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REVIEW
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The use of hydrogel microspheres as cell and drug delivery carriers for bone, cartilage, and soft tissue regeneration

Chung-Hsun Lin1,2 ,  Jesse R. Srioudom1 ,  Wei Sun3 ,  Malcolm Xing4 ,  Su Yan1 ,  Le Yu1,5,* ,  Jian Yang6,7,*
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1 Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA
2 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
3 Leicester International Institute, Dalian University of Technology, Panjin, Liaoning Province, China
4 Department of Mechanical Engineering, University of Manitoba, Winnipeg, Canada
5 Division of Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, MO, USA
6 Biomedical Engineering Program, Westlake University, Hangzhou, Zhejiang Province, China
7 Research Centre for Industries of the Future, Westlake University, Hangzhou, Zhejiang Province, China
BMT 2024 , 5(3), 236–256; https://doi.org/10.12336/biomatertransl.2024.03.003
Submitted: 12 July 2024 | Revised: 22 August 2024 | Accepted: 12 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, cartilage, and soft tissue regeneration is a complex process involving many cellular activities across various cell types. Autografts remain the “gold standard” for the regeneration of these tissues. However, the use of autografts is associated with many disadvantages, including donor scarcity, the requirement of multiple surgeries, and the risk of infection. The development of tissue engineering techniques opens new avenues for enhanced tissue regeneration. Nowadays, the expectations of tissue engineering scaffolds have gone beyond merely providing physical support for cell attachment. Ideal scaffolds should also provide biological cues to actively boost tissue regeneration. As a new type of injectable biomaterial, hydrogel microspheres have been increasingly recognised as promising therapeutic carriers for the local delivery of cells and drugs to enhance tissue regeneration. Compared to traditional tissue engineering scaffolds and bulk hydrogel, hydrogel microspheres possess distinct advantages, including less invasive delivery, larger surface area, higher transparency for visualisation, and greater flexibility for functionalisation. Herein, we review the materials characteristics of hydrogel microspheres and compare their fabrication approaches, including microfluidics, batch emulsion, electrohydrodynamic spraying, lithography, and mechanical fragmentation. Additionally, based on the different requirements for bone, cartilage, nerve, skin, and muscle tissue regeneration, we summarize the applications of hydrogel microspheres as cell and drug delivery carriers for the regeneration of these tissues. Overall, hydrogel microspheres are regarded as effective therapeutic delivery carriers to enhance tissue regeneration in regenerative medicine. However, significant effort is required before hydrogel microspheres become widely accepted as commercial products for clinical use.

Keywords
drug delivery
fabrication techniques
hydrogel microspheres
microgels
tissue regeneration
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