis gives the audience some helpful tips and tricks

every patient is the same. Product ‘X’ may be used

when considering the utilization of fish skin substitution:

for a period, then we move to a combined approach

Cut to size once the substitute is dry. Fenestrate

with fish- skin substitution, then we may add human

when wet.Suture whenever possible (Chromic suture

skin. There is no scope for layering the methodology

are best applicable). You can sew to the base of the

as of the moment, Lantis explains, but having this

wound. Keep the area hydrated (cover with Hydrogel).

combined approach to treatment may improve the

Finally, Dr N. Shamsian concludes by questioning ‘In

healing response. Even though there are new biologic

terms of the future for skin substitutions, what will the

and non-biologic products being adapted and tested

next stage be?’ and Lantis explains that essentially,

all the time, the future is uncertain without the

we need better algorithms as clinicians. We need

essential need for an algorithm that is informed and

to look at wounds with the understanding that not

based on specifics like disease or wound type.

Supported by

Wound Masterclass - Vol 2 - December 2023