Bioactive Sr(II)/Chitosan/Poly(ε-caprolactone) Scaffolds for Craniofacial Tissue Regeneration. In Vitro and In Vivo Behavior

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.

Chitosan Imparts Better Biological Properties for Poly(ε-caprolactone) Electrospun Membranes than Dexamethasone

“…22 In this facet, poly(ε-caprolactone)-chitosan-hydroxyapatite composite membrane scaffolds promoted proliferation and osteogenic differentiation of human dental pulp stem cells. 23 Poly(ε-caprolactone)-chitosan-based composite membranes have been used for wound healing, 24,25 wound dressing, 25 skin repair in burn wounds, 26 cranial tissue regeneration, 27 bladder regeneration, 20 cartilage defect repair, 28 and other applications. Vacanti et al 29 produced poly(ε-caprolactone) and poly(L-lactic)-poly(ε-caprolactone) nanofibers loaded with dexamethasone (5.7 wt.% of dexamethasone relative to dexamethasone and polymer content).…”

Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction

“…Tissue engineering has been found to address some of these limitations through development of biomimicking 3D matrices [4]. The repair of complex craniofacial bone defects is challenging and the success mainly depends on the choice of reconstructive method [24]. In order to design, develop, recreate and reconstruct a tissue defect, bioimplants (cell-based or cell-free) have emerged as a promising tool.…”

“…It is extracted from crustacean shells and marine sponges. It exhibits fungicidal and anti-microbial activities [24,41]. Its biodegradability, biocompatibility and excellent cell adhesive properties make it a popular choice for implant material [41].…”

The Applications of 3D Printing for Craniofacial Tissue Engineering

“…As PCL is bioinert, other biological active components such as TCP, HA, decellularized trabecular bone, or growth factors were incorporated into the 3D printing system [21,79,80]. Furthermore, the acidic environment caused by the degradation products of PCL and its hydrophobic nature can be somewhat diminished by the inclusion of hydrophilic polymers like PEG and the surface coating of natural polymers like chitosan [81,82]. PCL scaffolds are well-suited for extrusion-based 3D-printing (Figure 4A), FDM for example, due to the relatively low melting points (62 °C).…”