Biofunctionalization of Stem Cell Scaffold for Osteogenesis and Bone Regeneration

Abstract

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.

Keywords: biofunctionalization; bone regeneration; scaffold; stem cell; visualization research.

Figure 3

Research Findings Related to Peptide Segment and Nucleic Acid Aptamer Modifications. (A) Double staining with Runx2 and OPN immunofluorescence in hMSCs cultured on skeletal tissue for 14 days [112]. (B) Reconstructed micro-CT images of bone samples cultured on skeletal tissue [112]. The dashed red circles indicate the original extent of the critical-sized calvarial defect. (C) Representative images of crystal violet-stained migrating cells [115]. (D) Representative images of SO/FG staining after various treatments over 3 weeks. Scale bar: 250 μm, n = 5 per group [115]. (E) Representative images of alizarin red S staining for mineral deposits in BMSCs in bone-like medium. Scale bar: 200 μm, n = 3 per group [115].

Figure 1

Mechanisms of MSC-mediated bone regeneration. MSCs promote bone repair through osteogenic differentiation, paracrine secretion of bioactive factors, and immunomodulation that will be beneficial for regeneration. Created with BioRender.com.

Figure 2

Classification of scaffold materials. The outer ring indicates the material sources, with each sector representing a category and containing the corresponding materials. Created with BioRender.com.

Figure 4

Global Literature Trend. (A) Annual publication volume and cumulative publication volume globally in this field. (B) Top 10 countries or regions in terms of total citations in the field. (C) The percentage of publications by country in this field. (D) Top 10 countries and regions in terms of H-index in the field of mesenchymal stem cell therapy for bone regeneration.

Figure 5

Bibliometric Analysis of Cooperation Among Authors, Countries, and Institutions. (A) Mapping of the identified authors in this field based on VOSviewer. (B) National collaboration analysis and (C) Institutional collaboration analysis in this field.