Abstract
In craniofacial tissue regeneration, the current gold standard treatment is autologous bone grafting, however, it presents some disadvantages. Although new alternatives have emerged there is still an urgent demand of biodegradable scaffolds to act as extracellular matrix in the regeneration process. A potentially useful element in bone regeneration is strontium. It is known to promote stimulation of osteoblasts while inhibiting osteoclasts resorption, leading to neoformed bone. The present paper reports the preparation and characterization of strontium (Sr) containing hybrid scaffolds formed by a matrix of ionically cross-linked chitosan and microparticles of poly(ε-caprolactone) (PCL). These scaffolds of relatively facile fabrication were seeded with osteoblast-like cells (MG-63) and human bone marrow mesenchymal stem cells (hBMSCs) for application in craniofacial tissue regeneration. Membrane scaffolds were prepared using chitosan:PCL ratios of 1:2 and 1:1 and 5 wt % Sr salts. Characterization was performed addressing physico-chemical properties, swelling behavior, in vitro biological performance and in vivo biocompatibility. Overall, the composition, microstructure and swelling degree (≈245%) of scaffolds combine with the adequate dimensional stability, lack of toxicity, osteogenic activity in MG-63 cells and hBMSCs, along with the in vivo biocompatibility in rats allow considering this system as a promising biomaterial for the treatment of craniofacial tissue regeneration.
Highlights
Reconstruction of large bone defects still continue as a major challenge for orthopedists, and craniomaxillofacial surgeons
Composite membranes formed by chitosan/alginate polymers and octacalcium phosphate/bioactive glasses were suitable for adhesion and growth of human bone marrow mesenchymal stem cells [67]
Content normalized for DNA was significantly higher compared to the blank in MG-63 cell culture at 14 days and in human bone marrow mesenchymal stem cells (hBMSCs) culture at 7 and 14 days. These results show the osteogenic capacity of the hybrid membranes that can be tentatively attributed to the presence of Sr(II) ions, according to Seol et al, chitosan sponges can enhance alkaline phosphatase (ALP) [51]
Summary
Reconstruction of large bone defects still continue as a major challenge for orthopedists, and craniomaxillofacial surgeons. The scaffolds usually loaded with osteoconductive/osteoinductive components and stem cells [5,6] are intrinsically biocompatible and some of them have reached clinical use with minimal adverse immunological reports [5] Osteoinductive components such as bioactive glasses [7,8], phosphate-based glasses [9] or hydroxyapatite (HAp) [10] have been investigated. The use of chitosan in orthopedic/periodontal applications [46,49,56] and craniofacial bone defects repair [37,57] has increased over the years as well as the development of hybrid systems [58,59,60,61]. Composite membranes formed by chitosan/alginate polymers and octacalcium phosphate/bioactive glasses were suitable for adhesion and growth of human bone marrow mesenchymal stem cells (hBMSCs) [67]. In vivo biocompatibility experiments are carried out applying a subcutaneous pocket rat model
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