Repairing bone defects resulting from trauma, tumor resection, or pathological conditions remains a significant clinical challenge. While conventional bone grafting techniques are constrained by inherent limitations, stem cell-based tissue engineering scaffolds offer a promising therapeutic alternative. The ideal scaffold should not only serve as a structural support but, more importantly, must establish a bioactive microenvironment capable of directing stem cell osteogenic differentiation. Consequently, scaffold biofunctionalization has emerged as a fundamental strategy for achieving effective bone regeneration. This review comprehensively examines the primary materials utilized in bone regeneration scaffolds and systematically analyzes key biofunctionalization approaches, including surface modification, incorporation of bioactive molecules, and integration of functional ions. Moreover, it thoroughly discusses the mechanisms through which biofunctionalized scaffolds modulate stem cell behavior and enhance bone repair in vivo. Finally, the article provides insights into future research directions and emerging trends, aiming to inform the rational design and development of advanced bone regeneration scaffolds.

Mesenchymal stem cells (MSCs) have shown significant potential in bone regeneration and regenerative medicine in recent years. With the advancement of tissue engineering, MSCs have been increasingly applied in bone repair and regeneration, and their clinical application potential has grown through interdisciplinary approaches involving biomaterials and genetic engineering. However, there is a lack of systematic reviews summarizing their applications in bone regeneration. To address this gap, we analyzed the latest research on MSCs for bone regeneration published from 2013 to 2023. Using the Web of Science Core Collection, we conducted a literature search in December 2024 and employed bibliometric tools like CiteSpace and VOSviewer for a comprehensive analysis of the key research trends. Our findings focus on the development of cell engineering, highlighting the advantages, limitations, and future prospects of MSC applications in bone regeneration. These insights aim to enhance understanding of MSC-based bone regeneration, inspire new research directions, and facilitate the clinical translation of MSC research.

Bone defects remain a significant clinical challenge due to the limited regenerative capacity. Biomaterials can offer effective therapeutic approaches to a