Calcium phosphate and bioglass reinforced PLA thin film biocomposites for slow drug delivery applications

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The rise in the number of musculoskeletal disorders (MSDs) due to the increase in aging population and advancement in medical technology has led to an increasing demand for medication to prevent and treat these diseases. The development of new drugs or formulations to allow treatment of these diseases in their very early stages is only increasing. Local direct and multidelivery of medication and key minerals to support bone repair and regeneration at the defect site, from flexible degradable devices at the rate within the therapeutic window, seems to be an effective strategy. However current drug delivery vehicles are neither flexible and degradable, nor able to deliver both medication and minerals effectively. Using a simple “solution casting” method, preparation of medical devices with such potential for slow drug delivery for biomedical applications served as the research objective. Polylactic acid (PLA) and hydroxyapatite-hydrothermally converted coral were used to develop PLA thin film composites as drug delivery systems. PLA provided flexibility and biodegradability of the systems, while coralline hydroxyapatite provided a unique architecture with its porous and bioactive nature, which is suitable for drug loading and slow drug release. Two drugs, gentamicin (antibiotic) and bisphosphonate were loaded into the device and their release profiles and activities were studied for the treatment of medical-implant related infection and osteoposis respectively. The biocompatibility study on human adipose derived stem cells (hADSC) and biofilm formation behaviour of both gram-negative (Pseudomonas aeruginosa) and gram-positive bacterial (Staphylococcus aureus) were studied on PLA thin film composites loaded with gentamicin. The mechanical properties of PLA-surface treated bioglass for tissue engineering applications was also studied. An alternative conversion method of coralline materials and other natural materials such as sea mussel and ostrich eggshells to calcium phosphate materials were also evaluated. Although nanosurface bioglass treated with 1% (3-Aminopropyl) triethoxysilane (APTES) suggested effective improvement in elongation at the break of PLA/bioglass composites, they lacked the required drug release efficiency. However, the PLA thin film composites displayed ability for potential applications in biomedical field as drug delivery systems. The flexibility they provide allows them to conform to any desired clinical shape and size. Incorporation of hydroxyapatite in the matrix, has the added advantages of controlled release, improved encapsulation efficiency, increased drug stability and maintenance of bioactivity and continuous supply of calcium Ca²⁺ and phosphate PO₄²⁻ ions, which can assist in bone regeneration and repair. Gentamicin release profiles, exhibited a steady state release rate, with significant antimicrobial activity even at high concentrations of bacteria. The systems also showed the potential for prolonged release of both antibiotic and bisphosphonate. The loading of the drug onto HAp particles induces a significant decrease of the release rate and period, for both gentamicin and bisphosphonate permitting the therapeutic efficacy of composite biomaterial locally to be extended. hADSC showed attachment and proliferation on PLA thin film-HAp composites signifying the increase in osteointegration due to the presence of HAp. Mechano-chemical conversion methods proved to be an effective alternative to the hydrothermal technique for coral conversion to calcium phosphate materials at moderate temperature conditions. The modified composites may have a wide range of biomedical applications in tissue engineering with improved elastic properties.
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