Advances in polymer-based hydrogel systems for adipose-derived mesenchymal stem cells toward bone regeneration

Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies. Adipose-derived mesenchymal stem cells (AD-MSCs) have garnered significant interest in bone tissue engineering (BTE) because of their abundant availability, minimally invasive harvesting procedures, and robust differentiation potential into osteogenic lineages. Unlike bone marrow-derived mesenchymal stem cells, AD-MSCs can be easily obtained in large quantities, making them appealing alternatives for therapeutic applications. This review explores hydrogels containing polymers, such as chitosan, collagen, gelatin, and hyaluronic acid, and their composites, tailored for BTE, and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs. Various hydrogel fabrication techniques and biocompatibility assessments are discussed, along with innovative modifications to enhance osteogenesis. This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement, such as direct encapsulation and three-dimensional bioprinting. We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels, including osteoinduction, vascularization, and extracellular matrix remodeling. We also review the preclinical and clinical applications of AD-MSC-hydrogel systems, emphasizing their success and limitations. In this review, we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.