Ectopic bone formation by gel-derived bioactive glass-poly-L-lactide-co-glycolide composites in a rabbit muscle model

Abstract

In this study we aimed to assess the in vivo osteoinductive properties of two composite scaffolds made of PLGA (poly-L-lactide-co-glycolide) and two types of gel-derived bioactive glasses, namely a high silica S2 bioactive glass (S2-PLGA composites) or high lime A2 bioactive glass (A2-PLGA composites). To achieve that, the potential of the composites to induce ectopic bone formation in a rabbit muscle has been examined along with the control PLGA scaffold. Cylinder-like scaffolds of 7 × 3 mm (width × height) were implanted into pouches created in the latissimus dorsi muscle of 18 New Zealand rabbits. The tissue sections were obtained at 6, 12 or 24 weeks post-surgery (six rabbits per each time point) and stained with hematoxylin-eosin. The process of wound healing, the formation of collagen-rich connective tissue and its transition to cartilage were examined by Sirius red and Alcian blue histological stainings. We also performed immunohistochemical verification of the presence of osteoblast- and osteoclast- like cells in the vicinity of the scaffolds. A typical foreign body reaction and wound healing process was observed for all implanted scaffolds. Osteoblast- and osteoclast-like cells were observed in the vicinity of the scaffolds as determined by the immunohistochemical staining for Osteocalcin, BMP-2 and Cathepsin K. Compared to plain PLGA scaffolds, numerous osteoblast-like cells were observed 12 weeks post implantation near the composites and the scaffolds gradually degraded as bone formation proceeded. S2-PLGA and A2-PLGA composites display osteoinductive properties in vivo. Furthermore, they are more effective at inducing ectopic bone formation in a rabbit muscle compared to plain PLGA. Thus these SBG-PLGA composite scaffolds have potential for clinical applications in dental and/or orthopedic-bone tissue engineering.

Molecular Indicators of Biomaterials Osteoinductivity - Cell Migration, BMP Production and Signalling Turns a Key

“…Verification of selected scaffolds was done in a rabbit model, basically as previously described [27]. This study was approved by the local Ethical Committee of the Jagiellonian University, decision no.…”

In Vivo Behavior of Bioactive Glass-Based Hybrids in Animal Models For Bone Regeneration

“…Compared to PLGA alone, the composite scaffolds gradually degraded as bone formation took place and were more effective at inducing ectopic bone formation. The presence of osteoblast-like and osteoclast-like cells was noted in the vicinity of the scaffolds, confirmed by immunohistochemical staining for osteocalcin, bone morphogenetic protein-2 (BMP-2), and cathepsin K [48]. compared to uncoated S53P4 (Figure 3) [49].…”

Molecular Indicators of Biomaterials Osteoinductivity - Cell Migration, BMP Production and Signalling Turns a Key

“…Examining early osteogenic transcription factors showed that the expression levels of Runx-2 and Osx were generally higher for cells cultured on the scaffolds without P Ectopic bone formation is a standard procedure to verify osteoinductivity of materials [30]. Previously, we examined osteoinductive potential of selected scaffolds of SiO 2 -CaO-P 2 O 5 system, namely A2/PLGA and S2/PLGA composites, and both scaffolds were more effective at inducing ectopic bone formation in a rabbit muscle compared to plain PLGA [27]. Giving that our in present in vitro studies the scaffolds depleted of P 2 O 5 , i.e.…”

“…Veri cation of selected scaffolds was done in a rabbit model, basically as previously described [27]. This study was approved by the local Ethical Committee of the Jagiellonian University, decision no.…”