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Novel Bioprinting Strategy Provides for Rapid and Precise Wound Healing

Review of “In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds” from Scientific Reports by Stuart P. Atkinson

The limitations inherent to split thickness autografts and allografts for severe wound treatment have fostered the development of alternative approaches, including dermal substitutes and tissue-engineered complex biological skin equivalents. Recently, cellular therapy-based strategies, which employ manually seeded matrices or cell spraying methods [1-3], have been explored as a means to rapidly and precisely cover wounds with epidermal keratinocytes and dermal fibroblasts to promote accelerated healing and improved cosmetic outcomes [4, 5]. 

Unfortunately, current seeding and spraying technologies prevent the accurate delivery of specific cell types to the required target sites, inhibiting the generation of complex skin structures; therefore, a research team headed by Sean V. Murphy (Wake Forest School of Medicine, Winston-Salem, NC, USA) developed a novel bioprinting-based approach to mitigate these hurdles [6]. In their recent Scientific Reports study, Albanna at al. describe the design and proof-of-concept validation of an innovative mobile skin bioprinting system that integrates wound imaging with precise in-situ delivery of skin cell types to accelerate the formation of skin with typical structure and function and enhance wound healing [7].

The authors employed a bioprinting system displaying multiple advantages over previous systems including portability, accuracy in the identification and measurement of wound sizes and topologies through a hand-held three-dimensional wound scanner, facile sterilization, and ease of operation and maintenance. Furthermore, bioprinting employed the delivery of multiple cell types through a cartridge-based delivery system similar to that employed in traditional inkjet printing, thereby facilitating the correct spatial orientation of cells tailored to an individual wound according to models generated from the three-dimensional scans.

Initial proof-of-concept studies in a full-thickness wound mouse model demonstrated that this newly developed bioprinting strategy permitted the rapid and precise coverage of wounds through the direct delivery of a bilayer of human dermal fibroblasts and epidermal keratinocytes in a manner that replicated the layered structure of healthy skin. Encouragingly, the authors reported no mortality, wound infection, or significant skin irritation and the rapid closure of the wound over six weeks when compared to control mice. 

Next, the authors moved to validation in a porcine full-thickness skin wound model, a more human-like skin model, discovering that bioprinting of autologous cells within a biological hydrogel facilitated the rapid and precise coverage of wounds that accelerated wound closure, increased epithelialization, and reduced wound contraction when compared to other treatments. Overall, the regenerated skin tissue displayed a dermal structure and composition similar to healthy mature skin, including extensive vascularization and the presence of proliferating keratinocytes.

The authors now hope to examine long-term skin function and cosmetic results and perform suitable long-term cell tracking experiments to assess the full contribution of exogenously applied cells following bioprinting with their newly developed system. Furthermore, they hope to experiment with additional biomaterials and cell types (e.g.,  melanocytes, adipose cells, and hair follicle cells) to further accelerate wound healing, generate skin with improved functional and cosmetic outcomes, develop an off-the-shelf system that can be applied to rapidly treat patients, and explore applications in other wounds types (such as burns, ulcers, and deep tissue injuries).

For more on bioprinting and novel skin wound healing strategies, stay tuned to the Stem Cells Portal!

References

  1. Hansbrough JF, Boyce ST, Cooper ML, et al., Burn Wound Closure With Cultured Autologous Keratinocytes and Fibroblasts Attached to a Collagen-Glycosaminoglycan Substrate. JAMA 1989;262:2125-2130.
  2. Kirsner RS, Marston WA, Snyder RJ, et al., Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. The Lancet 2012;380:977-985.
  3. Wood FM, Kolybaba ML, and Allen P, The use of cultured epithelial autograft in the treatment of major burn injuries: A critical review of the literature. Burns 2006;32:395-401.
  4. Navarro FA, Stoner ML, Park CS, et al., Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model. Journal of Burn Care & Rehabilitation 2000;21:513-8.
  5. Gravante G, Di Fede MC, Araco 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;33:966-972.
  6. Murphy SV and Atala A, 3D bioprinting of tissues and organs. Nature Biotechnology 2014;32:773.
  7. Albanna M, Binder KW, Murphy SV, et al., In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Scientific Reports 2019;9:1856.