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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 30 - 30
2 Jan 2024
Procter P Hulsart-Billström G Alves A Pujari-Palmer M Wenner D Insley G Engqvist H Larsson S Pippenger B Bossard D
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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.

Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 99 - 99
1 Mar 2021
Procter P Hulsart-Billstrom G Insley G Pujari-Palmer M Wenner D Engqvist H Larsson S
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An ex vivo biomechanical test model for evaluating a novel bone adhesive has been developed. However, at day 1 in the in vivo pilot, high blood flow forced the study to halt until the solution presented here was developed.

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 ex vivo study produced mean peak tensile loads of 7.63N SD 2.39N (n=8, 4 rats 8 femurs). Whilst the mean peak tensile loads in the day 1 in vivo pilot were significantly lower 1.53N SD1.57 (n=8, 6 rats 8 femurs − 4 used for other tests). The subsequent layered adhesive bone cores showed a mean peak tensile force of 6.79N SD =3.13 (n=8, 4 rats 8 femurs). 7/8 failed at the bone to glue interface. This is the first successful demonstration of bonding bone in vivo for this class of adhesives.

The development of a double adhesive method of fixing a bone core in the distal femur enabled mean peak tensile forces to be achieved in vivo at 24 hours that were comparable with the ex vivo results previously demonstrated. This method supports application in further animal series and over longer time scales. Biomaterials researchers that intend to use gel or paste like preparations in distal femur defects in the rat should be aware of the risks of biomaterial displacement by local blood flow.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 25 - 25
1 Sep 2019
Williams F Palmer M Tsepilov Y Freidin M Boer C Yau M Evans D Gelemanovic A Bartz T Nethander M Arbeeva L Karssen L Neogi T Campbell A Mellstrom D Ohlsson C Marshall L Orwoll E Uitterlinden A Rotter J Lauc G Psaty B Karlsson M Lane N Jarvik G Polasek O Hochberg M Jordan J van Meurs J Jackson R Nielson C Mitchell B Smith B Hayward C Smith N Aulchenko Y Suri P
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Purpose

Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied.

Methods

CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10–7) & genome-wide significant (p<5×10–8) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 83 - 83
1 Nov 2018
Procter P Insley G Engqvist H Pujari-Palmer M Billstrom GH Larsson S
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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.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_12 | Pages 2 - 2
1 Jun 2017
Crainic A Callisti M Palmer M Cook R
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Metallic contacts in hip replacements are susceptible to wear and corrosion processes which lead to the release of particles and metal ions. Adverse local tissue reactions (ALTRs) and systemic manifestations to solid and soluble debris can be debilitating for the patients. It is believed that particles originating from CoCrMo taper junctions trigger more severe body reactions compared to debris from MoM hip bearings. The body's reaction is highly dependent on particle characteristics, such as size, morphology, composition and aggregation state, which can reflect the specific wear and corrosion conditions at the site of release.

Here we proposed to investigate wear and corrosion flakes collected from around CoCrMo tapers at the time of revision. The particles were initially characterised with scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). This revealed the microstructure of the corrosion products, which appeared to be made of smaller metallic aggregates, entrapped in a biological matrix. The in depth characterisation of the particles released from the organo-metallic composite, was performed with transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM), both fitted with EDX. The investigation revealed clusters and individual nanoparticles, as small as 3 nm, which represent the building blocks of the large corrosion flakes, reported and characterised in the past mainly with low resolution microscopy techniques. The majority of the particles consisted of Cr and O, potentially in the form of chromium oxides, with little evidence of Co and Mo. Particles size distribution (PSD) provided by STEM and TEM characterisation showed statistically different results. The STEM technique was able to resolve tiny particles found in close proximity and provided a PSD shift towards the smaller end of the size range.

The study is the first to show microscopy evidence of Cr rich nanoparticles (3–60 nm) released in vivo from the modular taper interface, which can have important health implications caused by their increased potential to disseminate and corrode within the body.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_3 | Pages 114 - 114
1 Feb 2017
Favre P King E Palmer M Eldemerdash A Bischoff J Lawton J
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INTRODUCTION

Aseptic loosening is the most common failure mode for Total Elbow Arthroplasty (TEA) and is considered to be associated with accelerated polyethylene bearing wear [1, 2]. This study aimed to evaluate three commercially available implant designs under loads associated with daily living. The hypothesis was that more recent designs (Discovery and Nexel) provide greater articular contact areas resulting in lower polyethylene stresses compared to the Coonrad/Morrey (CM).

METHODS

Motion tracking was performed on a healthy volunteer during elbow flexion at 0, 45, and 90° shoulder abduction because most daily activities occur with some shoulder abduction [3] resulting in varus stress about the elbow. This kinematic data was used in an OpenSim upper extremity musculoskeletal model [4] to estimate muscle and joint reaction loads with 5lb in hand, consistent with the common clinical restrictions following TEA.

Computer aided assemblies of the smallest size implants for each system were imported to ANSYS for finite element analysis. Metallic components were treated as rigid and polyethylene components were modeled using a nonlinear elastoplastic constitutive model calibrated to material data. Articular contacts were frictional. Physiologic joint reaction forces and moments quantified in OpenSim were applied and the resulting peak articular contact area and peak bearing von Mises stresses were assessed.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 27 - 27
1 Sep 2012
Bajada S Roberts G Gwyn R Palmer M Fanarof H Ennis O
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Introduction

Neck of femur (NOF) fractures are one of the predominant reasons for hospital admissions in patients >65 year. These fractures are associated with a poor outcome; end to independent living in 60% of patients and a 6 month mortality of 30%. Previous studies have shown show elements of under/mal-nutrition on admission. In addition, their nutritional status shows some deterioration thereafter. The aim of this present study is to examine if the nutritional status of patients with NOF fracture admitted at our institution is associated with a larger post-operative haemoglobin drop. This is compared to an independent living age matched control group from the same geographical area.

Methods

A retrospective audit of pathology results for three hundred fracture patients (n = 300) and one hundred age matched home living group pre-assessed of total hip replacement (n = 100). Total serum protein, albumin, total lymphocyte count levels were determined at the time of admission to assess nutritional status. Pre/post-operative haemoglobin, resultant haemoglobin drop, and 6 month mortality was assessed in NOF fracture patients. The nutritional parameters were correlated with the haemoglobin levels and mortality.