Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia

Abstract

Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.

Advancements and Applications of Injectable Hydrogel Composites in Biomedical Research and Therapy

“…In a separate study, the therapeutic potential of an injectable hydrogel composed of nano-sized suspended formulations of human fibroblast-derived matrix (sFDM) is explored. This hydrogel demonstrates excellent biocompatibility, mechanical stability, and regenerative effects, effectively promoting wound healing, neovessel formation, and reducing necrosis and fibrosis in preclinical models [148].…”

“…Promotes neovessel formation, collagen deposition, blood reperfusion, and reduces necrosis and fibrosis in cutaneous wound and hindlimb ischemia models [148] Self-assembling hydrogels based on thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs)…”

“…Hydrogels with controlled release capabilities and biocompatibility have demonstrated effectiveness in diabetic wound repair [135,138,142,147]. Various hydrogel formulations have been developed to promote wound healing, tissue regeneration, and control infections [28,136,140,141,147,148]. Antibacterial hydrogels have shown efficacy in inhibiting bacterial growth and managing drug-resistant infections [137,144,145,149].…”