The Use of Hydrogel Microspheres As Cell and Drug Delivery Carriers for Bone, Cartilage, and Soft Tissue Regeneration

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.