Preparation And Properties Of Injectable PLGA Short Fiber-Hydrogel Wound Dressing

Skin injury harms human health,and even threatens life.At present,various wound dressings have been developed to expedite the repair of skin wounds.Among them,hydrogel dressings became increasingly popular owing to excellent biocompatibility,wound exudate absorption properties,and moisture retention characteristics.Unfortunately,the conventional hydrogel dressings are in the form of sheets,and they should be prepared in advance,resulting in imperfect coverage of irregular wounds and incomplete filling of the deep wounds.Therefore,the in-situ formed dressings bring breakthroughs for treating irregular wounds.However,in-situ formed hydrogel dressings suffer from poor mechanical properties,long gelatin time,and lack of natural extracellular matrix(ECM)-like structure.Herein,we developed a hydrogel-based system incorporated with highly dispersed chemical-modified electrospun fiber segments.A double crosslinking network composed of polymer-polymer and polymer-fiber was formed in the hydrogel.The obtained short fiber-incorporated hydrogel showed ECM-like structure,injectability,in-situ forming capability,and improved mechanical property.The details are summarized as follows:(1)To obtain the stable precursor solution of short fiber-hydrogel,the poly(lactic-co-glycolic acid)(PLGA)fibers were prepared by electrospinning,and the amino-modified PLGA(APLGA)short fibers were fabricated through the aminolysis treatment followed by homogenizing.The water contact angle test showed that the surface of the pristine PLGA membrane was hydrophobic with a water contact angle(WCA)of 134.6°.In contrast,the APLGA membrane exhibited a WCA of 19.5°,indicating that the PLGA membrane surface became hydrophilic after aminolysis treatment.Meanwhile,compare with the PLGA short fibers with a fiber length of 81.8 μm,APLGA short fibers showed a shorter length(22.2 μm)with a more uniform length distribution.In addition,the APLGA short fibers dispersed in aqueous precursor solution stably and uniformly.(2)We developed an amino-modified APLGA short fiber-hydrogel composite based on gelatin methacrylate(GM)and oxidized dextran(ODex).Different from the physical blending method used in traditional micro/nano particle incorporated hydrogels,the APLGA fiber segments were utilized both as fillers as well as the crosslinking agents where Schiff-base reaction occurred between APLGA short fiber and ODex chains,leading to faster gelling.The double crosslinking network composed of dynamic bonds between short fibers and hydrogel and photo-crosslinked GM in the main hydrogel,contributed to the rapid gelation of the hydrogel.As shown in SEM images,compare with the PLGA fiber-hydrogel,the APLGA fiber-hydrogel composites showed more uniform porous structure with the presence of short fibers.Moreover,the compressive strength of GM/ODexAPLGA hydrogels was 3.5 times of that of GM/ODex hydrogel without short fibers,indicating that the addition of APLGA short fibers which acted as reinforcing fillers and crosslinkers enhanced the mechanical performance.(3)From the perspective of practical application,the in vitro cell culture and in vivo wound healing study were performed.The L929 fibroblasts were cultured on the GM/ODex-APLGA short fiber-hydrogel composites.The GM/ODex-APLGA hydrogels showed good cell viability,proliferation and infiltration.In addition,in vivo study demonstrated a positive effect on the repair of rat full-thickness skin wounds,indicating great potential as a wound dressing.In summary,an injectable in-situ forming hydrogel was developed by introducing aminomodified PLGA electrospun fiber segments into the GM/ODex hydrogel.The homogenously distributed short fiber as fillers,in combination with double crosslinking networks composed of dynamic bonds between short fibers and hydrogel and photo-crosslinked GM in the main hydrogel,contributed to the improved mechanical properties.Also,the GM/ODex-APLGA short fiberhydrogel composites could mimic the ECM structure.The short fiber-hydrogel composites promoted wound closure and tissue healing.This study provided reference values for the design and construction of fiber-hydrogel composites.