From microparticles to bulk hydrogels: emerging granular hydrogels in cartilage tissue engineering

Abstract

Articular cartilage exhibits a limited capacity for self-repair, prompting extensive research into advanced biomaterials that can support tissue regeneration. Among these, injectable hydrogels have gained attention for their minimally invasive delivery and suitability for bioprinting applications. However, conventional nanoporous bulk hydrogels often lack the necessary microporosity and architectural complexity to fully support effective tissue regeneration. To overcome these shortcomings, recent innovations have turned toward granular hydrogels—injectable materials fabricated by dense packing of hydrogel microparticles into cohesive, microporous bulk hydrogels. These granular systems offer improved injectability, superior microporosity, and the ability to form heterogeneous bioinks/injectables that better replicate the natural extracellular matrix, thereby promoting more efficient regeneration. This review delves into the advancements in granular hydrogel technology, with a focus on the fabrication of hydrogel microparticles and the jamming strategies used to assemble them into granular injectables/bioinks. It further explores their potential in cartilage tissue repair, emphasizing the benefits of such emerging microporous bulk assemblies in minimally invasive procedures (MIPs) or as smart bioinks for fabricating patient specific implants. Finally, the review outlines key opportunities and challenges in translating these innovative materials into clinical applications, highlighting the growing promise of granular hydrogels in addressing current limitations in cartilage regeneration.