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Calcium phosphate cements (CPCs) are clinically effective void fillers that are capable of bridging calcified tissue defects and facilitating regeneration. However, CPCs are completely synthetic/inorganic, unlike the calcium phosphate that is found in calcified tissues, and they lack an architectural organization, controlled assembly mechanisms, and have moderate biomechanical strength, which limits their clinical effectiveness. Herein, we describe a new class of bioinspired CPCs that can glue tissues together and bond tissues to metallic and polymeric biomaterials. Surprisingly, alpha tricalcium phosphate cements that are modified with simple phosphorylated amino acid monomers of phosphoserine (PM-CPCs) bond tissues up to 40-fold stronger (2.5–4 MPa) than commercial cyanoacrylates (0.1 MPa), and 100-fold stronger than surgical fibrin glue (0.04 MPa), when cured in wet-field conditions. In addition to adhesion, phosphoserine creates other novel properties in bioceramics, including a nanoscale organic/inorganic composite microstructure, and templating of nanoscale amorphous calcium phosphate nucleation. PM-CPCs are made of the biocompatible precursors calcium, phosphate, and amino acid, and these represent the first amorphous nano-ceramic composites that are stable in liquids.

The purpose of this study was to evaluate the long-term wear performance of alumina matrix composite (AMC) heads against alumina matrix composite inserts and alumina matrix composite heads against alumina (Al) inserts with the use of a hip-joint simulator incorporating severe swing phase joint microseparation. The wear of AMC on Al produced an average wear rate of 0.61 mm3/million cycles over the 5-million-cycle test duration. The wear of AMC on AMC produced an average wear rate of 0.16 mm3/million cycles over the 5-million-cycle test duration. Both the AMC on alumina and AMC on AMC produced significantly lower wear than previously tested HIPed alumina, where an average wear rate of 1.84 mm3/million cycles was reported over 5 million cycles. The wear mechanisms and wear debris of AMC on AMC and AMC on Al were similar to those observed in previous alumina retrieval studies with stripe wear caused by intragranular fracture and wear debris consisting of predominantly uniform 10-20-nm-sized particles and a few irregular particles up to 3 microm in size.

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A new class of materials, bone adhesives, could revolutionise the treatment of highly fragmented fractures. We present the first biological safety investigation of a bio-inspired bone adhesive. The formulation was based upon a modified calcium phosphate cement that included the amino acid phosphoserine. This material has recently been described as substantially stronger than other bioresorbable calcium phosphate cements. Four adhesive groups with the active substance (phosphoserine) and two control groups without phosphoserine were selected for in vitro and in vivo biocompatibility testing. The test groups were subject for cell viability assay and subcutaneous implantation in rats that was followed by gene expression analysis and histology assessment after 6 and 12 weeks. All adhesive groups supported the same rate of cell proliferation compared to the α-TCP control and had viability between 45-64% when compared to cell control. There was no evidence of an increased immune response or ectopic bone formation in vivo. To conclude, this bio-inspired bone adhesive has been proven to be safe, in the present study, without any harmful effects on the surrounding soft tissue.

The aim of the present study was to evaluate the soft tissue bond strength of a newly developed, monomeric, biomimetic, tissue adhesive called phosphoserine modified cement (PMC). Two types of PMCs were evaluated using lap shear strength (LSS) testing, on porcine skin: a calcium metasilicate (CS1), and alpha tricalcium phosphate (αTCP) PMC. CS1 PCM bonded strongly to skin, reaching a peak LSS of 84, 132, and 154 KPa after curing for 0.5, 1.5, and 4 h, respectively. Cyanoacrylate and fibrin glues reached an LSS of 207 kPa and 33 kPa, respectively. αTCP PMCs reached a final LSS of ≈110 kPa. In soft tissues, stronger bond strengths were obtained with αTCP PMCs containing large amounts of amino acid (70–90 mol%), in contrast to prior studies in calcified tissues (30–50 mol%). When αTCP particle size was reduced by wet milling, and for CS1 PMCs, the strongest bonding was obtained with mole ratios of 30–50% phosphoserine. While PM-CPCs behave like stiff ceramics after setting, they bond to soft tissues, and warrant further investigation as tissue adhesives, particularly at the interface between hard and soft tissues.

Background: Currently there are no standard models with which to evaluate the biomechanical performance of calcified tissue adhesives, in vivo. We present, herein, a pre-clinical murine distal femoral bone model for evaluating tissue adhesives intended for use in both osseous and osteochondral tissue reconstruction. Results: Cylindrical cores (diameter (Ø) 2 mm (mm) × 2 mm depth), containing both cancellous and cortical bone, were fractured out from the distal femur and then reattached using one of two tissue adhesives. The adhesiveness of fibrin glue (Tisseel tm ), and a novel, biocompatible, calcium phosphate-based tissue adhesive (OsStic tm ) were evaluated by pullout testing, in which glued cores were extracted and the peak force at failure recorded. The results show that Tisseel weakly bonded the metaphyseal bone cores, while OsStic produced > 30-fold higher mean peak forces at failure (7.64 Newtons (N) vs. 0.21 N). The failure modes were consistently disparate, with Tisseel failing gradually, while OsStic failed abruptly, as would be expected with a calcium-based material. Imaging of the bone/ adhesive interface with microcomputed tomography revealed that, for OsStic, failure occurred more often within cancellous bone (75% of tested samples) rather than at the adhesive interface.Conclusions: Despite the challenges associated with biomechanical testing in small rodent models the preclinical ex-vivo test model presented herein is both sensitive and accurate. It enabled differences in tissue adhesive strength to be quantified even for very small osseous fragments (<Ø4mm). Importantly, this model can easily be scaled to larger animals and adapted to fracture fragment fixation in human bone. The present model is also compatible with other long-term in vivo evaluation methods (i.e. in vivo imaging, histological analysis, etc.).