Characterization of a dual function minocycline-loaded bone scaffold

• Autor(a) principal: Anjos, Inês Isabel Lopes dos
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/85986
• topic: Bone-infection; scaffold; local-drug-delivery; minocycline; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

It is estimated that orthopedic procedures will rise due to population growth along with aging and increasing on chronic diseases. Consequently, orthopedic infections associated to these procedures can be a serious complication, leading to a state of morbidity. Current strategies for treating bone infections and defects present several limitations, namely low local concentrations and systemic toxicity. To overcome these problems, synthetic and biocompatible bone grafts (scaffolds) are being developed as platforms for local drug delivery, a strategy that allows high antibiotics’ concentration in bone and low systemic toxicity. The present work aims to develop a novel drug delivery system with osteoconductive and osteoinductive properties for bone regeneration and capable of treating the infection. For this purpose, porous poly (DL-lactide acid) scaffolds were produced by solvent casting technique, functionalized with bioglass (BG) and collagen (Col) and loaded with 0.5, 0.25, 0.1, 0.05 or 0.005 mg/mL of minocycline hydrochloride (MH), a dual function drug that beyond its antibiotic role, also induces osteoblastic cells differentiation. Scaffolds’ surface morphology was characterized by scanning electron microscopy (SEM) and elemental chemical composition was performed by X-ray energy dispersive spectrometer (EDS). Interactions between drug and polymer were studied by differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). These drug delivery systems were also characterized in terms of drug release profiles, cytocompatibility, through in vitro studies, and finally microbiological studies were performed to access antimicrobial activity and biofilm inhibition capacity of these scaffolds. SEM analysis and EDS results demonstrated a porous surface and confirmed the scaffolds’ functionalization. Regarding drug release profiles, the obtained results suggest a two-phase stage release, with an initial burst release in the first 15 minutes of the assay, followed by a sustained release. In vitro cell studies were promising for scaffolds adsorbed with 0.1 and 0.05 mg/mL of MH, not revealing cytotoxicity, contrary to what was seen for scaffolds with higher concentrations of MH (0.5 and 0.25 mg/mL). Finally, microbiological assays showed antimicrobial activity and inhibition of biofilm production by Staphylococcus aureus for all the groups of antibiotic adsorbed scaffolds. In conclusion, these scaffolds proved to be bioactive, supporting matrix mineralization which is inherent to bone formation, and to have anti-microbial and anti-biofilm effect, being a promising strategy for an acute infection treatment or to prevent the risk of infection in the first hours after surgery or even to mediate bone regeneration.