Construction And Evaluation Of PLGAm/CCS Dermal Scaffold

Objective:To develop a well-supported dermal sbustitute by combining technical textile technologies with conventional tissue engineering approaches, and evaluate its effect on tissue regeneration and wound healing.Methods:Good biocompatibility, excellent mechanical strength, and optimal three-dimensional (3D) microstructure are the three basic characteristics in the ideal tissue-engineered scaffolds. For dermal substitutes, scaffolds are artificial equivalents of natural extracellular matrices (ECM) used to induce tissue regeneration or replace damaged tissues/organs. Therefore, the selection of biomaterials and the fabrication methods are crucial for the construction of scaffolds for tissue engineering. Biological materials such as collagen, fibroin, gelatin, alginate, and elastin have been used extensively to prepare tissue-engineered scaffolds with better biocompatibility, biodegradation, and lower antigenicity, but these scaffolds lack sufficient mechanical properties to accommodate the biomechanical environment. Recently, scaffold mechanical properties have been paid more attention than before. However, most porous biomaterials fabricated from amorphous polymers cannot withstand suturing because of their poor mechanical strength.Knitting is an ancient and fresh technique with a history of no less than 1,000 years. The initiation and development of tissue engineering and regenerative medicine provide a potential opportunity for knitting. Many knitted meshes from synthetic or biological materials have been designed and applied alone to strengthen the frail tissues of the body, or in combination with other kinds of biomaterials to repair or replace damaged tissues/organs. Especially for the latter, the primary results demonstrated that hybrid scaffolds reinforced by knitted mesh possess excellent mechanical properties and could more effectively promote tissue repair, ligament/tendon/cartilage regeneration, pipe-like organ reconstruction, etc. However, the in vivo influence of this kind of hybrid scaffold on inductive regeneration and angiogenesis has not been investigated in skin regeneration.In this study, a warp-knitted poly(L-lactide-co-glycolide) (PLGA) mesh was fabricated with a Tricot machine. The in vitro and in vivo experiments were carried out to investigate the physical properties biodegradability, and biocompatibility of the knitted PLGA mesh. The results demonstrated that the PLGA mesh possessed the typical warp-knitted structures, excellent mechanical properties, suitable degradation ratio and good biocompatibility, and showed a possible potential to be employed as a "skeleton" for improving the mechanical strength of collagen-based dermal substitutes in tissue engineering. In order to verify the above hypothesis, a hybrid dermal substitute was developed by incorporating the knitted PLGA mesh into collagen-chitosan scaffolds (CCS) to prepare PLGA knitted mesh-reinforced CCS (PLGAm/CCS). The morphologies, water absorption capacity and mechanical strength in dry and wet state of PLGAm/CCS were investigated in vitro. To characterize the tissue response, especially angiogenesis and tissue regeneration, PLGAm/CCS was embedded subcutaneously in SD rats, compared with two control implants, i.e. PLGA mesh (PLGAm) and CCS. At week 1,2,4 and 8 postsurgery, tissue specimens were harvested for histology, immunohistochemistry, immunofluorescence, real-time quantitative PCR (RT-qPCR and western blotting analysis. The results illustrated that the incorporation of PLG knitted mesh into CCS can improve the mechanical properties and water absorption capacity with little influence on its three dimensional (3D) porous microstructure. Aftr implantation, PLGAm/CCS can resist the contraction and promote cell infiltratio, neotissue formation and blood vessel ingrowth especially from its mesh side. Then Could the PLGAm/CCS be used as a dermal substitute to repair full-thickness skin defects and improve the healing quality? The full-thickness skin defects of SD rats wre successfully repaired by one-step transplantation of PLGAm/CCS and autologus split-thickness skin. The results indicated that PLGAm/CCS can inhibit won contraction, promote dermal reconstruction more efficiently than CCS. Conclusions:(1) PLGAm/CCS possessing good biocompatibility and excellent mechaial properties, efficiently inducing tissue regeneration and promoting angiogenesis,has a promising and practical potential as a dermal substitute. (2) Mechanical properties of scaffolds are important for inducing tissue regeneration and vascularisation by maintaining 3D microstructure.