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REVIEW
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Hydrogel microspheres for bone regeneration through regulation of the regenerative microenvironment

Pengrui Zhang1 ,  Qiwei Qin1 ,  Xinna Cao1 ,  Honglin Xiang1 ,  Dechao Feng2 ,  Dilinaer Wusiman3 ,  Yuling Li*
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1 Department of Orthopaedics, Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
2 Division of Surgery & Interventional Science, University College London, London, UK
3 Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
BMT 2024 , 5(3), 205–235; https://doi.org/10.12336/biomatertransl.2024.03.002
Submitted: 27 June 2024 | Revised: 12 August 2024 | Accepted: 13 September 2024 | Published: 28 September 2024
Copyright © 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Bone defects are a prevalent category of skeletal tissue disorders in clinical practice, with a range of pathogenic factors and frequently suboptimal clinical treatment effects. In bone regeneration of bone defects, the bone regeneration microenvironment—composed of physiological, chemical, and physical components—is the core element that dynamically coordinates to promote bone regeneration. In recent years, medical biomaterials with bioactivity and functional tunability have been widely researched upon and applied in the fields of tissue replacement/regeneration, and remodelling of organ structure and function. The biomaterial treatment system based on the comprehensive regulation strategy of bone regeneration microenvironment is expected to solve the clinical problem of bone defect. Hydrogel microspheres (HMS) possess a highly specific surface area and porosity, an easily adjustable physical structure, and high encapsulation efficiency for drugs and stem cells. They can serve as highly efficient carriers for bioactive factors, gene agents, and stem cells, showing potential advantages in the comprehensive regulation of bone regeneration microenvironment to enhance bone regeneration. This review aims to clarify the components of the bone regeneration microenvironment, the application of HMS in bone regeneration, and the associated mechanisms. It also discusses various preparation materials and methods of HMS and their applications in bone tissue engineering. Furthermore, it elaborates on the relevant mechanisms by which HMS regulates the physiological, chemical, and physical microenvironment in bone regeneration to achieve bone regeneration. Finally, we discuss the future prospects of the HMS system application for comprehensive regulation of bone regeneration microenvironment, to provide novel perspectives for the research and application of HMS in the bone tissue engineering field.

Keywords
bone regeneration
bone tissue engineering
hydrogel microspheres
regeneration microenvironment
Funding
This work is supported by the National Natural Science Foundation of China (Nos. 82102578, 82472404), Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province (No. 2023ZYD0071), China Postdoctoral Science Foundation (No. 2022M720603), National Natural Science Foundation of Sichuan (No. 2024NSFSC0678), Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0104), Research Project of Health Commission of Sichuan Province (No. 2023-1601), Research Project of Nanchong Science and Technology Bureau (Nos. 22SXJCQN0004, 22SXQT0308), and Research Project of the Affiliated Hospital of North Sichuan Medical College (Nos. 2023ZD002, 2023-2ZD001).
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Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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