This review focuses on a somewhat unexplored strand of regenerative medicine, that is in situ tissue engineering. In this approach manufactured scaffolds are implanted in the injured region for regeneration within the patient. The scaffold is designed to attract cells to the required volume of regeneration to subsequently proliferate, differentiate, and as a consequence develop tissue within the scaffold which in time will degrade leaving just the regenerated tissue. This review highlights the wealth of information available from studies of ex-situ tissue engineering about the selection of materials for scaffolds. It is clear that there are great opportunities for the use of additive manufacturing to prepare complex personalized scaffolds and we speculate that by building on this knowledge and technology, the development of in situ tissue engineering could rapidly increase. Ex-situ tissue engineering is handicapped by the need to develop the tissue in a bioreactor where the conditions, however optimized, may not be optimum for accelerated growth and maintenance of the cell function. We identify that in both methodologies the prospect of tissue regeneration has created much promise but delivered little outside the scope of laboratory-based experiments. We propose that the design of the scaffolds and the materials selected remain at the heart of developments in this field and there is a clear need for predictive modelling which can be used in the design and optimization of materials and scaffolds.

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Biofabrication allows the formation of 3D scaffolds through a precise spatial control. This is of foremost importance when aiming to mimic heterogeneous and anisotropic architecture, such as that of the osteochondral tissue. Osteochondral defects are a supreme challenge for tissue engineering due to the compositional and structural complexity of stratified architecture and contrasting biomechanical properties of the cartilage-bone interface. This review highlights the advancements and retreats witnessed by using developed bioinks for tissue regeneration, taking osteochondral tissue as a challenging example. Methods, materials and requirements for bioprinting were discussed, highlighting the pre and post-processing factors that researchers should consider towards the development of a clinical treatment.

Self-curing acrylic bone cements are widely used in the fixation of prosthetic implants in orthopaedic surgery. Commercial bone cements are rendered radiopaque by the addition of heavy metal salts of barium and zirconia. The addition of barium sulphate adversely affects the mechanical strength and fracture toughness of bone cement and despite the fact that it has low solubility in water; its slow release and subsequent toxicity have caused concern. In an earlier study triphenyl bismuth (TPB) was found to be a viable alternative as a radiopaque agent in acrylic bone cements, which provided enhanced homogeneity. In this study we report the effect of the inclusion of TPB on the thermal properties of PMMA-based bone cements using both conventional DSC and Modulated Temperature DSC. Furthermore, analysis of the residual monomer contents is reported analysed by NMR spectroscopy in order to ascertain the influence of TPB on the polymerisation reaction. The glass transition temperature (Tg) determined by DSC showed that the values decreased with the addition of increasing amounts of TPB through both blending and dissolution methods; however, the method of incorporating TPB did not influence Tg. The magnitude of reduction was dependent of the amount of TPB and was greatest in the case of highest concentration of TPB used. A TPB melting peak was observed in the 25 wt% TPBBC, suggesting a limit to the solubility of TPB. The residual monomer analysis showed that at 10 and 15% by weight of TPB in the cement caused no significant changes in the residual monomer content but 25 wt% of TPB exhibited a significantly higher residual monomer content.

IntroductionIn this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by chronic inflammation is associated with an imbalance in bone turnover and also a disorganization of the bone type I collagen network.MethodsSerum, vertebrae and femur bones were collected from eight-month-old polyarthritis SKG mice and controls. Strength of the femoral bones was evaluated using three-point bending tests and density was assessed with a pycnometer. Bone turnover markers carboxy-terminal collagen cross-linking telopeptides (CTX-I) and amino-terminal propeptide of type I procollagen (PINP) were measured in serum. The organization and density of bone collagen were analyzed in vertebrae using second-harmonic generation (SHG) imaging with a two-photon microscope and trabecular bone microstructure was assessed by scanning electron microscope (SEM).ResultsFemoral bones of SKG mice revealed increased fragility expressed by deterioration of mechanical properties, namely altered stiffness (P = 0.007) and reduced strength (P = 0.006), when compared to controls. Accordingly, inter-trabecular distance and trabecular thickness as observed by SEM were reduced in SKG mice. PINP was significantly higher in arthritic mice (9.18 ± 3.21 ng/ml) when compared to controls (1.71 ± 0.53 ng/ml, P < 0.001). Bone resorption marker CTX-I was 9.67 ± 3.18 ng/ml in arthritic SKG mice compared to 6.23 ± 4.11 ng/ml in controls (P = 0.176). The forward-to-backward signal ratio measured by SHG was higher in SKG animals, reflecting disorganized matrix and loose collagen structure, compared to controls.ConclusionsWe have shown for the first time that chronic arthritis by itself impairs bone matrix architecture, probably due to disturbed bone remodeling and increased collagen turnover. This effect might predispose patients to bone fragility fractures.

Radiopaque cement containing barium sulfate causes significantly more bone resorption in vivo and in vitro than radiolucent cement. The aim of this study was to investigate the osteolytic potential of an alternative radiopaque agent, triphenyl bismuth (TPB). Bone cement particles containing various concentration of TPB (15 and 25 wt %) prepared by two methods, blending and dissolution, were added to monocytes in a bone resorption assay and the extent of lacunar resorption on dentine slices was determined. The results clearly show that cement particles containing TPB cause less bone resorption than cement particles containing barium sulfate. In addition, our results suggest that TPB prepared by dissolution in bone cement induces less osteolytic response than TPB-cement prepared by blending. The osteolysis in response to bone cement wear particles may therefore be reduced with TPB prepared using the blending technique.

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