Porous 3D implants of degradable poly‐3‐hydroxybutyrate used to enhance regeneration of rat cranial defect

Abstract

The study describes preparation and testing of porous 3D implants of natural degradable polymer of 3-hydroxybutyric acid P(3HB) for regeneration of bone tissue defects. The ability of the P(3HB) implants to favor attachment and facilitate proliferation and directed differentiation of mesenchymal stem cells (MSCs) was studied in the culture of MSCs isolated from bone marrow and adipose tissue. Tissue-engineered hybrid systems (grafts) constructed using P(3HB) and P(3HB) in combination with osteoblasts were used in experiments on laboratory animals (n = 48) with bone defect model. The defect model (5 mm in diameter) was created in the rat parietal bone, and filling of the defect by the new bone tissue was monitored in the groups of animals with P(3HB) implants, with commercial material, and without implants (negative control). Computed tomography (CT) and histologic examination showed that after 120 days, in the group with the osteoblast-seeded P(3HB) implants, the defect was completely closed; in the group with the cell-free P(3HB) implants, the remaining defect was no more than 10% of the initial one (0.5 mm); in both the negative and positive controls, the size of the defect was about 1.0-1.2 mm. These results suggest that P(3HB) has good potential as osteoplastic material for reconstructive osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 566-577, 2017.

Polyhydroxyalkanoates (PHA) for therapeutic applications

“…The ability of porous 3D implants P(3HB) to favor attachment and facilitate proliferation and directed differentiation of mesenchymal stem cells (MSCs) was studied in the culture of MSCs isolated from bone marrow and adipose tissue. And results suggest that P(3HB) has good potential as osteoplastic material for reconstructive osteogenesis [25].…”

Application of Polyhydroxyalkanoates in Medicine and the Biological Activity of Natural Poly(3-Hydroxybutyrate)

“…A thin fibrous capsule (~ 100 μm) is formed during a month and is resorbed once the samples have biodegraded [19–22]. Many studies revealed a low lymphocyte count or virtually no lymphocytes (in particular, T lymphocytes) at the PHB insertion site, indicating that the immune reaction to this polymeric biomaterial is either significantly reduced or absent [23–26]. It was demonstrated that deeply purified PHB and PHBV also exhibit good hemocompatibility, so they can be used to produce blood-contacting medical devices: patches for the pericardial wall, the pulmonary artery, and the right atrium, as well as biodegradable coronary stents [25–30].…”

“…Implantation of the PHB-based porous scaffold leads to vigorous vascularization of the scaffold and emergence of islets of the bone tissue newly formed from the granulation tissue in its pores [23, 24, 31]. Evaluation of the expression levels of various cytokines and other markers of inflammation in the implantation site of medical devices based on PHB (and its copolymer PHBV) revealed reduced expression levels of proinflammatory cytokines (interleukins, tumor necrosis factor, monocyte chemoattractant protein, inducible nitric oxide synthase, and C-reactive protein) compared to those for other materials and increased expression of genes encoding various proteins (type I collagen, caveolin-1, cytokeratin, heparan sulfate proteoglycan, thrombomodulin, and prostacycline), which are markers of regenerative processes taking place in cardiac, vascular, intestinal, neural, and osseous tissues [23, 25, 27, 28, 32–35]. However, chronic inflammatory response to the implantation of PHB-based devices (e.g., coronary stent prototypes) was observed in some cases.…”

Effect of Hydrogen Dioxide Treatment on the Osteogenic Potential of Duck-beak Bone-derived Natural Bioceramic Microparticles

“…Powerful osteogenic potential of autogenous bone makes this graft be regarded as the "gold standard"; however, this graft has disadvantage in limited quantity and donor morbidity (1). It is, thus, required to find three-dimensional (3D), biodegradable and biocompatible scaffolds mimicking the bone tissue architecture for tissue engineering applications as an alternative (2,3). Although soft scaffolds (e.g., hydrogels or collagen sponge) have been predominantly used in the tissue engineering filed, these are limited by their poor mechanical properties.…”