Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model. A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments.
Calcium phosphates are among the most commonly used bone graft substitute materials. Compositions containing predominantly monetite (∼84.7%) with smaller additions of beta-tricalcium phosphate (β-TCP; ∼8.3%) and calcium pyrophosphate (Ca-PP; ∼6.8%) have previously been demonstrated to exhibit osteoinductive properties. Such a multi-component calcium phosphate bioceramic was fashioned in the form of hollowed-out, dome-shaped devices (15 mm diameter, 4 mm height), each reinforced with a 3D printed Ti6Al4V ELI frame. With the aim to induce bone formation beyond the skeletal envelope, these devices were investigated in vivo using a sheep (Ovis aries) occipital bone model. The bioceramic composition was prepared from a mixture of β-TCP/dicalcium pyrophosphate and monocalcium phosphate monohydrate powders mixed with glycerol. The Ti6Al4V ELI frame was positioned into a dome-shaped mould and bioceramic paste was poured over the frame and allowed to set, in sterile water, prior to removal from the mould. In adult female sheep (n=7), the devices were positioned directly over the bone and stabilised using self-drilling screws. After 52 weeks, the devices were retrieved, resin embedded, and used for X-ray micro-computed tomography (micro-CT), histology, backscattered electron scanning electron microscopy (BSE-SEM), energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR).Introduction and Objective
Materials and Methods
An The profuse bleeding after bone core removal affected the bond strength and was reflected in the lower mean peak value 1.53N. After considering several options, we were successful in sealing the source of blood flow by pressing adhesive into place after bone core removal. After the initial adhesive had cured additional adhesive was used to secure the bone core in place. The animals were sacrificed after 24 h and a tensile test was undertaken on the bone core to failure. The The development of a double adhesive method of fixing a bone core in the distal femur enabled mean peak tensile forces to be achieved
There are clinical situations in fracture repair, e.g. osteochondral fragments, where current implant hardware is insufficient. The proposition of an adhesive enabling fixation and healing has been considered but no successful candidate has emerged thus far. The many preclinical and few clinical attempts include fibrin glue, mussel adhesive and even “Kryptonite” (US bone void filler). The most promising recent attempts are based on phosphorylating amino acids, part of a common cellular adhesion mechanism linking mussels, caddis fly larvae, and mammals. Rapid high bond strength development in the wetted fatty environment of fractured bone, that is sustained during biological healing, is challenging to prove both safety and efficacy. Additionally, there are no “predicate” preclinical animal and human models which led the authors to develop novel evaluations for an adhesive candidate “OsStictm” based on calcium salts and amino acids. Adhesive formulations were evaluated in both soft (6/12 weeks) and hard tissue (3,7,10,14 & 42 days) safety studies in murine models. The feasibility of a novel adhesiveness test, initially proven in murine cadaver femoral bone, is being assessed in-vivo (3,7,10,14 & 42 days) in bilateral implantations with a standard tissue glue as the control. In parallel an ex-vivo human bone model using freshly harvested human donor bone is under development to underwrite the eventual clinical application of such an adhesive. This is part of a risk mitigation project bridging between laboratory biomaterial characterisation and a commercial biomaterial development where safety and effectiveness have to meet today´s new medical device requirements.
The chemistry, amount, morphology, and size distribution of wear debris from silicon nitride coatings generated in the bearing surface can potentially reduce the negative biological response and increase the longevity compared to conventional materials in joint replacements. Total hip implants have a high success rate at 15 years of implantation, but few survive over 25 years. At present, revisions are mostly due to aseptic loosening, believed to mainly be caused by the biological response to wear debris generated in the joint bearing. For the polymer liners the size of the wear debris determines the biological response, while for metal bearing surfaces a limitation is the metal ion release. When ceramics are used, the wear debris is in general small and mechanical factors may be the main cause for failure. A more recent, experimental alternative is to let the well-known metallic substrate serve as the soft, tough bulk, and additionally apply a hard and smooth ceramic coating. In this way a lower wear rate and reduced metal ion release could be obtained. Furthermore, the chosen composition, silicon nitride (SixNy), contains no detrimental ions, and silicon nitride debris has been shown to slowly dissolve in aqueous medium. Altogether, it can potentially increase the longevity of the implant. However, the debris from SixNy coatings has not yet been characterised. In this study, a wear model test was performed to generate wear debris from SixNy coatings. The debris was characterised using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) in combination with computational calculations.Summary Statement
Introduction
Interbody fusion aims to treat painful disc disease by demobilising the spinal segment through the use of an interbody fusion device (IFD). Diminished contact area at the endplate interface raises the risk of device subsidence, particularly in osteoporosis patients. The aim of the study was to ascertain whether vertebral body (VB) cement augmentation would reduce IFD subsidence following dynamic loading. Twenty-four human two-vertebra motion segments (T6–T11) were implanted with an IFD and distributed into three groups; a control with no cement augmentation; a second with PMMA augmentation; and a third group with calcium phosphate (CP) cement augmentation. Dynamic cyclic compression was applied at 1Hz for 24 hours in a specimen specific manner. Subsidence magnitude was calculated from pre and post-test micro-CT scans. The inferior VB analysis showed significantly increased subsidence in the control group (5.0±3.7mm) over both PMMA (1.6±1.5mm, p=.034) and CP (1.0±1.1mm, p=.010) cohorts. Subsidence in the superior VB to the index level showed no significant differences (control 1.6±3.0mm, PMMA 2.1±1.5mm, CP 2.2±1.2mm, p=.811). In the control group, the majority of subsidence occurred in the lower VB with the upper VB displaying little or no subsidence, which reflects the weaker nature of the superior endplate. Subsidence was significantly reduced in the lower VB when both levels were reinforced regardless of cement type. Both PMMA and CP cement augmentation significantly affected IFD subsidence by increasing VB strength within the motion segment, indicating that this may be a useful method for widening indications for surgical interventions in osteoporotic patients.
