Bone cements are extensively employed in orthopaedics for joint arthroplasty, however implant failure in the form of aseptic loosening is known to occur after long-term use. The exact mechanism causing this is not well understood, however it is thought to arise from a combination of fatigue and chemical degradation resulting from the hostile in vivo environment. In this study, two commercial bone cements were aged in an isotonic fluid at physiological temperatures and changes in moisture uptake, microstructure and mechanical and fatigue properties were studied. Initial penetration of water into the cement followed Fickian diffusion and was thought to be caused by vacancies created by leaching monomer. An increase in weight of approximately 2% was experienced after 30 days ageing and was accompanied by hydrolysis of poly(methyl methacrylate) (PMMA) in the outermost layers of the cement. This molecular change and the plasticising effect of water resulted in reduced mechanical and fatigue properties over time. Cement ageing is therefore thought to be a key contributor in the long-term failure of cemented joint replacements. The results from this study have highlighted the need to develop cements capable of withstanding long-term degradation and for more accurate test methods, which fully account for physiological ageing.
10 August 2015 in Journal of Biomedical Materials Research Part B: Applied Biomaterials
Progress made by materials scientists in recent years has greatly helped the field of ultra-precision manufacturing. Ranging from healthcare to electronics components, phenomena such as twinning, dislocation nucleation, and high-pressure phase transformation have helped to exploit plasticity across a wide range of metallic and semiconductor materials. One current problem at the forefront of the healthcare sector that can benefit from these advances is that of bacterial infections in implanted prosthetic devices. The treatment of implant infections is often complicated by the growth of bacterial biofilms on implant surfaces, which form a barrier that effectively protects the infecting organisms from host immune defenses and exogenous antibiotics. Further surgery is usually required to disrupt the biofilm, or to remove the implant altogether to permit antibiotics to clear the infection, incurring considerable cost and healthcare burdens. In this review, we focus on elucidating aspects of bactericidal surfaces inspired by the biological world to inform the design of implant surface treatments that will suppress bacterial colonization. Alongside manufacturing and materials related challenges, the review identifies the most promising natural bactericidal surfaces and provides representative models of their structure, highlighting the importance of the critical slope presented by these surfaces. The scalable production of these complex hierarchical structures on freeform metallic implant surfaces has remained a scientific challenge to date and, as identified by this review, is one of the many 21st-century puzzles to be addressed by the field of applied physics.
Bioactive growth factors identified within the extracellular matrix of dentine have been proposed roles in regulating the naturally inherent regenerative dentine formation seen in teeth in response to trauma and infection, which may also be harnessed for novel clinical treatments in augmenting mineralised tissue repair. This study examined the specific biological action of demineralised dentine matrix extract on a clonal population of dental pulp stem cells in stimulating the prerequisite stages of wound healing associated with mineralised tissue repair. A clonal dental pulp stem cell population with sustained proliferative capacity and multi-potentiality towards osteogenic, adipogenic and chondrogenic lineages was isolated from the pulp of human third molars. Dentine was collected from human healthy teeth, powdered and treated with ethylenediaminetetraacetic acid to obtain a solubilised DDM protein extract. The influence of DDM on the DPSC clonal population was assessed in vitro. Exposure of cells to proteolytically degraded DDM or unsupplemented media served as controls. Compared to controls, DDM stimulated cell expansion, reduced apoptotic marker caspase 3, increased cell survival marker Akt1 and enhanced mineralised matrix deposition as determined by mineral deposition and increased expression of bone-related markers, alkaline phosphatase and osteopontin. Dental pulp stem cells successfully migrated into collagen gels supplemented with demineralised dentine matrix, with cells remaining viable and expanding in numbers over a 3-day period. Collectively, the results provide evidence that soluble proteins extracted from dentine matrix are able to exert a direct biological effect on dental pulp stem cells in promoting mineralised tissue repair mechanisms.
Current dental restorations have short longevity, and consequently, there is a need for novel tissue engineering strategies that aim to regenerate the dentin-pulp complex. Dentin matrix contains a myriad of bioactive growth factors and extracellular matrix proteins associated with the recruitment, proliferation, and differentiation of dental pulp progenitor cells. In this study, we show that demineralized dentin matrix (DDM), from noncarious dentine, can be encapsulated into liposomes for delivery to dental tissue to promote regeneration. Liposomes were formulated to encapsulate 0–100 μg/mL DDM, lysed with Triton X, and used in vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) enzyme-linked immunosorbent assays to quantify release. The encapsulation efficiencies were calculated to be 25.9% and 28.8% (VEGF/TGF-β1) for 50 μg/mL DDM liposomes and 39% and 146.7% (VEGF/TGF-β1) for 100 μg/mL DDM liposomes. All liposome formulations had no cytotoxic effects on a dental pulp stem cell (DPSC) clone, as shown by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide), Caspase 3/7 assays, and cell counts. The ability of the liposomes to stimulate DPSC chemotactic recruitment was tested by Boyden chamber chemotaxis assays. Unloaded liposomes alone stimulated significant progenitor cell recruitment, while DDM-loaded liposomes further promoted chemotactic recruitment in a dose-dependent manner. DDM liposomes promoted the upregulation of “osteodentin” markers osteocalcin and RUNX2 (Runt-related transcription factor 2) in DPSCs after 9 days of treatment, determined by real-time quantitative PCR. Furthermore, Alizarin Red S staining showed that unloaded liposomes alone induced biomineralization of DPSCs, and DDM liposomes further increased the amount of mineralization observed. DDM liposomes were more effective than free DDM (10 μg/mL) at activating recruitment and osteogenic differentiation of DPSC, which are key events in the endogenous repair of the dentin-pulp complex. The study has highlighted the therapeutic potential of bioactive DDM liposomes in activating dental tissue repair in vitro , suggesting that liposomal delivery from biomaterials could be a valuable tool for reparative dentistry and hard-tissue engineering applications.