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A latent TGF-β conjugated scaffold improves neocartilage development
Tianbai Wang1, Yifan Peng2, Bor-Lin Huang2
1Division of Materials Science & Engineering, Boston University, Boston, MA, USA.
Acta Biomaterialia
|November 22, 2025
Summary
Bio-inspired scaffolds delivering latent transforming growth factor-beta (LTGF-β) promote controlled neocartilage development. This approach improves cartilage composition and mechanical properties, mimicking native tissue and avoiding adverse effects of high TGF-β doses.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Conventional transforming growth factor-beta (TGF-β) supplementation for neocartilage development uses supraphysiologic doses, leading to undesirable cartilage features like hyperplasia and heterogeneities.
- Native cartilage regulates TGF-β through latent complexes (LTGF-β) activated by cells, ensuring moderated, physiologic dosing.
- Current methods struggle to replicate the controlled, localized delivery of TGF-β found in natural cartilage regeneration.
Purpose of the Study:
- To develop and evaluate a bio-inspired strategy using LTGF-β-conjugated scaffolds for controlled TGF-β delivery in neocartilage engineering.
- To compare the efficacy of LTGF-β scaffolds against conventional active TGF-β media supplementation (MS) at various doses.
- To assess the impact of LTGF-β scaffolds on neocartilage composition, structure, mechanical properties, and cell phenotype.
Main Methods:
- LTGF-β-conjugated scaffolds were created and seeded with bovine chondrocytes within agarose constructs.
- Constructs were compared to those supplemented with active TGF-β at physiologic (0.3 ng/mL) and supraphysiologic (10 ng/mL) doses, or no TGF-β.
- Evaluations included mechanical properties, sGAG content, cell morphology, collagen distribution, gene expression (COL-I, COL-X), and tissue heterogeneity.
Main Results:
- LTGF-β scaffolds achieved native-matched mechanical properties and sGAG content, with cell morphology and collagen distribution resembling hyaline cartilage.
- These scaffolds significantly reduced COL-I and COL-X expression compared to TGF-β-free and MS-10 groups, indicating an optimal chondrogenic phenotype.
- LTGF-β scaffolds minimized mechanical and biochemical heterogeneities, outperforming both MS-0.3 and MS-10 groups.
Conclusions:
- LTGF-β-conjugated scaffolds provide a bio-inspired platform for localized, cell-mediated TGF-β activation at physiologic levels.
- This approach successfully improves neocartilage composition, structure, material properties, and cell phenotype, mitigating issues of conventional TGF-β delivery.
- The LTGF-β scaffold strategy offers a promising solution for enhanced cartilage regeneration outcomes.
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