From Grafts to Human Bioengineered Vascularized Skin Substitutes
Abstract
:1. Introduction
2. Chronological Review
3. Clinical Demands for Bioengineered Artificial Skin Substitutes (BASS)
3.1. Ethical and Legal Requirements
3.2. Protective Functions and Resistance to Infection
3.3. Biological Functions
3.4. Able to Prevent Water Loss and Water Accumulation
3.5. Adhesiveness
3.6. Low Antigenicity
3.7. Conform to Irregular Wound Surfaces
3.8. Withstand Shear Forces and Mechanical Tensions
3.9. Hypoxia Tolerant
3.10. Dermal and Epidermal Components
3.11. Easy to Prepare
3.12. Long Shelf Life and Easily Storage
3.13. Suitable Cost/Effectiveness
4. Skin Substitutes Classification
- I.
- Cultured epidermal substitutes
- II.
- Dermal components coming from skin or extracellular matrix (ECM) components
- III.
- Substitutes that include both dermal and epidermal components.
Temporary Skin Substitutes
5. Commercially Available Skin Substitutes
6. Trilayered Skin Substitutes
6.1. Importance of Vascularization in Wound Healing
6.2. Strategies for Vascularization
6.2.1. Angiogenic Strategies
6.2.2. Prevascularization Strategies
7. Future Perspectives
Funding
Conflicts of Interest
Abbreviations
Ad-MVF | Adipose-tissue Derived Microvascular Fragments |
AECs | Amniotic Epithelial Cells |
AMCs | Amniotic Mesenchymal Cells |
ASC | Adipose Stromal Cells |
ATRA | All-trans Retinoic Acid |
ATMPs | Advanced Therapy Medicinal Products |
AV-loop | Arteriovenous Loop |
BASS | Bioengineered Artificial Skin Substitutes |
BM-MSC | Bone Marrow Mesenchymal Stem Cells |
CEA | Cultured Epidermal Autograft |
DCs | Dendritic Cells |
DFUs | Diabetic Foot Ulcers |
dsASCs | Discarded Skin Adipose Stromal Cells |
GCP | Good Clinical Practice |
GMP | Good Manufacturing Practice |
EC | Endothelial Cells |
ECM | Extracellular Matrix |
EMA | European Medicines Agency |
EPCs | Endothelial Progenitor Cells |
FDA | Food and Drug Administration |
FDCA | Food, Drug and Cosmetic Act |
FGF | Fibroblasts Growth Factor |
HAM | Human Amniotic Membrane |
HBOEC | Human Blood Outgrowth Endothelial Cells |
HDMEC | Human Dermal Microvascular Endothelial Cells |
HUVEC | Human Umbilical Vein Endothelial Cells |
IL | Interleukin |
IRB | International Review Board |
MHC | Major Histocompatibility Complex |
NK | Natural Killer |
PEG | Polyethyleneglycol |
PHSA | Public Health Services Act |
STSG | Split-Thickness Skin Grafts |
SVF | Stromal Vascular Fraction |
TBSA | Total Body Surface Area |
TGF | Transformant Growth Factor |
VEGF | Vascular Endothelial Growth Factor |
VLUs | Venous Leg Ulcers |
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Type of Temporary Cover | Example | Description |
---|---|---|
Xenogeneic decellularized skin | E-Z Derm® Mölnlycke | Porcine xenograft for skin loss injuries |
Allogenic cadaveric human skin | Euro Skin Bank | Donated human skin allografts derived from cadavers |
Human amnion | EpiBurn® Mimedx | Dehydrated human amnion allograft which acts as a protective barrier and promotes healing |
Synthetic dressings | Gauzes or hydrocolloids | Covers made of synthetic materials |
Alternative natural skin covers | Banana leaves Potato peel | Natural covers used specially on developing countries |
Commercial Brand | Cell Content | Source | Conformation | Anatomical Structure | Type of Biomaterial | Description | Clinical Use |
---|---|---|---|---|---|---|---|
AlloDerm® [67] | Acellular | Allogeneic | Bi-layered | Dermal | Biological | Donated allograft human dermis decellularized and freeze-dried with a “dermal” side and a “basement membrane” side | Gingival augmentation, dental roots cover, burns |
Apligraf® [45] | Cellular | Allogeneic | Bi-layered | Composite | Biological | Human foreskin neonatal keratinocytes and fibroblasts within a bovine type I collagen matrix | Licensed only for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) |
Biobrane® [58,68] | Acellular | Xenogeneic | Bi-layered | Dermal | Biosynthetic | Semipermeable silicone film partially imbedded in a 3D network of nylon functionalized with porcine collagen type I | Superficial partial thickness burns |
Bioseed-S [69] | Cellular | Autologous | Single-layer | Epidermal | Biological | Autologous keratinocytes suspended on a fibrin sealant | Therapy-resistant chronic VLUs |
CryoSkin [47] | Cellular | Allogeneic | Spray | Epidermal | Biological | A cell spray made of keratinocytes isolated from newborn foreskin cultured on silicone | Superficial wounds. |
Dermagraft® [48] | Cellular | Allogeneic | Single-layer | Dermal | Biological | Foreskin fibroblast which secrete growth factors and ECM seeded on a bioabsorbable polyglactin mesh scaffold | Stalled diabetic foot ulcers (DFUs), other clinical indications |
EPIBASE® [51,70] | Cellular | Autologous | Single-layered | Epidermal | Biological | Keratinocytes isolated from a small biopsy expanded originating CEA that is sprayed on the wound | Cutaneous calciphylaxis, burns |
Epicel® [71] | Cellular | Autologous | Single-layered | Epidermal | Biological | Keratinocytes attached to a petrolatum gauze support | Deep dermal burns |
EpidexTM® [50] | Cellular | Autologous | Single-layered | Epidermal | Biological | Expanded epidermal keratinocytes precursor cells derived from the follicular outer root sheath (ORS) by plucking hair armed on a sillicone membrane disc | Chronic leg ulcers |
GraftJacket® [72] | Acellular | Allogeneic | Single-layered | Dermal | Biosynthetic | Human dermal collagen matrix with vascular channels | Rotator-cuff-tears |
Hyalograft 3D® [73] | Cellular | Autologous | Single-layered | Dermal | Biological | Autologous fibroblasts seeded on a hyaluronic acid scaffold | Full-thickness and deep partial wound |
Integra® [59] | Acellular | Xenogeneic | Bi-layered | Dermal | Biosynthetic | Matrix of bovine derived collagen fibers, chondroitin-6-sulphate and a silicone sheet that acts as a barrier | Burns or reconstructive surgery |
Laserskin® [73] | Cellular | Autologous | Single-layered | Epidermal | Biosynthetic | Cultured keratinocytes on a hyaluronic acid microperforated membrane | Wound resurfacing |
Matriderm® [60] | Acellular | Xenogeneic | Single-layered | Dermal | Biosynthetic | A decellularized dermal substitute of bovine origin with collagen matrix coated with -elastin hydrolysate | For split thickness skin grafting (STSG) |
OASIS® [74] | Acellular | Xenogeneic | Single-layered | Composite | Biological | Matrix derived from porcine small intestinal submucosa | Wound closure, full-thickness ulcers |
OrCel® [54] | Cellular | Allogeneic | Bi-layered | Composite | Biological | Epidermal keratinocytes and dermal fibroblasts co-cultured in separate layers, into a type I bovine collagen sponge matrix | Severely burned patients |
Permacol™ surgical implant [63] | Acellular | Xenogeneic | Single-layered | Dermal | Biological | Decellularized dermal porcine containing collagen and elastin | Specially used for abdominal wall hernia and dermal reconstruction |
PolyActive® [75] | Cellular | Autologous | Bi-layered | Composite | Biological | Soft polyethylene oxide terephthalate component and a hard polybutylene terephthalate component with a keratinocytes and fibroblasts | Not specified |
Recell® [76] | Cellular | Autologous | Single-layered | Epidermal | Biological | Keratinocytes and melanocytes spray | Depth burns |
Suprathel® [64] | Acellular | Cell-free | Single-layered | Epidermal | Synthetic | Porous membrane made of a co-polymer (terpolymer) of poly-dl-lactide, trimethylene carbonate and ε-caprolactone | Partial thickness burns and abrasions |
SureDerm® [77] | Acellular | Allogeneic | Bi-layered | Composite | Biosynthetic | Decellularized human dermis coated with gelatin | Exposed orbit after exenteration |
Terudermis® [66] | Acellular | Xenogeneic | Bi-layered | Dermal | Biological | Bovine lyophilized cross-linked collagen sponge made of collagen with silicone sheet. | Burns with muscle or bone exposition |
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Oualla-Bachiri, W.; Fernández-González, A.; Quiñones-Vico, M.I.; Arias-Santiago, S. From Grafts to Human Bioengineered Vascularized Skin Substitutes. Int. J. Mol. Sci. 2020, 21, 8197. https://doi.org/10.3390/ijms21218197
Oualla-Bachiri W, Fernández-González A, Quiñones-Vico MI, Arias-Santiago S. From Grafts to Human Bioengineered Vascularized Skin Substitutes. International Journal of Molecular Sciences. 2020; 21(21):8197. https://doi.org/10.3390/ijms21218197
Chicago/Turabian StyleOualla-Bachiri, Wasima, Ana Fernández-González, María I. Quiñones-Vico, and Salvador Arias-Santiago. 2020. "From Grafts to Human Bioengineered Vascularized Skin Substitutes" International Journal of Molecular Sciences 21, no. 21: 8197. https://doi.org/10.3390/ijms21218197