Design and tissue engineering applications of microporous annealed particle (MAP) scaffolds

Microporous annealed particle (MAP) scaffolds are emerging as a facile, yet sophisticated biomaterial platform with tremendous potential for tissue regenerative applications. These scaffolds are fabricated in situ through interparticle crosslinking of microgels using a variety of covalent or non-covalent techniques and possess excellent tunability and biocompatibility. The microporous structure of MAP scaffolds allows cellular infiltration and vascularization independent of degradation rate, making them more advantageous than traditional nanoporous bulk hydrogels. Moreover, the incorporation of in situ crosslinking allows MAP scaffolds to retain the key advantages of traditional microgel-based scaffolds-such as injectability and modularity-while providing the added benefit of a fixed packing configuration at the delivery site, enhancing structural integrity and cellular integration. In addition, their properties, such as stiffness, porosity, and composition, can be tailored to precisely modulate cell behavior, making them versatile tools to enhance therapeutic outcomes in various tissue engineering applications, such as cardiac, soft tissue, bone, and cartilage reconstruction. In this review, we explore the design of MAP scaffolds and their use for tissue engineering. We describe the fundamentals of MAP scaffold design, elucidate the fabrication techniques used to make microgel building blocks, highlight current applications in various tissue engineering contexts, and discuss emerging trends in MAP scaffold development. STATEMENT OF SIGNIFICANCE: Microporous annealed particle (MAP) scaffolds are emerging as a versatile and potent biomaterial delivery platform that incorporates the advantages of granular and bulk hydrogels to enhance cell integration and improve therapeutic outcomes in regenerative medicine. Due to their tremendous potential, MAP scaffolds have rapidly gained traction across a variety of tissue engineering context, from bone and cartilage regeneration to neural tissue repair. This review outlines advances in MAP scaffold design, highlighting the influence of polymer selection, annealing chemistry, and microstructural features on scaffold properties. The use of MAP scaffolds in multiple regenerative medicine contexts is then surveyed. Lastly, emerging trends are identified and guide is provided for future innovation in MAP scaffold development for regenerative medicine.