Exosome-Loaded Thermoresponsive Hydrogels for Tissue Regeneration: Design Principles, Delivery Mechanisms, and Translational Challenges Publisher



Esmaeili E ; Rad I ; Soflaei S ; Bansal P ; Sharma C ; Nematov O ; Sapaev I
Source: Journal of Polymers and the Environment Published:2026

Abstract

The functional regeneration of complex tissues remains a significant challenge in clinical medicine. While exosomes have emerged as potent, cell-free therapeutic agents capable of orchestrating immunomodulation, angiogenesis, and stem cell recruitment, their clinical translation is severely limited by poor pharmacokinetics, including rapid clearance, enzymatic degradation, and off-target distribution. This review elucidates the strategic integration of exosomes with thermosensitive hydrogels as an innovative delivery platform to overcome these barriers. We detail how injectable, thermosensitive polymers—selected for their tunable sol-gel transition at physiological temperatures—form a protective depot that ensures high local retention and provides sustained spatiotemporal release of exosome cargo. The polymer selection rationale is discussed, balancing biocompatibility, degradation kinetics, and emerging considerations of environmental sustainability, including the use of biodegradable natural polymers (e.g., chitosan, hyaluronic acid) and renewable sourcing strategies that minimize ecological footprint. The article critically analyzes methods for exosome isolation, loading strategies into hydrogel matrices, and essential characterization techniques to ensure vesicle integrity and predict in vivo performance. Furthermore, we highlight the compelling therapeutic efficacy of this synergistic platform across diverse regenerative applications, including bone and cartilage repair, wound healing, and neuroregeneration, demonstrating enhanced outcomes compared to free exosomes. We discuss future perspectives on manufacturing scalability, the development of innovative stimuli-responsive systems, the integration of life-cycle assessment into material design, and the translational pathway toward clinical adoption. The convergence of exosome biology and advanced biomaterial engineering represents a paradigm shift in regenerative medicine, offering a powerful, off-the-shelf strategy for restoring functional tissue while ensuring environmental responsibility. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.