Elastic porous microspheres/extracellular matrix hydrogel injectable composites releasing dual bio-factors enable tissue regeneration

Yi Li, Siyang Liu, Jingjing Zhang, Yumeng Wang, Hongjiang Lu, Yuexi Zhang, Guangzhou Song, Fanhua Niu, Yufan Shen, Adam C. Midgley, Wen Li (), Deling Kong () and Meifeng Zhu ()
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Yi Li: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Siyang Liu: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Jingjing Zhang: Chifeng Municipal Hospital
Yumeng Wang: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Hongjiang Lu: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Yuexi Zhang: The Third Affiliated Hospital of Wenzhou Medical University
Guangzhou Song: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Fanhua Niu: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Yufan Shen: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Adam C. Midgley: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Wen Li: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Deling Kong: State Key Laboratory of Medicinal Chemical Biology, Nankai University
Meifeng Zhu: State Key Laboratory of Medicinal Chemical Biology, Nankai University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Injectable biomaterials have garnered increasing attention for their potential and beneficial applications in minimally invasive surgical procedures and tissue regeneration. Extracellular matrix (ECM) hydrogels and porous synthetic polymer microspheres can be prepared for injectable administration to achieve in situ tissue regeneration. However, the rapid degradation of ECM hydrogels and the poor injectability and biological inertness of most polymeric microspheres limit their pro-regenerative capabilities. Here, we develop a biomaterial system consisting of elastic porous poly(l-lactide-co-ε-caprolactone) (PLCL) microspheres mixed with ECM hydrogels as injectable composites with interleukin-4 (IL-4) and insulin-like growth factor-1 (IGF-1) dual-release functionality. The developed multifunctional composites have favorable injectability and biocompatibility, and regulate the behavior of macrophages and myogenic cells following injection into muscle tissue. The elicited promotive effects on tissue regeneration are evidenced by enhanced neomusle formation, vascularization, and neuralization at 2-months post-implantation in a male rat model of volumetric muscle loss. Our developed system provides a promising strategy for engineering bioactive injectable composites that demonstrates desirable properties for clinical use and holds translational potential for application as a minimally invasive and pro-regenerative implant material in multiple types of surgical procedures.

Date: 2024
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DOI: 10.1038/s41467-024-45764-4

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