Multifunctional porous poly (L-lactic acid) nanofiber membranes with enhanced anti-inflammation, angiogenesis and antibacterial properties for diabetic wound healing

Abstract

With increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.

Poly(Propylene Carbonate)-Based Biodegradable and Environment-Friendly Materials for Biomedical Applications

“…For example, polylactic acid (PLA), a hydrophobic and thermally stable aliphatic polyester that biodegrades into non-toxic natural lactic acid, has been widely used in biomedical applications. PLA can be used alone or in combination with other small molecules or polymers for cartilage and joint regeneration [ 24 , 25 ], drug delivery and release [ 26 , 27 ], wound healing [ 28 , 29 ] and other therapies [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Other biodegradable polymers, including poly(lactide-co-glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), poly(ε-caprolactone) (PCL), poly(glycolic acid) (PGA), poly(3-hydroxybutyrate) (PHB), poly(ethylene glycol) (PEG) and PPC ( Figure 1 ) [ 37 , 38 , 39 ], have also been applied in healthcare.…”

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing

“…In vitro cell testing results demonstrated that the PLA/SCS/PDA-GS membrane could immunomodulate macrophages toward M2 phenotype development. Moreover, the PLA nanofiber membrane containing SCS also exhibited an enhanced potential for promoting macrophage-to-fibroblast transdifferentiation [ 215 ].…”

“…Gentamicin was loaded into the middle hydrogel layer, exerting its antibacterial activity through natural release, while the outer nanofiber layers of the hydrogel act as diffusion barriers, reducing the initial burst release of gentamicin (15–30%) [ 234 ]. Hao Yu et al modified poly(L-lactic acid) (PLA) porous nanofiber membranes by incorporating polydopamine–gentamicin (PDA-GS) and sulfated chitosan (SCS), promoting the controlled release of GS through dopamine self-polymerization to prevent early wound infection [ 215 ].…”

Innovative Functional Biomaterials as Therapeutic Wound Dressings for Chronic Diabetic Foot Ulcers

“…PLA is an aliphatic polyester that is easily obtained in an eco-friendly way through the condensation of lactic acid, followed by the ring-opening polymerization of cyclic lactides [ 68 , 118 , 136 , 137 ]. Its good biocompatibility, biodegradability, and relatively high mechanical properties make PLA an appealing material for biomedical applications [ 68 , 118 , 119 ].…”