Electrospun Chitosan/Polycaprolactone Nanofibrous Membranes For Skin Wound Repair

The skin plays a vital role in maintaining the health of the human body.Wound defect is one of the most common clinical conditions.And bacterial infection is the main cause of impediments to wound healing.Therefore,it is essential to develop a multifunctional wound dressing that inhibits bacterial infection,improves wound healing and promotes tissue regeneration.Electrospun fibrous membranes,mimicing the natural extracellular matrix,have been widely used in the field of skin tissue engineering.Thus,series of fibrous membranes with antibacterial functions were constructed in this study by electrospun technology.Firstly,a bilayer composite fibrous membrane based on polycaprolactone（PCL）,chitosan（CS）and zinc oxide（Zn O）nanoparticles was prepared by coaxial electrospinning technique.The outer layer was consisted of PCL random microfibers loading with Zn O nanoparticles,giving the bilayer membrane good antibacterial activity.The inner fibrous membrane was composed of aligned CS fibers,which performed anti-inflammatory effects and induced directional cell alignment.It was found that both the inner CS aligned fibers and the outer PCL fibers had good fibers morphology and the fibers were approximately1200 nm and 800 nm,respectively.And the diameter of the inhibition zone of the composite membrane loading with 1.2wt%Zn O nanoparticles was approximately 12.8 mm against E.coli and 13.4 mm for S.aureus,respectively.In addition,the prepared bilayer fibrous membrane could maintain the bioactivity of Zn O nanoparticles efficiently.The combination of Zn O nanoparticles and CS aligned fibers synergistically reduced inflammation and promote cell migration and re-epithelialization in vivo.In order to improve the antibacterial effect of the CS/PCL fibrous membranes,fibrous membranes loading with ciprofloxacin（Cip）were prepared by coaxial electrospinning to optimise the orientation structure and size of CS/PCL fibres and to promote the migration and alignment of fibroblasts.It was shown that the average diameter of Cip-loaded CS/PCL fibres was about 300 nm.And CS/PCL membranes loading with 2.0wt%Cip showed significant inhibition zone than CS/PCL against E.coil and S.aureus,with diameters of34.8 mm and 50.2 mm,respectively.With the increasing of the Cip content,the inhibition rate increased,while the cytocompatibility of the fibrous membrane gradually decreased.The CS/PCL membrane loading with 2.0wt%Cip was selected for in vivo animal investigations,taking into account the compatibility and antibacterial capabilities of fibrous membranes.It was found that the CS/PCL membrane loading with 2.0wt%Cip accelerated the wound healing process.To improve the anti-inflammation property of the PCL/CS membranes,PCL/CS fibrous membranes loading with Cip and zinc ions(Zn²⁺)were prepared by coaxial electrospinning.The prepared membrane could exert anti-bactericidal and anti-inflammatory effect,as well as regulated the arrangement of fibroblasts,thus promoted the wound healing.Antibacterial tests demonstrated that the fibrous membranes loading with Cip and Zn²⁺showed significantly higher inhibition zones for E.coil and S.aureus,with diameters of 21.7 mm and 21.4 mm,respectively.And the results of in vitro inflammation evaluation experiments showed that the fibrous membrane loading with Zn²⁺significantly reduced the expression levels of IL-6 and TNF-α.In vivo transplantation experiments verified the pro-healing effect of the fibrous membranes on whole skin wounds in mice.In summary,a series of new fibrous membranes were constructed with antibacterial functions by electrospun technology.The physical structure,antibacterial properties,cellular activity and in vivo wound healing ability of the fiber dressings were systematically tested in this work.The developed multifunctional CS/PCL fibrous membrane loading with Cip and Zn²⁺hold a great potential to be applied in the field of skin wound dressings.