Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels

• Published in: Acta biomaterialia Vol. 8; no. 10; pp. 3754 - 3764
• Main Authors: Ma, Kun, Titan, Ashley L., Stafford, Melissa, Zheng, Chun hua, Levenston, Marc E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2012
• Subjects: Aggrecans - metabolism; Alginate; Alginates - pharmacology; Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; cartilage; Cattle; cell proliferation; Chondrogenesis; Chondrogenesis - drug effects; collagen; Collagen Type II - metabolism; DNA - metabolism; Elastic Modulus - drug effects; extensibility; Fibrin; Fibrin - pharmacology; fibrinogen; Fluorescent Antibody Technique; gels; gene expression; Gene Expression Regulation - drug effects; Glucuronic Acid - pharmacology; Glycosaminoglycans - metabolism; Hexuronic Acids - pharmacology; Humans; hydrocolloids; Hydrogel; Hydrogels - chemistry; mechanical properties; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Real-Time Polymerase Chain Reaction; Staining and Labeling; stem cells; Tensile Strength - drug effects; Thrombin - pharmacology; tissue engineering; Fibrin; Alginate; Hydrogel; Chondrogenesis; Mesenchymal stem cells
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2012.06.028

Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with each material offering distinct advantages and disadvantages. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40mgml−1 fibrinogen blended with 8mgml−1 alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition.