Tissue Engineering and Vascularization Strategies for Skin Reconstruction

Skin reconstruction via tissue engineering aims to replicate the complex structure and function of native skin, restoring barrier integrity, sensation and appendage formation. Native skin comprises a stratified epidermis, a collagen-rich dermis and a dense vascular network that supplies oxygen and nutrients. Conventional autografting remains the clinical gold standard but is limited by donor-site morbidity and availability. Engineered skin substitutes seek to overcome these obstacles by integrating biomaterial scaffolds, cell populations and bioactive cues to guide regeneration. A primary challenge lies in achieving rapid and functional vascularization of thick constructs to prevent necrosis and enhance integration. Strategies under investigation include scaffold design with controlled porosity and stiffness, incorporation of angiogenic growth factors or gene vectors, prevascularization of constructs with endothelial cells or microvascular fragments, hypoxic conditioning to stimulate pro-angiogenic secretomes, and advanced fabrication methods such as three-dimensional bioprinting and microfluidic patterning. These approaches aim not only to accelerate neovascular ingrowth but also to recreate skin appendages and immunological competence, with applications ranging from burn coverage to management of chronic ulcers and congenital defects.

Research from Nature Portfolio

Recent studies have advanced the engineering of fully functional skin grafts by harnessing developmental and cell-competition mechanisms. One approach generated complete chimeric skin in vivo by combining pluripotent stem cell-derived keratinocytes with embryonic dermis, yielding grafts that contain hair follicles and sweat glands and that engraft with efficacy comparable to autologous transplants. Another investigation demonstrated that medium conditioned by dermal fibroblasts under hypoxic culture markedly enhances proliferation of endothelial cells and drives the formation of extensive, organised capillary-like networks within fibrin gels, offering a cost-effective route to prevascularise constructs. A seminal report described a scaffold-free three-dimensional skin substitute produced via layer-by-layer cell coating, in which dermal fibroblasts, endothelial cells and keratinocytes self-assemble into preformed microvessels; upon implantation, these vessels inosculate with host circulation within seven days, markedly improving graft survival and wound closure.

Tissue Engineering and Vascularization Strategies for Skin Reconstruction publication trend

The graph below shows the total number of articles in tissue engineering and vascularization strategies for skin reconstruction across all publications each year (not limited to Nature Index journals).

Technical terms

Tissue-engineered skin substitute: A biofabricated construct combining cells, biomaterials and bioactive factors to replicate skin structure and function for grafting.

Vascularization: The development and integration of blood vessels within a graft, ensuring adequate perfusion and nutrient delivery.

Angiogenesis: The process by which new capillaries sprout from existing vasculature, essential for graft survival.

Prevascularization: The in vitro assembly of microvascular networks within a scaffold prior to implantation to promote rapid inosculation.

3D bioprinting: A layer-by-layer additive manufacturing technique for depositing cells and biomaterials to recreate complex tissue architectures.

Extracellular matrix (ECM): A network of proteins and polysaccharides that provides structural support and biochemical signalling to resident cells.

References

1. Skin graft with dermis and appendages generated in vivo by cell competition. Nature Communications (2024).
2. Conditioned medium produced by fibroblasts cultured in low oxygen pressure allows the formation of highly structured capillary-like networks in fibrin gels. Scientific Reports (2020).
3. In Vitro Construction of Scaffold‐Free Bilayered Tissue‐Engineered Skin Containing Capillary Networks. BioMed Research International (2013).
4. Prevascularization of dermal substitutes with adipose tissue-derived microvascular fragments enhances early skin grafting. Scientific Reports (2018).
5. 3D-Printed Gelatin Methacrylate Scaffolds with Controlled Architecture and Stiffness Modulate the Fibroblast Phenotype towards Dermal Regeneration. Polymers (2021).
6. Breathing new life into tissue engineering: exploring cutting-edge vascularization strategies for skin substitutes. Angiogenesis (2024).
7. Bioengineered Skin Substitutes: Advances and Future Trends. Applied Sciences (2021).