Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 6; no. 27; pp. 4437 - 4445
• Main Authors: Czekanska, Ewa M, Geng, Jin, Glinka, Michael, White, Kate, Kanczler, Janos, Evans, Nicholas D, Oreffo, Richard O C, Bradley, Mark
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.07.2018
• Subjects: Angiogenesis; Ascorbic acid; Avidin; Biocompatibility; Biodegradability; Biodegradation; Biological activity; Biological effects; Biomaterials; Biomedical materials; Biotin; Bone healing; Cells (biology); Chorioallantoic membrane; Collagen; Combinatorial analysis; Conjugation; Encapsulation; Endothelial cells; Glycolic acid; Molecular chains; Nanoparticles; Polylactide-co-glycolide; Progenitor cells; Scaffolds; Stem cells; Streptavidin; Tissue engineering; Vascular endothelial growth factor
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c8tb00474a

The combination of supportive biomaterials and bioactive factors to stimulate endogenous progenitor cells is of key interest for the treatment of conditions in which intrinsic bone healing capacities are compromised. To address this need a "scaffold-decoration platform" was developed in which a biocompatible, biotin-functionalised 3D structural polymer network was generated through a solvent blending process, and used to recruit avidin modified nanoparticles within its 3D structure through biotin-avidin conjugation. This was enabled via the generation of a suite of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, encapsulating two bioactive factors, vascular endothelial growth factor (VEGF) and l-ascorbic acid 2-phosphate (AA2P) and conjugated to streptavidin to allow attachment to the bone generating scaffold. The levels of encapsulated and released VEGF and AA2P were tailored to fall within the desired range to promote biological activity as confirmed by an increase in endothelial cell tubule formation and collagen production by osteoblast cells in response to nanoparticle release of VEGF and AA2P, respectively. The release of VEGF from the scaffolds produced a significant effect on vasculature development within the chick chorioallantoic membrane (CAM) angiogenic assay. Similarly, the scaffolds showed strong biological effects in ex vivo assays indicating the potential of this platform for localised delivery of bioactive molecules with applications in both hard and soft tissue engineering.