Injectable microcarrier‐hydrogel composite for dental stem cell delivery and tissue regeneration

Conventional methods of stem cell therapy for tissue regeneration often face challenges, such as poor cell viability and integration posttransplantation. To address this, we proposed transplanting cells within synthetic microenvironments that maintain viability, cell phenotype, support extracellular matrix (ECM) secretion, and promote differentiation to enhance the regeneration of damaged host tissue. This hypothesis was tested in dental tissue regeneration using dental pulp stem cell‐laden microcarriers (MCs) mixed in a gelatin methacrylate (GelMA) hydrogel as a delivery system. The combination of MCs and GelMA exhibited similar physical properties and favorable biological properties compared to GelMA alone. Specifically, cell‐laden MC mixed into GelMA enhanced cell proliferation and ECM secretion and maintained a normal phenotype. Notably, MC‐modified GelMA amplified odontogenic differentiation, mineralization, and vascular endothelial growth factor release. Moreover, the storage of MC‐modified GelMA showed no detrimental effects on its injection force, cell viability, and mineralization potential, which demonstrates that the composite hydrogel is a promising injectable vehicle for therapeutic stem cell delivery. This strategy may be broadly applied to various tissues and organ systems, in which the provision and instruction of a cell population to participate in regeneration may be clinically useful. Current approaches to tissue regeneration carry the risk of cell death, often caused by poor cell attachment and graft loss. By transplanting cells within specially designed synthetic microenvironments, we can maintain cell health, support the secretion of important extracellular matrix components, and enhance differentiation to aid the repair of damaged tissues, and this was proven in the context of dental pulp tissue regeneration.