Four‐Arm Polymer‐Guided Formation of Curcumin‐Loaded Flower‐Like Porous Microspheres as Injectable Cell Carriers for Diabetic Wound Healing

Abstract

AbstractStem cell injection is an effective approach for treating diabetic wounds; however, shear stress during injections can negatively affect their stemness and cell growth. Cell‐laden porous microspheres can provide shelter for bone mesenchymal stem cells (BMSC). Herein, curcumin‐loaded flower‐like porous microspheres (CFPM) are designed by combining phase inversion emulsification with thermally induced phase separation‐guided four‐arm poly (l‐lactic acid) (B‐PLLA). Notably, the CFPM shows a well‐defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of ‐BMSC and curcumin. The BMSC‐carrying CFPM (BMSC@CFPM) maintains the proliferation, retention, and stemness of ‐BMSCs, which, in combination with their sustainable curcumin release, facilitates the endogenous production of growth/proangiogenic factors and offers a local anti‐inflammatory function. An in vivo bioluminescence assay demonstrates that BMSC@CFPM can significantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, could significantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction, and M2 macrophage polarization. RNA sequencing further unveils the mechanisms by which BMSC@CFPM promotes diabetic wound healing by increasing ‐growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing.