Development of a Novel Pre-Vascularized Three-Dimensional Skin Substitute Using Blood Plasma Gel

Abstract

Skin substitutes with existing vascularization are in great demand for the repair of full-thickness skin defects. In the present study, we hypothesized that a pre-vascularized skin substitute can potentially promote wound healing. Novel three-dimensional (3D) skin substitutes were prepared by seeding a mixture of human endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium chloride formed gel scaffold, and seeding keratinocytes onto the surface of the plasma gel. The capacity of the EPCs to differentiate into a vascular-like tubular structure was evaluated using immunohistochemistry analysis and WST-8 assay. Experimental studies in mouse full-thickness skin wound models showed that the pre-vascularized gel scaffold significantly accelerated wound healing 7 days after surgery, and resembled normal skin structures after 14 days post-surgery. Histological analysis revealed that pre-vascularized gel scaffolds were well integrated in the host skin, resulting in the vascularization of both the epidermis and dermis in the wound area. Moreover, mechanical strength analysis demonstrated that the healed wound following the implantation of the pre-vascularized gel scaffolds exhibited good tensile strength. Taken together, this novel pre-vascularized human plasma gel scaffold has great potential in skin tissue engineering.

Development and Evaluation of Biomimetic 3D Coated Composite Scaffold for Application as Skin Substitutes

“…In the composite scaffold group, the tensile strength and strain at break of the composite scaffold were 7.8 MPa and 71%. These data were within the reference range and higher than those of many previous studies of relevant skin scaffolds, [ 16,28,56 ] indicating that the composite scaffolds have appropriate mechanical properties for tissue regeneration. Moreover, the composite scaffold exhibited a remarkable improvement of strain at break and tensile strength in comparison with the samples fabricated by the EHD jetting or electrospinning.…”

A novel strategy to engineer pre-vascularized 3-dimensional skin substitutes to achieve efficient, functional engraftment

“…Fibroblast-derived ECM components are essential for vascular formation and cell migration, adhesion, differentiation, and proliferation 21 . Recently, vascularization of skin constructs has been studied by seeding and cultivating vessel-forming cells on scaffolds 6,9,22,23 . FN-G coating of the cell surface by LbL assembly, which promotes cell-to-cell interaction and homogeneous stacking, is critical to the fabrication of the scaffold-free 3D-tissues 12 .…”

Current and Future Perspectives on Skin Tissue Engineering: Key Features of Biomedical Research, Translational Assessment, and Clinical Application

“…Incorporation of melanocytes (for desired skin pigmentation and color), adipose derived stem cells and adipocytes (for adipose tissue development), and endothelial cells (for vascularization) are currently active areas of research and poised to have a significant impact on the final outcome of tissue engineered skin scaffolds. The promise of advanced skin tissue regeneration to facilitate wound repair or in vitro model development relies on the successful application of such multicellular, multimaterial bioink.…”