Introduction: Bone and cartilage defects pose significant clinical challenges due to limited self-healing ability. MSCs provide a versatile cell source capable of osteogenic and chondrogenic differentiation. When combined with biocompatible scaffolds and bioactive molecules, MSC-based tissue engineering offers an effective strategy for functional tissue repair. Recent innovations include the incorporation of nanomaterials, the development of smart scaffolds responsive to environmental stimuli, and precise 3D bioprinting methods that enhance cell distribution and scaffold architecture
Methods: A systematic review was conducted of peer-reviewed articles from 2018 to 2025 sourced from PubMed, Scopus, and Web of Science databases. Studies reporting quantitative and qualitative outcomes on MSC-based scaffolds for bone and cartilage regeneration were included. Key parameters analyzed were alkaline phosphatase (ALP) activity, osteogenic/chondrogenic gene expression, defect fill percentages in animal models, and histological evaluations. Comparative analysis highlighted trends in scaffold materials, bioprinting technologies, and growth factor delivery
Results: Several key studies from 2018 to 2025 demonstrated significant advancements in MSC-based tissue engineering for bone and cartilage regeneration:
Lee et al. (2018) reported a 35% increase in bone defect fill in rabbits using calcium phosphate scaffolds combined with bone marrow MSCs. The newly formed bone exhibited organized structure and active osteoblasts.
Wang et al. (2018) observed a twofold increase in COL2A1 gene expression and formation of hyaline-like cartilage matrix when adipose-derived MSCs were treated with TGF-β1.
Kim et al. (2019) showed a 40% increase in alkaline phosphatase (ALP) activity and uniform mineralized matrix development in human MSCs seeded on PLLA nanofiber scaffolds.
Singh et al. (2019) achieved 50% cartilage defect repair in mice with chitosan-hydroxyapatite scaffolds and observed reduced local inflammation.
Pereira et al. (2020) found a fourfold increase in ALP activity and upregulated osteogenic gene expression (Runx2, Osteocalcin) using natural polymer-nano-hydroxyapatite composite scaffolds.
Smith et al. (2021) reported up to 75% bone defect fill with chitosan/nano-hydroxyapatite scaffolds seeded with MSCs in a rabbit model.
Chen et al. (2022) demonstrated a twofold increase in collagen type II and glycoprotein expression in alginate hydrogels with adipose MSCs, indicating high-quality cartilage formation.
Patel et al. (2023) developed a BMP-2 controlled-release system that enhanced bone defect fill by 45%, supporting sustained cellular stimulation.
Wang et al. (2024) utilized 3D bioprinting to fabricate scaffolds with uniform porosity, achieving a 35% increase in ALP activity and defect fill.
Zhang et al. (2025) improved cell migration and scaffold mechanical strength by 30% through advanced 3D bioprinting methods.
Overall, these studies demonstrated enhanced osteogenic and chondrogenic differentiation, improved extracellular matrix production, and effective defect healing in various animal models
Conclusion: he reviewed studies clearly indicate that combining MSCs with advanced biomaterial scaffolds and innovative technologies such as 3D bioprinting and controlled growth factor delivery significantly improves tissue regeneration outcomes. Nanomaterial incorporation, especially nano-hydroxyapatite, enhances the osteoinductive properties of scaffolds, stimulating greater ALP activity and upregulation of osteogenic genes, which translates into stronger and more organized bone tissue formation.
Similarly, controlled release of growth factors like TGF-β1 and BMP-2 supports targeted differentiation and matrix maturation, as shown by increased collagen II and mineralized matrix deposition. 3D bioprinting enables precise control of scaffold architecture and cell distribution, which enhances nutrient diffusion, cell migration, and mechanical integrity of the constructs.
Despite these promising preclinical results, significant challenges remain for clinical translation. Standardizing scaffold fabrication, ensuring reproducible cell sources, and verifying long-term safety and efficacy in human trials are critical steps yet to be fully addressed. Furthermore, integration of newer cell sources, such as iPSC-derived MSCs, and development of smart scaffolds capable of dynamic responses to physiological environments, represent future directions that may overcome current limitations. In conclusion, the convergence of MSC biology, biomaterial science, and advanced fabrication techniques holds great potential to revolutionize the treatment of bone and cartilage defects. Ongoing research and clinical validation are essential to realize the full therapeutic promise of these tissue engineering strategies