ABSTRACT
This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods (p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity.
ABSTRACT
The majority of synthetic polymers used in 3 D printing are not designed to promote specific cellular interactions and hence possess limited bioactivity. Most of the strategies proposed to overcome this limitation demand multiple and expensive processing steps. This study aimed to evaluate the surface modification of 3D-printed poly(lactic acid) (PLA) scaffolds with polydopamine (PDA) coating as an alternative strategy to enhance their bioactivity and to facilitate the immobilization of type I collagen (COL I) onto the implant surface. Physical and chemical properties of PLA scaffolds coated with PDA, COL I or both were evaluated. The response of porcine bone marrow stem cells (MSCs) to the coatings was also investigated. The PDA layer improved COL immobilization onto the surface of the PLA scaffolds by 92%. The combination of PDA and COL functionalizations provided the best conditions for early-stage (<7 days) cell response. In addition, the PDA plus COL surface facilitated the robust deposition of extracellular matrix in the first 14 days of cell culture. Although the behavior of the MSCs appeared to be similar for both uncoated PLA and PDA plus COL-coated scaffolds by day 21, cells seeded onto PDA plus COL scaffolds produced substantially higher amounts of alkaline phosphatase. These results indicate that the osteoinductivity of 3D-printed PLA scaffolds can be enhanced by PDA and type I collagen coatings. This surface modification of polymeric scaffolds represents a promising strategy for bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 37-49, 2019.
