Immunoregulation in Skull Defect Repair with a Smart Hydrogel Loaded with Mesoporous Bioactive Glasses

Author:

Yuan Shiguo12,Zheng Boyuan3,Zheng Kai12,Lai Zhiheng12,Chen Zihang4,Zhao Jing5,Li Shaoping5,Zheng Xiaofei3ORCID,Wu Peng6,Wang Huajun3

Affiliation:

1. Department of Orthopaedic, Hainan Traditional Chinese Medicine Hospital, Hainan Medical University, Haikou, 571924, China.

2. Department of Orthopaedic, Guangdong Provincial Hospital of Chinese Medicine, Hainan Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510388, China.

3. Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, 510630, China.

4. Department of Psychology, Li Ka Shing Faculty of Medicine, State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, 999077, China.

5. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau SAR, 519000, China.

6. Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Abstract

Skull defect repair is a complex and critical medical challenge, and there is an urgent need to develop multifunctional tissue engineering scaffolds for skull regeneration. The success of bone tissue engineering depends on the construction of scaffolds that can regulate the immune microenvironment of bone regeneration and mimic the liquid crystal and viscoelastic properties of natural bone extracellular matrix. Hence, a smart hydrogel (PEGDA5/AM15/CLC-BMP-4@MBG) with good biocompatibility and the ability to modulate the wound immune microenvironment has been developed for the repair of skull defects. The hydrogel consists of chitin liquid crystal hydrogel (PEGDA5/AM15/CLC) and mesoporous bioactive glasses (MBGs) loaded with bone morphogenetic protein-4 (BMP-4). The liquid crystal hydrogel not only offers the necessary biological support and mechanical properties but also maintains the stability of the liquid crystal state, facilitating adhesion and regeneration of surrounding bone tissue. In addition, BMP-4@MBG intelligently regulates the release rate of BMP-4 in response to changes in wound microenvironment, thus effectively promoting the transformation of macrophages from M1 to M2 macrophages. At the same time, Ca 2+ and Si 4+ released by MBG degradation and BMP-4 synergically promote bone repair process. The PEGDA5/AM15/CLC-BMP-4@MBG hydrogel shows excellent immunomodulatory and osteogenic properties of bone microenvironment and is a promising scaffold material for bone tissue engineering.

Funder

Hainan Province Clinical Medical Center

the National Key Research and Development Program of China

Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University, China

Natural Science Foundation of Guangdong Province

National Natural Science Foundation of China

Science and Technology Projects in Guangzhou

the Fundamental Research Funds for the Central Universities

Publisher

American Association for the Advancement of Science (AAAS)

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