Preparation And Application Of Electrospun Radially Oriented Nanofiber Hydrogel Dressin

Chronic wounds are one type of hard-healing deseases in clinics.They commonly possess some unquie characteristics,including high incidence,long course of disease,and high cost of treatment.In recent years,with the in-depth study of chronic wound healing,the design and development of advanced dressing materials with multifunctional features has attracted much attention.Among numerous dressing materials,electrospun nanofiber materials are recognized as prospective dressing candidates,due to their high surface area,high porosity,and small pore size,as well as excellent extracellular matrix(ECM)fibril-mimicking characteristics.In addition,hydrogel dressings present exellent exudate-absorbing ability,which not only provide instructive moist microenvironment for wound healing,but also effectively solved the adhesion between wound and dressing materials.Based these mentioned merits,the hydrogel materials have also been widely designed and utlized to treat skin wounds.In this thesis,A combination of electrospinning technique and photocrosslinking hydrogel-forming stragety was employed to generate an innovative multifunctional dressing materials made from electrospun radially-oriented nanofiber mat and drugloaded hydrogel compound,which are expected to exhibit execellent healing capacities on the diabetic chronic wounds.(1)Firstly,methacrylated gelatin(MeGel)was synthesized through the methacryloyl substitution of commercial gelatin(Gel),and the effects of MeGel concentration on the photocrosslinking gelatinization were investigated.The results showed that the MeGel crosslinked hydrogels presented higher mechanical properties,but lower swelling and degradation properties with increasing the MeGel content.The electrospinnability of MeGel polymer was also explored.It was found that,the electrospun MeGel nanofibers exbited higher nanofiber diamters when the MeGel content increased.Unfortunately,all the as-prepared MeGel nanofiber mats possessed inferior mechanical properties and poor structural stability.To address the above-mentioned issue,poly(L-lacticacid)(PLLA)was introduced and blended with MeGel for the fabrication of electrospun nanofiber mats,and how the MeGel/PLLA mass ratio affected the performances of finally-generated nanofiber mats were sysmatically explored.The results displayed that the electrospun nanofiber mats with higher PLLA content exhibited significantly improved mechanics,but notaby decreased biocompatibility,swelling and degradation properties.Moreover,all the MeGel-contained nanofiber mats had excellent hydrophilicity.Balancing all the properties,the MeGel / PLLA nanofiber mats prepared from the mass ratio of 1:1 were choosen for the subsequent experiments.(2)Then,a modified electrospinning device was designed to improve the mat structure of electropsun nanofibers.Specifically,the 1:1 MeGel / PLLA blend was electrospun into radially-oriented nanofiber mats by using our innovative setup,and the same polymeric blend was electrospun into randomly-oriented nanofiber mats and uniaxially-oriented nanofiber mats by using two classical electrospinning devices.The effects of mat structure on water absorption capacity,mechanical properties,degradation rate,and biocompatibility of electrospun MeGel/PLLA nanofibers were sysmatically investigated.It was found that the different mat structure had no obvious influences on fiber diameter,water absorption,degradation rate and air permeability,showed significant effects on mechanics.Importantly,the radially-oriented structure was demonstrated to be a more appropriate nanofiber pattern for effectively guiding migration and promoting proliferation of human dermal fibroblasts(HDFs)throughout providing the cell recruitment and regulation abilities compared with the conventional randomly-oriented structure and uniaxially-oriented structure.Moreover,the radiallyoriented MeGel/PLLA nanofiber mats could significantly improve the wound healing rate of mouse acute wounds compared with both randomly-oriented and uniaxiallyoriented MeGel/PLLA nanofiber mats.(3)Eventually,novel compound dressings were constructed by crosslinking one layer of bioactive MeGel hydrogel on the top of electrospun MeGel/PLLA radiallyaligned nanofiber mats.Considering the pathological complexity of diabetic wound site,the Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound(i.e.,SRHC)with different concentrations were loaded into the hydrogel layer to improve the biofunctionability of compound dressings.The effects of SRHC concentration on the properties of the compound dressing and the treatment effects of diabetic chronic woundswere explored in depth.It was found that SRHC loading has no obvious effects on the mechanics,swelling properties and biocompatibility of obtained compound dressings,but the addition of SRHC could significantly increased the antibacterial,antiinflammation,angiogenesis and healing-promoting properties of as-prepared compound dressings.In addition,all the compound dressings with and without SRHC showed excellent hemostatic properties.It should be noticed that SRHC loaded compound dressings could significantly accelerate the high-quality regeneration and healing of diabetic wounds by effectively reducing the inflammation,promoting the vascularization,and facilitating the regeneration of hair follicles.Specifically,the high SRHC loaded compound dressings presented a high healing area of 97.4±2.8 % at day18 after surgery.Our present study indicated that the SRHC contained compound dressings show great potential for the treatment of hard-healing diabetic wounds.