Multifunctional Injectable Hydrogel Microparticles Loaded with miR-29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis.

The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.

Hyaluronic Acid-Based Reactive Oxygen Species-Responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing.

Diabetic wounds are more likely to develop into complex and severe chronic wounds. The objective of this study is to develop and assess a reactive oxygen species (ROS)-responsive multifunctional injectable hydrogel for the purpose of diabetic wound healing. A multifunctional hydrogel (HA@Cur@Ag) is successfully synthesized with dual antioxidant, antibacterial, and anti-inflammatory properties by crosslinking thiol hyaluronic acid (SH-HA) and disulfide-bonded hyperbranched polyethylene glycol (HB-PBHE) through Michael addition; while, incorporating curcumin liposomes and silver nanoparticles (AgNPs). The HA@Cur@Ag hydrogel exhibits favorable biocompatibility, degradability, and injectivity. The outcomes of in vitro and in vivo experiments demonstrate that the hydrogel can effectively be loaded with and release curcumin liposomes, as well as silver ions, thereby facilitating diabetic wound healing through multiple mechanisms, including ROS scavenging, bactericidal activity, anti-inflammatory effects, and the promotion of angiogenesis. Transcriptome sequencing reveals that the HA@Cur@Ag hydrogel effectively suppresses the activation of the tumour necrosis factor (TNF)/nuclear factor κB (NF-κB) pathway to ameliorate oxidative stress and inflammation in diabetic wounds. These findings suggest that this ROS-responsive multifunctional injectable hydrogel, which possesses the ability to precisely coordinate and integrate intricate biological and molecular processes involved in wound healing, exhibits notable potential for expediting diabetic wound healing.