Bionic Functionalization Of Poly (Lactic-co-Glycolic Acid) For Skin Wound Repair

Patients with skin injury caused by various reasons,such as accidents,working and daily life,diseases and other human activities are increasing annually.Medical dressings are usually used in wound repair to accelerate and promote the healing of skin wounds.To this end,some characteristics are necessary for the ideal wound dressings,which include good biocompatibility,in vivo biodegradability,reasonable mechanical properties,antibacterial activity and the ability to induce cell and tissue growth.The materials for wound dressing mainly consist of two groups: natural materials(cellulose,chitosan,alginate,collagen,etc.)and synthetic materials(polylactic acid(PLA),polyvinyl alcohol(PVA),polycaprolactone(PCL),poly(lactic-co-glycolic acid(PLGA),etc.).Natural materials can be obtained from a wide range of sources,but only limited modification of the active groups on the surface can be done on these natural materials Synthetic materials can be designed and prepared according to the physical and chemical properties required by the dressing.Hence,synthetic dressing material with good biodegradability,mechanical properties,biocompatibility and processing properties can be obtained.However,various growth factors participate in the process of skin repair,regulating cell growth and differentiation at various stages,and are indispensable in the process of wound healing.Yet,the ability of both natural and synthetic materials to induce and promote the growth of cells and tissues remains weak.Meanwhile,deep and extensive skin injury often causes bacterial infection.Failure to remove bacteria from the wound site in a timely manner poses a risk of difficult healing.Therefore,some bioactive factors and antibacterial agents should be introduced to the dressing to endow mutltiple functions.Among many synthetic polymers,PLGA has the advantages of good biocompatibility,desirable biodegradability and excellent processing performance.The degradation rate of PLGA can be controled by changing the ratio of lactic acid and glycolic acid in the polymerization.Therefore,PLGA has been widely used as drug carriers and tissue engineering scaffolds,and has been approved by the US FDA.Therefore,PLGA is an ideal material for the preparation of skin wound repair dressings.In this study,based on the approach of molecular bionics and inspired by the adhesion protein from mussel,we have introduced a DOPA motif into bFGF and PonG1 by genetic engineering.Meanwhile,an electrospun PLGA film has been prepared by patterned electrospinning as the substrate of the dressings.In order to achieve the effect of promoting cell adhesion and vascularization,as well as antibacterial property,DOPA-modified fibroblast growth factor(bFGF)and antibacterial peptide(PonG1)have been supplemented to the dressing.DOPA-modified bFGF and PonG1 can bind to the surface of the base material of the dressings.Hence,a wound dressing with the ability to promote cell adhesion and proliferation as well as antibacterial activity has been prepared for the application of wound repair.In this study,the chemical composition and mechanical properties of wound dressings have been characterized by the methods of scanning electron microscopy(SEM),atomic force microscopy(AFM),Fourier-transformed infrared(FTIR),contact angle measurment,mechanical testing.The binding and releasing ability of DOPAbFGF and DOPA-PonG1 within PLGA film has also been investgated in vitro.Cell adhesion and proliferation experiments have been used to evaluate the biocompatibility of the obtained wound dressing.Expression levels of collagen I(COL-I)and vascular endothelial growth factor(VEGF)have been measuered for cells growing on the dressing.The antibacterial activity of the dressing has been examined with two strains of bacterias,E.coli and S.aureus.The results have shown that DOPA-bFGF and DOPAPonG1 can be deposited on the surface of the electrospun fibers and the surface roughness has been increased.FTIR results show that there are large amounts of DOPAbFGF and DOPA-PonG1 bound to pattened electrospun PLGA membrane via biomimetic adhesion.The contact angle measurement exhibits that the hydrophilicity of the patterned electrospun membrane has also been enhanced after the modification with DOPA-bFGF and DOPA-PonG1.The mechanical testing results show that the patterned electrospun film has higher tensile strength than the disordered counterparts.The antibacterial experiment has demonstrated that the antibacterial activity has been improved for the DOPA-PonG1 group.The cell experiments show that the proliferation of cells and the gene expressions of COL-I and VEGF have been significantly enhanced after introducing DOPA-bFGF to the surface of the patterned electrospun membrane.The wound repair ability of the bio-inspired wound dressing has been verified in the full-skin wound model of rats,where the electrospun membranes of various groups have been applied as wound dressings,and the wound healing of different groups has been observed from Day 1 to Day 14.The results have shown that the wound healing rates of the groups with DOPA-bFGF are significantly higher than those of other groups at Day 7.At Day 14,the above trend is even more obvious,indicating that the bio-inspired adhesion of DOPA-bFGF plays a significant role in wound healing,especially with the synergestic effect of DOPA-PonG1.In comparison with the groups of commercial chitosan quaternary ammonium salt dressings and alginate dressings,we has found that the effect of DOPA-bFGF/DOPAPonG1@PLGA dressing is significantly better than commercial dressing groups.In conclusion,electrospinning has been used to prepare a patterned electrospun PLGA fiber membrane.Through the approach of molecular bionics,two kinds of bioactive factors DOPA-bFGF and DOPA-PonG1 have been introduced to the patterned electrospun PLGA membrane via the adhersion of DOPA motif.Subsequently,the antibacterial activity and the ability to promote cell growth has been verified in vitro for the pattened electrospun PLGA membrane decorated with DOPA-bFGF and DOPAPonG1.Moreover,it has also been demonstrated in vivo that the PLGA dressing with DOPA-bFGF and DOPA-PonG1 can accelerate the wound healing in the full-skin wound model of rats.