RESUMO
Preventing bacterial colonization on scaffolds while supporting tissue formation is highly desirable in tissue engineering as bacterial infection remains a clinically significant risk to any implanted biomaterials. Elemental selenium (Se0) nanoparticles have emerged as a promising antimicrobial biomaterial without tissue cell toxicity, yet it remains unknown if their biological properties are from soluble Se ions or from direct cell-nanoparticle interactions. To answer this question, in this study, we developed a layered coating consisting of a Se nanoparticle layer underneath a micrometer-thick, biomimetic calcium phosphate (CaP) layer. We showed, for the first time, that the release of soluble HSe- ions from the Se nanoparticles strongly inhibited planktonic growth and biofilm formation of key bacteria, Staphylococcus aureus. The Se-CaP coating was found to support higher bone formation than the CaP-only coating in critical-size calvarial defects in rats; this finding could be directly attributed to the released soluble Se ions as the CaP layers in both groups had no detectable differences in the porous morphology, chemistry, and release of Ca or P. The Se-CaP coating was highly versatile and applicable to various surface chemistries as it formed through simple precipitation from aqueous solutions at room temperature and therefore could be promising in bone regeneration scaffolds or orthopedic implant applications.
Assuntos
Anti-Infecciosos/química , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis/farmacologia , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Selênio/química , Animais , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/patologia , Regeneração Óssea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/uso terapêutico , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Poliésteres/química , Impressão Tridimensional , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the site of dental implant placement. In this proof of concept study, we investigated the potential of a biphasic polycaprolactone construct combined with a hyaluronic acid based hydrogel loaded with recombinant human bone morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The biphasic scaffold consisted of an outer shell manufactured by fused deposition modelling, mimicking native cortical bone and providing mechanical and space maintenance properties essential for bone formation. Within this shell, a 90% porous melt electrospun microfibrous mesh mimicking the architecture of cancellous bone was incorporated in order to facilitate hydrogel loading and subsequent osteogenesis and angiogenesis. The in vitro performances of the biphasic construct demonstrated that BMP-2 was released in a sustained manner over several weeks and that cell viability was maintained in the hydrogel over 21â¯days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin, osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2. In vivo assessment of the biphasic scaffold was performed using a dose of 30⯵g of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology and micro-CT analysis of the elevated space demonstrated that the hydrogel and the presence of BMP-2 enabled bone formation. However, this was limited to the immediate vicinity of the calvarial bone. The amount of newly formed bone was relatively small which was likely due to poor vascularisation of the extraskeletal space. The utilisation of this biomimetic biphasic construct with excellent space maintenance properties can be of interest in dentistry although the in vivo model requires refinement to demonstrated appropriate efficacy.