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Bone & Joint Research
Vol. 5, Issue 4 | Pages 106 - 115
1 Apr 2016
Gruber HE Ode G Hoelscher G Ingram J Bethea S Bosse MJ

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483


Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1


Bone & Joint Research
Vol. 6, Issue 3 | Pages 144 - 153
1 Mar 2017
Kharwadkar N Mayne B Lawrence JE Khanduja V

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Methods

We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 423 - 432
1 Jul 2017
van der Stok J Hartholt KA Schoenmakers DAL Arts JJC

Objectives

The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery.

Methods

A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 216 - 223
1 Apr 2017
Ang BFH Chen JY Yew AKS Chua SK Chou SM Chia SL Koh JSB Howe TS

Objectives

External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF).

Methods

A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 187 - 192
1 Jun 2014
Penn-Barwell JG Rand BCC Brown KV Wenke JC

Objectives

The purpose of this study was to refine an accepted contaminated rat femur defect model to result in an infection rate of approximately 50%. This threshold will allow examination of treatments aimed at reducing infection in open fractures with less risk of type II error.

Methods

Defects were created in the stablised femurs of anaethetised rats, contaminated with Staphylococcus aureus and then debrided and irrigated six hours later. After 14 days, the bone and implants were harvested for separate microbiological analysis. This basic model was developed in several studies by varying the quantity of bacterial inoculation, introducing various doses of systemic antibiotics with and without local antibiotics.


Bone & Joint Research
Vol. 1, Issue 6 | Pages 118 - 124
1 Jun 2012
Grawe B Le T Williamson S Archdeacon A Zardiackas L

Objectives

We aimed to further evaluate the biomechanical characteristics of two locking screws versus three standard bicortical screws in synthetic models of normal and osteoporotic bone.

Methods

Synthetic tubular bone models representing normal bone density and osteoporotic bone density were used. Artificial fracture gaps of 1 cm were created in each specimen before fixation with one of two constructs: 1) two locking screws using a five-hole locking compression plate (LCP) plate; or 2) three non-locking screws with a seven-hole LCP plate across each side of the fracture gap. The stiffness, maximum displacement, mode of failure and number of cycles to failure were recorded under progressive cyclic torsional and eccentric axial loading.


Bone & Joint Research
Vol. 1, Issue 4 | Pages 50 - 55
1 Apr 2012
O’Neill F Condon F McGloughlin T Lenehan B Coffey C Walsh M

Introduction

The objective of this study was to determine if a synthetic bone substitute would provide results similar to bone from osteoporotic femoral heads during in vitro testing with orthopaedic implants. If the synthetic material could produce results similar to those of the osteoporotic bone, it could reduce or eliminate the need for testing of implants on bone.

Methods

Pushout studies were performed with the dynamic hip screw (DHS) and the DHS Blade in both cadaveric femoral heads and artificial bone substitutes in the form of polyurethane foam blocks of different density. The pushout studies were performed as a means of comparing the force displacement curves produced by each implant within each material.


Bone & Joint Research
Vol. 2, Issue 3 | Pages 51 - 57
1 Mar 2013
Sullivan MP Torres SJ Mehta S Ahn J

Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones.