Novel bi-layered dressing patches constructed with radially-oriented nanofibrous pattern and herbal compound-loaded hydrogel for accelerated diabetic wound healing

Abstract

The clinical treatment of chronic wounds caused by different pathophysiological ulcers like diabetic ulcers still remains a bottleneck. Although numerous approaches have been designed and developed, their therapeutic effects cannot meet the medical needs due to the complicated pathological microenvironment and restricted regenerative capacity of hard-healing chronic wounds. In this study, novel bi-layered and multifunctional dressing patches constructed with one layer of electrospun methacrylated gelatin (MeGel)/poly (L-lactic acid) (PLLA) radially-oriented nanofiber mats (RNMs) and one layer of Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC)-loaded MeGel hydrogel were designed to promote the closure and healing of diabetic wounds. An innovative electrospinning method was firstly designed and implemented to generate MeGel/PLLA RNMs, which were demonstrated to be a more appropriate nanofiber pattern for effectively guiding migration and promoting proliferation of human dermal fibroblasts (HDFs) compared with the conventional electrospun MeGel/PLLA haphazardly-oriented nanofiber mats (HNMs) and MeGel/PLLA uniaxially-oriented nanofiber mats (UNMs). Importantly, the in vivo mice acute full-thickness defect models also confirmed that MeGel/PLLA RNMs could significantly promote the cell migration and accelerate the healing rate throughout providing the cell recruitment and regulation abilities in comparison with MeGel/PLLA HNMs and UNMs. The MeGel hydrogel precursors loaded with different concentrations of SRHC were employed to generate the hydrogel layers on the MeGel/PLLA RNMs, and therefore a series of bi-layered wound dressing patches with integrated multifunctional properties were fabricated. All the bi-layered wound dressing patches with or without SRHC showed excellent hemostatic performances. The bi-layered dressing patches containing SRHC exhibited great antibacterial property to both E. coli and S. aureus, and also high cell survival rate to HDFs. For the in vivo full-thickness diabetic wound healing test, the bi-layered dressing patches without SRHC exhibited a faster wound healing rate compared with the medical gauzes. Furthermore, the 10% SRHC loaded bi-layered dressing patches significantly accelerated 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 10% SRHC loaded bi-layered dressing patches presented a high healing area of 97.4 ± 2.8% at day 18 after surgery. Our present study demonstrated that the SRHC contained bi-layered dressing patches show great potential for the treatment of hard-healing diabetic wounds.