PLCL/PCL Dressings with Platelet Lysate and Growth Factors Embedded in Fibrin for Chronic Wound Regeneration

Abstract

Introduction The formation of diabetic ulcers (DU) is a common complication for diabetic patients resulting in serious chronic wounds. There is therefore, an urgent need for complex treatment of this problem. This study examines a bioactive wound dressing of a biodegradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) covered by a thin fibrin layer for sustained delivery of bioactive molecules. Methods Electrospun PLCL/PCL nanofibers were coated with fibrin-based coating prepared by a controlled technique and enriched with human platelet lysate (hPL), fibroblast growth factor 2 (FGF), and vascular endothelial growth factor (VEGF). The coating was characterized by scanning electron microscopy and fluorescent microscopy. Protein content and its release rate and the effect on human saphenous vein endothelial cells (HSVEC) were evaluated. Results The highest protein amount is achieved by the coating of PLCL/PCL with a fibrin mesh containing 20% v/v hPL (NF20). The fibrin coating serves as an excellent scaffold to accumulate bioactive molecules from hPL such as PDGF-BB, fibronectin (Fn), and α-2 antiplasmin. The NF20 coating shows both fast and a sustained release of the attached bioactive molecules (Fn, VEGF, FGF). The dressing significantly increases the viability of human saphenous vein endothelial cells (HSVECs) cultivated on a collagen-based wound model. The exogenous addition of FGF and VEGF during the coating procedure further increases the HSVECs viability. In addition, the presence of α-2 antiplasmin significantly stabilizes the fibrin mesh and prevents its cleavage by plasmin. Discussion The NF20 coating supplemented with FGF and VEGF provides a promising wound dressing for the complex treatment of DU. The incorporation of various bioactive molecules from hPL and growth factors has great potential to support the healing processes by providing appropriate stimuli in the chronic wound.

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing

“…The advantages of the coating method include simple operation, ease of achieving a uniform drug distribution on the scaffold surface, the ability to load multiple drugs for combined therapeutic effects, and the ability to regulate the drug loading and release rate by adjusting factors such as the drug solution concentration and coating method [ 194 ]. However, due to the weak binding between the drug and the scaffold in the coating method, the drug release rate may be too fast, which is not conducive to achieving sustained and controlled release [ 195 ]. It is worth mentioning that the physisorption method is more suitable for small molecules, where the drug is attached to the scaffold by van der Waals forces, whereas the encapsulation method is more suitable for large molecules (e.g., proteins), which mainly involves trapping the drug molecules within the pores of the material [ 196 , 197 , 198 ].…”

“…Vascular endothelial growth factor (VEGF) is the most common growth factor incorporated into nanofiber scaffolds for the promotion of angiogenesis [ 185 ]. Other growth factors, such as fibroblast growth factor (FGF) [ 195 ], platelet-derived growth factor (PDGF) [ 225 ], and transforming growth factor-β (TGF-β) [ 226 ], can also synergistically promote angiogenesis. Some cytokines, such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) [ 227 , 228 ], can induce endothelial cell migration and proliferation, thereby promoting angiogenesis.…”

Electrospun Nanofiber Membranes with Various Structures for Wound Dressing

“…In the wound healing model, the NFM showed a 96.39 ± 0.66% wound healing rate, and the promoting effect of growth factors on wound healing was demonstrated. Taborska et al [122] used poly(L-lactide-co-ε-caprolactone)/PCL nanofibers as a matrix containing human platelet lysates (hPL), and the fibrin network of VEGF and FGF as a coating to prepare a composite wound dressing. The results showed that the fibrin network was a good receptacle for bioactive molecules, and the sustained release of growth factors and hPL from the coating significantly increased the survival rate of human saphenous vein endothelial cells in collagen wound models.…”