Collagen and bone morphogenetic protein-2 functionalized hydroxyapatite scaffolds induce osteogenic differentiation in human adipose-derived stem cells.

Surface modification is one important way to fabricate successful biocompatible materials in bone tissue engineering. Hydroxyapatite (HAp) materials have received considerable attention as suitable bioceramics for manufacturing osseous implants because of their similarity to bone mineral in terms of chemical composition. In this study, the surface of porous HAp scaffold was modified by collagen treatment and bone morphogenetic protein-2 (BMP-2) conjugation. The surface modification did not affect the HAp scaffold's bulk properties. No significant difference in compressive strength was found among different scaffolds, with HAp, collagen modified HAp, and collagen-BMP-2-functionalized HAp having compressive strengths of 45.8 ± 3.12, 51.2 ± 4.09, and 50.7 ± 3.98 MPa, respectively. In vitro studies were performed to compare adhesion and osteogenic differentiation between human adipose-derived stem cells (hADSCs) with modified surfaces and those unmodified HAp surfaces. Collagen or BMP-2 alone was insufficient and that both collagen and BMP-2 are necessary to get the desired results. The findings suggest the possibility of using three-dimensional HAp scaffold treated with gold-standard collagen coating and highly researched BMP-2 growth factor as a platform to deliver hADSCs. Results of this study could be used to develop treatment strategy for regenerating completely transected models using more synergistic approaches.

Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP porous spongy scaffold as a controlled drug delivery system for bone tissue regeneration.

The main objective of this study was to fabricate a controlled drug delivery which is simultaneously effective for bone regeneration. We have encapsulated simvastatin, which enhances osteoblastic activity, in the poly (lactic-co-glycolic acid) microspheres. Loading of these microspheres inside the spongy scaffold of biphasic calcium phosphate with the help of Gelatin (Gel) hydrogel controls the delivery of the drug, and ensures a more favorable drug release profile. As a result, some significant benefits have been achieved, such as higher mechanical strength, excellent biocompatibility in in vitro experiments. For determining the characteristics of the composite scaffold, several analysis, such as scanning electron microscope, EDX, X-ray diffraction, FT-IR, and porosity were carried out. The in vitro drug release profile clearly indicates that simvastatin release from the microsphere was more controlled and prolonged after loading in the scaffold. Biocompatibility was certainly higher for the final composite scaffold compared to drug unloaded scaffold, as assessed through MTT assay and Confocal imaging with MC3T3-E1 pre-osteoblast cells. Cell attachment and proliferation were certainly higher in the presence of drug loaded microspheres. Bone remodeling gene and protein expression were observed by real-time polymerase chain reaction and Western blot respectively. Simvastatin loaded scaffold exhibited the best results in every determination which was carried out.

Surface modification of porous polycaprolactone/biphasic calcium phosphate scaffolds for bone regeneration in rat calvaria defect.

In this study, polycaprolactone scaffolds fabricated by a salt-leaching process were loaded with biphasic calcium phosphate successfully to improve the osteoconductivity in bone regeneration. The surface of polycaprolactone/biphasic calcium phosphate scaffolds was aminolyzed by 1,6-hexamethylenediamine to introduce amino groups onto the surface, which was verified qualitatively by ninhyrin staining. Collagen was further immobilized on the aminolyzed porous polycaprolactone via N-ethyl-N'-(3-dimethylaminopropy) carbodiimide hydrochloride/hydroxy-2,5-dioxopyrolidine-3-sulfonic acid sodium cross-linking. The pore size of polycaprolactone/biphasic calcium phosphate-collagen scaffolds was 200-300 µm, which was suitable for bone in-growth. The X-ray photoelectron spectroscopy confirmed the coupling of collagen immobilized on the surface of polycaprolactone/biphasic calcium phosphate. In vitro results demonstrated that the spreading and viability of MC3T3-E1 cells were remarkably improved in the polycaprolactone/biphasic calcium phosphate-collagen scaffolds. The in vivo study was carried out by implanting the porous polycaprolactone, polycaprolactone/biphasic calcium phosphate, and polycaprolactone/biphasic calcium phosphate-collagen to the skulls of rats. Although the addition of biphasic calcium phosphate particles in the polycaprolactone scaffolds does not have a strong effect on the new bone formation, the immobilization of collagen on the polycaprolactone/biphasic calcium phosphate scaffolds significantly improved the bone regeneration even though the implantation time was short, 6 weeks. The present results provide more evidence that functionalizing polycaprolactone with biphasic calcium phosphate and collagen may be a feasible way to improve the osteoconduction in bone regeneration.