Surface hydrophilicity: a key factor in developing bone tissue engineering constructs
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Poly(L-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) meets many of the requirements of a scaffolding material for bone tissue engineering, such as adequate biocompatibility, degradability, and tunable properties. However, poly(LLA-co-CL) scaffolding tends to be hydrophobic and does not favor cellular attachment and differentiation. The overall purpose of this research project was to improve the physical and chemical properties of poly(LLA-co-CL) scaffolds to enhance biological responses. The modifying effects were evaluated and characterized in vitro and in vivo. The aim of Paper I was to compare the influence on bone regeneration of low (1 × 106 cells/scaffold) and high (2 × 106 cells/scaffold) seeding densities of bone marrow stromal stem cells (BMSCs) onto poly(LLA-co-CL) scaffolds. The influence of osteogenic supplements was also assessed. Scaffolds seeded at high cell density exhibited higher mRNA expressions of osteogenic markers than those with low seeding density. Osteogenic supplements significantly increased cell proliferation; more bone was formed in response to high seeding density with osteogenic medium. The results show that cell seeding density and osteogenic supplements may have a synergistic effect on the induction of new bone. After optimizing the culture conditions for BMSCs, the hydrophilicity of the surfaces of poly(LLA-co-CL) scaffolding was increased, either by blending with Tween 80 (Paper II), or coating with nanodiamond particles (nDPs) (Paper III). Compared with pristine scaffolds, the modified poly(LLA-co-CL) scaffolds exhibited reduced albumin adsorption and significantly increased the seeding efficiency of BMSCs. In Paper II, poly(LLA-co-CL)/3% Tween 80 scaffolds implanted subcutaneously in rats exhibited significantly increased mRNA expression of Runx2 and de novo bone formation. In Paper III, BMSCs-seeded into poly(LLA-co- CL)/nDPs scaffolds were implanted into rat calvarial defects and live imaging at 12 weeks disclosed significantly increased osteogenic metabolic activity. Microcomputed tomography, confirmed by histological data, revealed a substantial increase in bone volume. These results show that increasing the density of cell seeding onto poly(LLAco- Cl) scaffolds promotes BMSCs differentiation and bone formation. Modifying the surface of poly(LLA-co-CL) scaffolds to improve hydrophilicity promotes osteoconductivity and bone regeneration.
Består avPaper I: Mohammed Ahmed Yassin, Knut N. Leknes, Torbjørn Østvik Pedersen, Zhe Xing, Yang Sun, Stein Atle Lie, Anna Finne-Wistrand, Kamal Mustafa. Cell seeding density is a critical determinant for copolymer scaffolds-induced bone regeneration. Journal of Biomedical Materials Research Part A 2015;103(11):3649- 3658. The article is available at: http://hdl.handle.net/1956/10917
Paper II: Mohammed Ahmed Yassin, Knut N. Leknes, Yang Sun, Stein Atle Lie, Anna Finne- Wistrand, Kamal Mustafa. Surfactant tuning of hydrophilicity of porous degradable copolymer scaffolds promotes cellular proliferation and enhances bone formation. Journal of Biomedical Materials Research Part A 2016;104(8):2049- 2059. The article is available in the main thesis. The article is also available at: http://dx.doi.org/10.1002/jbm.a.35741
Paper III: Mohammed Ahmed Yassin, Kamal Mustafa, Zhe Xing, Yang Sun, Kristine Eldevik Fasmer, Thilo Waag, Anke Krueger, Doris Steinmüller-Nethl, Anna Finne-Wistrand, and Knut N. Leknes. Polymer scaffolds functionalized with nanodiamond particles enhances osteogenic metabolic activity and bone regeneration. Accepted in Macromolecular Bioscience. Full text not available in BORA.