WOUND CARE UPDATE. -Commonly Used Skin Substitute Products For Wound. -Total Contact Casting. Jack W. Hutter DPM, FACFAS, C. ped.

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1 WOUND CARE UPDATE -Commonly Used Skin Substitute Products For Wound Closure -Total Contact Casting Jack W. Hutter DPM, FACFAS, C. ped.

2 Commonly Used Skin Substitute Products for Wound Closure why are they necessary? Chronic wounds are stuck in the inflammatory healing phase First, the basics

3 Wound healing phases Inflammatory phase Proliferative phase Remodeling phase

4 Wound healing phases Inflammatory phase During the first two days - neutrophils arrive to clean up the wound from necrotic debris - macrophages provide further cleansing, and growth factor production - platelets also produce growth factors

5 Wound healing phases Proliferative phase Duration from day 3 to two weeks --fibroblast migration to produce extracellular matrix ( ECM ) -- inhibition of metalloproteinase's -- growth factors stimulate epithelization, angiogenesis

6 Wound healing phases Remodeling phase From 2 weeks to 1 year - increased tensile strength - wound contraction - reduction in number of macrophages, fibroblasts, and in metabolic activity

7 Why do wounds stall in the inflammatory phase? Disease states such as diabetes mellitus Inadequate offloading Vascular insufficiency Vasculitis These conditions lead to a disruption in the healing process, thus the wound cannot get to the proliferative phase

8 How does this stalling process occur? Infection Low po2 Necrosis High levels of inflammatory cytokines Increased metalloproteinase activity The above elicit an excessive neutrophil response, causing chronic inflammation, which leads to ECM breakdown, and growth factor destruction

9 Diabetic foot ulcers. Greater than 30 days duration, 5 fold increase in risk of infection Infection and wound duration are primary contributing factors to inflammatory phase stall 24% healing rate after 12 weeks of standard wound care ( debridement, topical antimicrobials and wound healing medications, off loading )

10 Chronic wounds are those that do not show at least 50% reduction in four weeks of standard wound care Advanced therapies are indicated in these cases What can be done to mitigate this?

11 The magic bullets Human dermal matrix substitutes Bovine dermal matrix substitutes Non-placenta derived human mesenchymal stem cells Placenta derived human mesenchymal stem cells

12 Utilization of undifferentiated mesenchyme stem cells shows significant improvement in wound repair MSC Bone marrow and placenta are common sites for stem cell/stem cell constituent harvest MSC have been shown to positively influence all three phases of wound repair

13 Human mesenchyme stem cells ( MSC )stimulate the non-healing wound to leave the inflammatory phase to enter the proliferative phase MSC anti-inflammatory properties which help to restart chronic wounds MSC antimicrobial activity reduces infection in the inflammatory phase

14 MSC wound repair benefits during the proliferative phase Facilitation of regeneration, granulation, epithelization, with recent studies showing an 85 90% reduction in wound size within 4 weeks Cellular responses controlled by MSC include cell survival, cell proliferation, migration, gene expression, anti-scarring, growth factor balance

15 During the remodeling phase, regulation of reorganization of the healed wound MSC conditioned medium stimulates keratinocytes, dermal fibroblasts, endothelial cells in the remodeling, strengthening of the previous wound site Recent studies show that the addition of MSC allows for only a 6 % reoccurrence rate over 1 year

16 What tissues are utilized to harvest mesenchymal stem cells? Bone marrow Adipose tissue Umbilical cord Amniotic membrane Human foreskin

17 The placenta MSC has similar, possibly greater, benefits than the general MSC The human amniotic membrane contains structural collagens, extracellular matrix, many cell line growth factors, multiple healing cytokines Antimicrobial, immunosuppressive, scar reducing properties Potentially a more powerful tool than a general MSC line

18 Amniotic membrane tissue for wound treatment was first attempted over 100 years ago During the last 50 years amnion/chorion allografts have been used in many applications Chronic neurotrophic wounds, corneal surface wounds, dental applications, orthopedic and general surgery, neurosurgery The advent of new processing techniques has generated additional interest in utilizing these grafts in wound care

19 Previously there were concerns regarding the use of human amniotic membrane relative to obtaining, preparing, storing the tissue Concerns about infectious disease transmission, rejection, shelf life New cryogenic and dehydration techniques have helped to address these issues

20 The human amniotic membrane - Amnion and chorion layers both specifically contain substantial numbers of growth factors and healing cytokines - Grafts containing amniotic membrane alone tend to be thinner, less durable, faster to resorb

21 Methods of MSC application Systemic administration, with or without topical application Intramuscular injections Topical suspensions in fibrin glue, collagen sponge, Bioabsorbable scaffold, cryogenic preparation Topical powder, dehydrated preparation Most topical applications are contraindicated if exposed tendon, bone (Apligraf, Grafix exceptions) Topical applications also contraindicated if infection

22 Commonly used wound healing skin substitute products Human dermal matrix dermagraft, apligraf, Paraderm Bovine dermal matrix - Primatrix Human placenta membrane tissue Grafix Epifix, -There are many others, practitioner preference

23 Skin substitutes obtained from human dermal matrix Dermagraft Treatment of full thickness DFU Human fibroblast cells from a qualified cell bank seeded to a bioabsorbable scaffold Creates a dermal substitute containing collagen, extracellular matrix proteins, growth factors, cytokines Cryogenically preserved Multiple weekly applications, 6 month shelf life Studies indicate wound closure 40% of cases over 12 weeks compared to control of 23% 90,000 patients over 11 years Contraindicated if infection or exposed bone or tendon

24 Skin substitutes obtained from human dermal matrix Apligraf Full thickness DFU and venous ulceration Bilayered, containing living human keratinocytes and fibroblasts obtained from neonatal foreskin Cultured and expanded, decontaminated, cryopreserved Contains collagen, ECM proteins, growth factors, cytokines Studies indicate mean wound closure 56-70% within 12 weeks Multiple applications 100,000 cases over at least 11 years

25 Skin substitutes obtained from human dermal matrix Paraderm Full thickness DFU Epidermis and epidermal appendages ( glands, hair follicles ) and dermal cellular elements removed Dermal matrix remaining, with elastic fibers, collagen strands, basement membrane and blood vessel channels intact Allows for rapid revascularization due to intact blood vessel channels Does not contain appreciable amounts of growth factors

26 Skin substitutes obtained from bovine dermal matrix Primatrix Full or partial thickness wounds Dermal matrix scaffold Bovine fetal tissue, rich in type III non-denatured collagen Does not contain appreciable amounts of growth factors Highly porous, ensuring rapid matrix revascularization Shelf life 3 years, room temperature Multiple sizes allow for cost effectiveness

27 Skin substitutes obtained from human placenta membrane tissue Epifix Human placenta amnion/chorion membrane allograft Positively affects cell proliferation, inflammation reduction, metalloproteinase reduction with substantial variety of growth factors and healing cytokines Prepared by separation of placenta tissue, cleansing, sterilization, reassembly, dehydration Sheet configuration, injectable solution, micronized powder, cost effective Since 2007, 120,000 applications including full or partial thickness DFU, eye surgery, burns, orthopedics, plastics, neurosurgery, OBGYN 5 year shelf life Mean wound closure time 3 weeks, 94% closure rate

28 Human placenta membrane processing Dehydration compared to cryopreservation Dehydration yields an increased number of active growth factors Shelf life similar Storage easier with dehydrated graft material More methods of application with dehydrated material Viable membrane cells post thaw, compared to cell contents derived from dehydration process

29 Skin substitutes obtained from human placenta membrane tissue Grafix Acute or chronic partial or full thickness DFU Cryopreserved Available as amniotic membrane alone or amnion/chorion combined Combination membrane used intially for extremely chronic (stalled ) wounds Can be used over non-infected exposed bone, tendon Similar amounts, types of growth factors as Epifix?

30 Grafix application

31 Grafix application

32 Total contact casting The best and most cost effective weapon we have for DFU closure Provides a higher percentage of healing when compared to other methods of offloading 90% TCC, 65% removable cast walker, 58% half shoe - Armstrong et al. Diabetes Care, 2001 The highest reduction of forces at impact, least velocity of shear, least repetitive stress Seals out contaminants, bacteria Healing time depends upon severity Reapply every 7-10 days wound measurement, photograph Adding skin substitutes can accelerate healing Contraindicated if infection, DVT history Weight bearing clinician preference

33 Total contact casting Traditional TCC Instant TCC Acute or chronic partial or full thickness DFU without infection Stage 1 acute Charcot osteoarthropathy Stage 3 chronic osteoarthropathy with ulceration, without infection Prefabricated cast modified to function as a TCC As effective as traditional TCC in pressure reduction, not equivalent regarding healing time, If frequent reapplication is needed, select removeable cast walker alone, as instant TCC is not as easily reapplied Instant TCC used if traditional system is not available or if closer monitoring of the foot is needed - Armstrong et al. JAPMA 2002

34 Total contact casting Multiple pre-made systems are available

35 Total contact casting Wound debridement Wound dressing

36 Total contact casting Cutimed Off-Loader Select Total Contact Casting System

37 The desired result. The two year road for this patient has ended happily, for now

38 Thank You