Published : 29 September 2025

Current Updates of Biomaterials for Skin Replacement: A Systematic Review

  • Normalina Sandora
  • Nur Amalina Fitria
  • Aditya Wardhana
  • Nandita Melati Putri
  • Akhmad Noviandi Syarif
  • Tyas Rahmah Kusuma
  • Benati Karimah

Volume 12, Issue 2, Jurnal Plastik Rekonstruksi | Pages : 97-108

DOI: 10.14228/jprjournal.v12i2.45   Reader : 4 times PDF Download : 6 times

Abstract

Background: The human skin envelops the entire body surface and is highly susceptible to damage. Partial- and full-thickness skin loss often necessitates the use of skin substitutes. Autologous grafting remains the gold standard for skin replacement. Furthermore, the application is usually constrained by the limited availability of donor skin, the technical challenges of surgery, and the added difficulties encountered in severe cases. In this systematic review, we summarise the strengths and limitations of biological and synthetic biomaterials as skin substitutes, with evidence drawn from clinical practice, human trials, and preclinical animal studies. This systematic review evaluates the advantages and disadvantages of biological and synthetic biomaterials used as skin substitutes, drawing evidence from clinical practice, human studies, and animal studies.”
Method: We performed a comprehensive literature review using the search engines OVID, ScienceDirect, Google Scholar, and PubMed databases. Search terms or keywords included "artificial skin," "biomaterials," "skin substitute," "full-thickness burn," "synthetic materials," "burn graft materials," and "wound care." From an initial pool of 97 articles, 65 met the inclusion criteria, which required peer-reviewed studies published in English after 2000, focusing on biomaterials for skin substitutes evaluated in clinical, human, or animal studies.
Results:  Skin substitutes commercially available in the market were predominantly incorporated with human fibroblasts and keratinocytes within a three-dimensional matrix, with a preference for biological materials due to their biocompatibility. Nevertheless, biological substitutes face challenges such as limited availability, extended production time, high costs, and lack of immediate usability. In contrast, synthetic substitutes are more accessible and scalable but often do not integrate well with the recipient's tissue, which limits their clinical efficacy.
Conclusion: While both biological and synthetic artificial skin substitutes are available on the market, none of the current options fully meet the ideal criteria for skin replacement, such as affordability, availability, seamless integration with the surrounding tissue, and the ability to minimise scarring. More research is needed to address these limitations and advance the development of next-generation biomaterials that can effectively replace skin.

Data Availability

All data generated during this study are included in this published article [and its supplementary information files].

References

  1. 1. Shevchenko RV, James SL, James SE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. Journal of the royal Society Interface. 2010;7(43):229-58.
  2. 2. Saad HA, Elsayed AA, Eraky ME, Elsayed RS, Riad M. On Postoperative Problems Following Mastectomy and Their Impact on Immediate Breast Reconstruction, Early Neoadjuvant and Adjuvant Chemotherapy. The Egyptian Journal of Hospital Medicine. 2023;91(1):4327-32.
  3. 3. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Critical care. 2015;19:1-12.
  4. 4. Tavakoli S, Klar AS. Bioengineered skin substitutes: Advances and future trends. Applied Sciences. 2021;11(4):1493.
  5. 5. Deng P, Shi H, Pan X, Liang H, Wang S, Wu J, et al. Worldwide research trends on diabetic foot ulcers (2004–2020): suggestions for researchers. Journal of Diabetes Research. 2022;2022(1):7991031.
  6. 6. Hartmann J, Schüler S, Enk A, Lonsdorf A. Skin cancer in organ transplant recipients: dynamics in the incidence and clinical predictors for the first and subsequent post‐transplant non‐melanoma skin cancer. Journal of the European Academy of Dermatology and Venereology. 2019;33(7):1281-9.
  7. 7. Sasor SE, Chung KC. Upper extremity burns in the developing world: a neglected epidemic. Hand clinics. 2019;35(4):457-66.
  8. 8. Peck M, Molnar J, Swart D. A global plan for burn prevention and care. Bulletin of the World Health Organization. 2009;87:802-3.
  9. 9. Saavedra PAE, Leal JVDO, Areda CA, Galato D. The costs of burn victim hospital care around the world: a systematic review. Iranian journal of public health. 2021;50(5):866.
  10. 10. Hop MJ, Polinder S, van der Vlies CH, Middelkoop E, van Baar ME. Costs of burn care: a systematic review. Wound repair and regeneration. 2014;22(4):436-50.
  11. 11. Kemenkes. Anggaran Kesehatan Kementrian Kesehatan RI 2024. kemenkesgoid2024.
  12. 12. Yannas I, Burke JF. Design of an artificial skin. I. Basic design principles. Journal of biomedical materials research. 1980;14(1):65-81.
  13. 13. Bhattacharjee NV, Schumacher AE, Aali A, Abate YH, Abbasgholizadeh R, Abbasian M, et al. Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. The Lancet. 2024;403(10440):2057-99.
  14. 14. O'Connor N, Mulliken J, Banks-Schlegel S, Kehinde O, Green H. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. The Lancet. 1981;317(8211):75-8.
  15. 15. Green H. The birth of therapy with cultured cells. Bioessays. 2008;30(9):897-903.
  16. 16. Elfawy LA, Ng CY, Amirrah IN, Mazlan Z, Wen APY, Fadilah NIM, et al. Sustainable approach of functional biomaterials–tissue engineering for skin burn treatment: a comprehensive review. Pharmaceuticals. 2023;16(5):701.
  17. 17. Schmitz M, Eberlein T, Andriessen A. Wound treatment costs comparing a bio-cellulose dressing with moist wound healing dressings and conventional dressings. Wound Medicine. 2014;6:11-4.
  18. 18. Djaprie SM, Wardhana A. Dressing for Partial Thickness Burn Using Microbial Cellulose and Transparent Film Dressing: A Comparative Study. Jurnal Plastik Rekonstruksi. 2013;2(2).
  19. 19. Kim JJ, Franczyk M, Gottlieb LJ, Song DH. Cost-effective alternative for negative-pressure wound therapy. Plastic and Reconstructive Surgery–Global Open. 2017;5(2):e1211.
  20. 20. Shimizu R, Kishi K. Skin graft. Plast Surg Int 2012. 2012.
  21. 21. Serebrakian AT, Pickrell BB, Varon DE, Mohamadi A, Grinstaff MW, Rodriguez EK, et al. Meta-analysis and systematic review of skin graft donor-site dressings with future guidelines. Plastic and Reconstructive Surgery–Global Open. 2018;6(9):e1928.
  22. 22. Putri NM HC, Wardhana A, Sandora N. Peran Ko-kultur Keratinosit dan Sel Punca Epitel Amnion pada Graft Amnion Bilayer pada Penyembuhan Luka Bakar: Kajian terhadap TGF-β1, TGF-β3, Wnt4, MMP-2, MMP-9, Epitelisasi Luka, Ketebalan Epidermis, dan Skor Histologis = The Role of Human Amniotic Epithelial Cells and Keratinocytes Co-culture on Acellular Amnion Bilayer Graft in TGF-β1, TGF- β3, Wnt 4, MMP-2, MMP-9 Gene Expression, Epithelization, Epidermal Thickness and Histological Score in Burn Patients Wound Healing. disertasi. 2024.
  23. 23. Mogoşanu G, Popescu FC, Busuioc CJ, Pârvănescu H, Lascăr I. Natural products locally modulators of the cellular response: therapeutic perspectives in skin burns. Romanian journal of morphology and embryology= Revue roumaine de morphologie et embryologie. 2012;53(2):249-62.
  24. 24. Zilberman M, Elsner JJ. Antibiotic-eluting medical devices for various applications. Journal of Controlled Release. 2008;130(3):202-15.
  25. 25. Gravante G, Di Fede M, Araco A, Grimaldi M, De Angelis B, Arpino A, et al. A randomized trial comparing ReCell® system of epidermal cells delivery versus classic skin grafts for the treatment of deep partial thickness burns. Burns. 2007;33(8):966-72.
  26. 26. Holmes IV JH. A brief history of RECELL® and its current indications. Journal of Burn Care & Research. 2023;44(Supplement_1):S48-S9.
  27. 27. Mohebichamkhorami F, Alizadeh A. Skin substitutes; an updated review of products from year 1980 to 2017. Journal of Applied Biotechnology Reports. 2017;4(3):615-23.
  28. 28. Maarof M, Law JX, Chowdhury SR, Khairoji KA, Saim AB, Idrus RBH. Secretion of wound healing mediators by single and bi-layer skin substitutes. Cytotechnology. 2016;68:1873-84.
  29. 29. Bianchi C, Cazzell S, Vayser D, Reyzelman AM, Dosluoglu H, Tovmassian G, et al. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix®) allograft for the treatment of venous leg ulcers. International wound journal. 2018;15(1):114-22.
  30. 30. Zelen CM, Serena TE, Gould L, Le L, Carter MJ, Keller J, et al. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi‐centre comparative study examining clinical efficacy and cost. International wound journal. 2016;13(2):272-82.
  31. 31. Hart CE, Loewen-Rodriguez A, Lessem J. Dermagraft: use in the treatment of chronic wounds. Advances in wound care. 2012;1(3):138-41.
  32. 32. Omar A, Mavor A, Jones A, Homer-Vanniasinkam S. Treatment of venous leg ulcers with Dermagraft®. European journal of vascular and endovascular surgery. 2004;27(6):666-72.
  33. 33. Curran MP, Plosker GL. Bilayered bioengineered skin substitute (Apligraf®) A review of its use in the treatment of venous leg ulcers and diabetic foot ulcers. BioDrugs. 2002;16:439-55.
  34. 34. Zaulyanov L, Kirsner RS. A review of a bi-layered living cell treatment (Apligraf®) in the treatment of venous leg ulcers and diabetic foot ulcers. Clinical interventions in aging. 2007;2(1):93-8.
  35. 35. Eaglstein WH, Alvarez OM, Auletta M, Leffel D, Rogers GS, Zitelli JA, et al. Acute excisional wounds treated with a tissue‐engineered skin (Apligraf). Dermatologic surgery. 1999;25(3):195-201.
  36. 36. Still J, Glat P, Silverstein P, Griswold J, Mozingo D. The use of a collagen sponge/living cell composite material to treat donor sites in burn patients. Burns. 2003;29(8):837-41.
  37. 37. Lavery LA, Fulmer J, Shebetka KA, Regulski M, Vayser D, Fried D, et al. The efficacy and safety of Grafix® for the treatment of chronic diabetic foot ulcers: results of a multi‐centre, controlled, randomised, blinded, clinical trial. International wound journal. 2014;11(5):554-60.
  38. 38. Wong T, McGrath J, Navsaria H. The role of fibroblasts in tissue engineering and regeneration. British Journal of Dermatology. 2007;156(6):1149-55.
  39. 39. Gibbons GW. Grafix®, a cryopreserved placental membrane, for the treatment of chronic/stalled wounds. Advances in wound care. 2015;4(9):534-44.
  40. 40. Landsman AS, Cook J, Cook E, Landsman AR, Garrett P, Yoon J, et al. A retrospective clinical study of 188 consecutive patients to examine the effectiveness of a biologically active cryopreserved human skin allograft (TheraSkin®) on the treatment of diabetic foot ulcers and venous leg ulcers. Foot & Ankle Specialist. 2011;4(1):29-41.
  41. 41. Ruszczak Z. Effect of collagen matrices on dermal wound healing. Advanced drug delivery reviews. 2003;55(12):1595-611.
  42. 42. Shores JT, Gabriel A, Gupta S. Skin substitutes and alternatives: a review. Advances in skin & wound care. 2007;20(9):493-508.
  43. 43. Geevarghese R, Sajjadi SS, Hudecki A, Sajjadi S, Jalal NR, Madrakian T, et al. Biodegradable and non-biodegradable biomaterials and their effect on cell differentiation. International Journal of Molecular Sciences. 2022;23(24):16185.
  44. 44. MacEwan MR, MacEwan S, Kovacs TR, Batts J. What makes the optimal wound healing material? A review of current science and introduction of a synthetic nanofabricated wound care scaffold. Cureus. 2017;9(10).
  45. 45. Rodriguez JC, Chen AH, Carney DE. Treatment of superficial second-degree burns with a nanofiber tissue matrix: A case report. Burns Open. 2022;6(4):173-6.
  46. 46. Husain K, Malik A, Kirchens J, Choi G. A prospective, blinded, randomized controlled clinical trial evaluating the effect of the synthetic electrospun fiber matrix in the treatment of chronic diabetic foot ulcers. Foot & Ankle Surgery: Techniques, Reports & Cases. 2024;4(1):100362.
  47. 47. Klar AS, Güven S, Biedermann T, Luginbühl J, Böttcher-Haberzeth S, Meuli-Simmen C, et al. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells. Biomaterials. 2014;35(19):5065-78.
  48. 48. Micka-Michalak K, Biedermann T, Reichmann E, Meuli M, Klar AS. Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo. Pediatric surgery international. 2019;35:129-36.
  49. 49. Meuli M, Hartmann-Fritsch F, Hüging M, Marino D, Saglini M, Hynes S, et al. A cultured autologous dermo-epidermal skin substitute for full-thickness skin defects: a phase I, open, prospective clinical trial in children. Plastic and reconstructive surgery. 2019;144(1):188-98.
  50. 50. Herron K. Impact of a novel synthetic nanofibre matrix to treat hard-to-heal wounds. Journal of Wound Care. 2022;31(11):962-8.
  51. 51. Kuang B, Pena G, Cowled P, Fitridge R, Greenwood J, Wagstaff M, et al. Use of Biodegradable Temporising Matrix (BTM) in the reconstruction of diabetic foot wounds: A pilot study. Scars, Burns & Healing. 2022;8:20595131221122272.
  52. 52. Sandora N, Fitria NA, Kusuma TR, Winarno GA, Tanjunga SF, Wardhana A. Amnion bilayer for dressing and graft replacement for delayed grafting of full-thickness burns; A study in a rat model. Plos one. 2022;17(1):e0262007.
  53. 53. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nature biotechnology. 2014;32(8):773-85.
  54. 54. Liu P, Shen H, Zhi Y, Si J, Shi J, Guo L, et al. 3D bioprinting and in vitro study of bilayered membranous construct with human cells-laden alginate/gelatin composite hydrogels. Colloids and Surfaces B: Biointerfaces. 2019;181:1026-34.
  55. 55. Intini C, Elviri L, Cabral J, Mros S, Bergonzi C, Bianchera A, et al. 3D-printed chitosan-based scaffolds: An in vitro study of human skin cell growth and an in-vivo wound healing evaluation in experimental diabetes in rats. Carbohydrate polymers. 2018;199:593-602.
  56. 56. Chang P, Li S, Sun Q, Guo K, Wang H, Li S, et al. Large full-thickness wounded skin regeneration using 3D-printed elastic scaffold with minimal functional unit of skin. Journal of Tissue Engineering. 2022;13:20417314211063022.
  57. 57. Fortier JL, Castiglione CL, Guo L. Skin Grafting. Interventional Treatment of Wounds: A Modern Approach for Better Outcomes. 2018:123-42.
  58. 58. Serra R, Rizzuto A, Rossi A, Perri P, Barbetta A, Abdalla K, et al. Skin grafting for the treatment of chronic leg ulcers–a systematic review in evidence‐based medicine. International wound journal. 2017;14(1):149-57.
  59. 59. Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. Bioengineered skin substitutes for the management of burns: a systematic review. Burns. 2007;33(8):946-57.
  60. 60. Wardhana A, Valeria M. Tissue engineering and regenerative medicine: A Review. Jurnal Plastik Rekonstruksi. 2020;7(1):10-7.
  61. 61. Melman L, Jenkins E, Hamilton N, Bender L, Brodt M, Deeken C, et al. Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair. Hernia. 2011;15:157-64.
  62. 62. Godoi MM, Reis EM, Koepp J, Ferreira J. Perspective from developers: Tissue-engineered products for skin wound healing. International Journal of Pharmaceutics. 2024:124319.
  63. 63. Chen F-M, Liu X. Advancing biomaterials of human origin for tissue engineering. Progress in polymer science. 2016;53:86-168.
  64. 64. Burke JF, Yannas IV, Quinby Jr WC, Bondoc CC, Jung WK. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Annals of surgery. 1981;194(4):413.
  65. 65. Noordenbos J, Doré C, Hansbrough JF. Safety and efficacy of TransCyte* for the treatment of partial-thickness burns. Journal of Burn Care & Rehabilitation. 1999;20(4):275-81.
  66. 66. Marston WA, Hanft J, Norwood P, Pollak R, Group DDFUS. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes care. 2003;26(6):1701-5.
  67. 67. Pourmoussa A, Gardner DJ, Johnson MB, Wong AK. An update and review of cell-based wound dressings and their integration into clinical practice. Annals of translational medicine. 2016;4(23).
  68. 68. Ouyang Q-Q, Hu Z, Lin Z-P, Quan W-Y, Deng Y-F, Li S-D, et al. Chitosan hydrogel in combination with marine peptides from tilapia for burns healing. International journal of biological macromolecules. 2018;112:1191-8.
  69. 69. Hashemi S-S, Mohammadi A-A, Kian M, Rafati A, Ghaedi M, Ghafari B. Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury. Iranian Journal of Basic Medical Sciences. 2024;27(2):223.
PDF

Keywords

  • Artificial skin
  • Biomaterials
  • 3-D scaffold
  • Skin substitute
  • Full-thickness burn

Author Information

Normalina Sandora

Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. 3Universitas Prima Indonesia, Faculty of Medicine, Medan, Indonesia, Indonesia.

Email: normalinasandora@gmail.com

ORCID : https://orcid.org/0000-0002-2332-9605

Nur Amalina Fitria

Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, Indonesia.

Email: nur.amalinafitria2@gmail.com

ORCID : https://orcid.org/0000-0001-8163-9604

Aditya Wardhana

Plastic Reconstructive and Aesthetic Division, Department of Surgery, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta,, Indonesia., Indonesia.

Email: aditya_wrdn@yahoo.com

ORCID : https://orcid.org/0000-0002-7577-8357

Nandita Melati Putri

Plastic Reconstructive and Aesthetic Department of Surgery, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia., Indonesia.

Email: nandita.putri@ui.ac.id

ORCID : https://orcid.org/0000-0003-0839-7877

Akhmad Noviandi Syarif

Plastic Reconstructive and Aesthetic Division, Department of Surgery, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia., Indonesia.

Email: akhmad.noviandi01@ui.ac.id

ORCID : https://orcid.org/0000-0001-9708-8915

Tyas Rahmah Kusuma

Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Indonesia.

Email: tyas.r.kusuma@gmail.com

ORCID : https://orcid.org/0009-0006-3663-2781

Benati Karimah

Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Indonesia.

Email: benati.karimah@gmail.com

ORCID : https://orcid.org/0009-0003-9870-999X

Article History

Submitted : 30 July 2025
Revised : 30 July 2025
Published : 29 September 2025

How to Cite This

Sandora, N., Amalina Fitria, N., Wardhana, A., Melati Putri , N., Noviandi Syarif , A., Rahmah Kusuma, T., & Karimah, B. (2025). Current Updates of Biomaterials for Skin Replacement: A Systematic Review. Jurnal Plastik Rekonstruksi, 12(2), 97–108. https://doi.org/10.14228/jprjournal.v12i2.45

Crossmark and Dimension

Verify authenticity via CrossMark

Share This Article

Copyright & License

Authors retain the copyright of the article and grant Jurnal Plastik Rekonstruksi the right of first publication with the work simultaneously licensed under a Creative Commons Attribution License. Articles opting for open access will be immediately available and permanently free for everyone to read, download and share from the time of publication.

This work is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Open Access Statement

Jurnal Plastik Rekonstruksi is an open access journal. This journal provides immediate open access to every article on the principle that making research freely accessible to the public; It supports a greater global exchange of knowledge; and an invaluable way to boost the visibility and impact of research.

This also means that Jurnal Plastik Rekonstruksi it's free availability on the public Internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than that inseparable from gaining access to the Internet itself.

Journal Info

Profile Image
Editor-in-Chief: dr. Narottama Tunjung, Sp.B.P.R.E., F.L.
Frequency: 2 issues per year (March & September)
National Accreditation: Sinta 3
Email: info@jprjournal.com

Video Article

Multistages Aesthetic Refinement Post Anterolateral Thigh Free Flap in Head and Neck Reconstruction

Atmodiwirjo P, Ramadan MR, Triatmoko SE, Arina MN. Multistages Aesthetic Refinement Post Anterolateral Thigh Free Flap in Head and Neck Reconstruction. J Plast Rekons 2020;7(1):38-42. DOI: https://doi.org/10.14228/jpr.v7i1.298

How to Harvest The Radial Forearm Free Flap

Atmodiwirjo P, Ramadan MR, Triatmoko SE, Ralena NA. How to Harvest Radial Forearm Free Flap. J Plast Rekons 2020;7(1):7-9. DOI: https://doi.org/10.14228/jpr.v7i1.296  

ACCREDITATION

Since October 2020, Jurnal Plastik Rekonstruksi has received Accreditation from the Ministry of Technology Research / National Research and Innovation Agency (SINTA 3)

https://sinta.ristekbrin.go.id/journals/detail?id=2054

Indexed by:

   

.    

custom_header

ISSN : 2089-6492
Online ISSN : 2089-9734
Publisher: The Lingkar Studi Bedah Plastik Foundation and is the official journal of Plastic Reconstructive and Aesthetic Surgery Residency Program, Faculty of Medicine, Universitas Indonesia.

Current Issue