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.
Solution blow spinning (SBS) is a promising alternative to produce fibrous matrices for a wide range of applications, such as packaging and biomedical devices. Polycaprolactone (PCL) is a biodegradable polyester commonly used for spinning. The usual choices for producing PCL solutions include chlorinated solvents (CS), such as chloroform. However, the high toxicity of CS makes it difficult for biological and green applications. This work evaluates the influence of two less toxic solvents, acetic acid (AA) and acetone (Acet), and their mixtures (AA/Acet) on the properties of PCL fibers produced by SBS. The results showed that Acet does not cause degradation of the PCL chains, in opposition to AA. Furthermore, adding acetone to the acetic acid tended to preserve the size of PCL chains. It was not possible to produce fibers using PCL in 100% acetone. However, the AA/Acet mixture allowed the efficient production of PCL fibers. The proportion of Acet and AA in the mixture modulated the fiber morphology and orientation, making it possible to use this green solvent system according to the desired application.
This study aimed to assess the response of 3D printed PLA scaffolds biomimetically coated with apatite on human primary osteoblast 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, and characterized by physical-chemical, morphological, and mechanical properties. The in vitro biological response was assessed with human primary osteoblast (HOb) spheroids. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, covered by apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 (PLA-CaP+rhBMP-2) on critical-sized defects (8 mm) of rat calvaria. Increased cell adhesion and in vitro release of growth factors (PDGF, bFGF, VEGF) was observed for PLA-CaP scaffolds when pre-treated with FBS. PLA-CaP+BMP2 presented higher values of newly formed bone (NFB) than other groups at all experimental periods (p<0.05), attaining 44.85% of NFB after 6 months. These findings indicate that functionalization of PLA scaffolds with biomimetic apatite can improve its biological properties in the presence of complex biological media. Its association with BMP2 may enhance bone repair, suggesting this strategy as a promising candidate for bone tissue engineering.
Polymers such as the biocompatible polyhydroxybutyrate (PHB) and the polysaccharide chitosan (Chi), a pH-sensitive polymer, have been studied for drug delivery applications and scaffolds production. In this work, matrices of PHB and Chi were produced by compression molding (SPHB-Chi) and loaded with a broad-spectrum biocide chlorhexidine (CHX) (SPHB-Chi-CHX). The matrices were analyzed by scanning electron microscope (SEM). The SPHB-Chi capacity to absorb and deliver CHX was evaluated by UV-Vis. The antibacterial activity of the samples against S. aureus, P. aeruginosa and E. coli (most common pathogens that cause infection in several body sites) was evaluated using the disk-agar diffusion method. The CHX release results were fitted by the Power Law model. The results suggested that the morphology and the CHX delivery profile were directly related to the Chi amount in the samples and also showed that the SPHB-Chi-CHX is able to inhibit the microorganism proliferation, constituting it as a potential candidate for oral applications.
11 April 2019 in Journal of Applied Polymer Science