Injectable, electrosprayed RGD-coupled alginate hydrogel microcapsules enable enhanced viability and sustained...

The clinical translation of mesenchymal stem cell (MSC) therapies remains limited due to rapid cell clearance and stress-induced viability loss during injection. These limitations emphasize the need to develop delivery systems allowing MSCs to persist in the tissue and exert their biological effect. Cell microencapsulation within alginate (Alg) biomaterials is a promising strategy, where arginine-glycine-aspartic acid (RGD)-coupled alginate (RAlg) hydrogels have recently demonstrated improved bioactivity. However, achieving precise encapsulation and injectability while preserving cell viability remains an ongoing challenge. This study presents an injectable delivery platform using electrosprayed RAlg microcapsules that enhance viability and sustain the release of MSCs. Electrospray parameters were optimized to yield a microcapsule size of 175.4 ± 21.1 μm with high uniformity and consistent spherical morphology. Electron microscopy images of the microcapsules revealed a highly ordered microporous architecture. Physicochemical characterization confirmed that the presence of RGD peptides did not significantly alter the swelling, viscoelasticity, and encapsulation efficiency of Alg. Successful encapsulation of MSCs were observed, with cells assuming a round morphology within the microcapsule. After 14 days, RAlg maintained significantly higher cell viability at 91.3% than Alg alone (84.9%). Furthermore, a time-dependent release of cells was observed, with intact microcapsules at day 1, partial degradation with 59-61% cell release at day 7, and extensive degradation with 78-81% release by day 14. Both RAlg and Alg had comparable release performance. Overall, this study demonstrates the potential of electrosprayed RAlg microcapsules as a biocompatible and injectable platform for the sustained delivery of viable MSCs in regenerative medicine applications.