Introduction

Anatomical reduction of articular fragments in tibial plateau fractures often leads to a void and there is a need to fill dead space and support the articular fragment. MIIG X3 is marketed as high strength injectable graft, which resorbs and remodels fast. Efficacy and complications related to the use of this bone graft substitute were evaluated in this study

Introduction

The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material.

A total of 20 patients with a depressed fracture of the lateral tibial plateau (Schatzker II or III) who would undergo open reduction and internal fixation were randomised to have the metaphyseal void in the bone filled with either porous titanium granules or autograft bone. Radiographs were undertaken within one week, after six weeks, three months, six months, and after 12 months.

The primary outcome measure was recurrent depression of the joint surface: a secondary outcome was the duration of surgery.

The risk of recurrent depression of the joint surface was lower (p < 0.001) and the operating time less (p < 0.002) when titanium granules were used.

The indication is that it is therefore beneficial to use porous titanium granules than autograft bone to fill the void created by reducing a depressed fracture of the lateral tibial plateau. There is no donor site morbidity, the operating time is shorter and the risk of recurrent depression of the articular surface is less.

Cite this article: Bone Joint J 2015; 97-B:836–41

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

Osteoinductive bone substitutes are in their developmental infancy and a paucity of effective grafts options persists despite clinical demand. Bone mineral substitutes such as hydroxyapatite cause minimal biological activity when compared to osteoinductive systems present biological growth factors in order to drive bone regeneration. We have previously demonstrated the in-vitro efficacy of a bioengineered system at presenting growth factors at ultra low-doses. This study aimed to translate this growth factor delivery system towards a clinically applicable implant. Osteoinductive surfaces were engineered using plasma polymerisation of poly(ethyl acrylate) onto base materials followed by adsorption of fibronectin protein and subsequently growth factor (BMP-2). Biological activity following ethylene oxide (EO) sterilisation was evaluated using ELISAs targeted against BMP-2, cell differentiation studies and atomic force microscopy. Scaffolds were 3D printed using polycaprolactone/hydroxyapatite composites and mechanically tested using a linear compression models to calculate stress/strain. In-vivo analysis was performed using a critical defect model in 23 mice over an 8 week period. Bone formation was assessed using microCT and histological analysis. Finally, a computer modelling process was developed to convert patient CT images into surface models, then formatted into 3D-printable scaffolds to fill critical defects. Following EO sterilisation, there was no change in scaffold surface and persistent availability of growth factors. Scaffolds showed adequate porosity for cell migration with mechanical stiffness similar to cancellous bone. Finally, the in vivo murine model demonstrated rapid bone formation with evidence of trabecular remodelling in samples presenting growth factors compared to controls

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. The need for a novel, cost effective treatment option for osteochondral defects has therefore never been greater. As an emerging technology, three-dimensional (3D) bioprinting has the capacity to deposit cells, extracellular matrices and other biological materials in user-defined patterns to build complex tissue constructs from the “bottom up”. Through use of extrusion bioprinting and fused deposition modelling (FDM) 3D printing, porous 3D scaffolds were successfully created in this study from hydrogels and synthetic polymers. Mesenchymal stem cells (MSCs) seeded onto polycaprolactone scaffolds with defined pore sizes and porosity maintained viability over a 7-day period, with addition of alginate hydrogel and scaffold surface treatment with NaOH increasing cell adhesion and viability. MSC-laden alginate constructs produced via extrusion bioprinting also maintained structural integrity and cell viability over 7 days in vitro culture. Growth within osteogenic media resulted in successful osteogenic differentiation of MSCs within scaffolds compared to controls (p<0.001). MSC spheroids were also successfully created and bioprinted within a novel, supramolecular hydrogel with tunable stiffness. In conclusion, 3D constructs capable of supporting osteogenic differentiation of MSCs were biofabricated via FDM and extrusion bioprinting. Future work will look to increase osteochondral construct size and complexity, whilst maintaining cell viability

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites

Aims

Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

Background:. Segmental defects of long bones are notoriously demanding and difficult to treat. We evaluate nine cases where the Masquelet induced membrane technique to substitute bone loss has been used. We discuss the method compared to other types of bone reconstruction and share our tips and tricks to reduce treatment time and improve patient comfort. Method:. Eight patients (nine injuries) operated between 2011 and 2014 were included. Four were infected. Outcome was time-to weight-bearing, consolidation, complications, bone grafting. Results:. All patients were weight bearing fully after 270 days. Mean time to weight bearing was 225 days. Time to full weight bearing was shorter in patients where nails were used to stabilize the construct: median 115 (range 0–268) compared to plates: median 244 (range 219–271). All but two cases went on to full consolidation. Three cases needed grafting, one was misaligned. There were no amputations, no persistent infections, and no implant failures. Discussion:. The induced membrane technique is a relevant alternative to traditional bone substitution in select cases, yet somewhat unpredictable in its course and prolonged immobilisation is often required. Conclusion:. Nailing seems to improve the outcome by reducing treatment time and volume of bone graft needed and should be considered when feasible

The use of external fixation in the management of long bone fractures has long been recognised. The aim of this study was to compare 3 differing constructs of Hoffman-2 and Hoffman-3 External Fixator systems to assess which potentially withstood the greatest load. Three different constructs (2, 3 and 4-bar) of Hoffman 2 and 3 External Fixation systems were tested. A UHMWPE tube was utilised as a bone substitute to construct a biomechanically reproducible model which could be tested on an MTS testing jig. Each construct was loaded to 3, 5, 8, 12 and 15mm of displacement at the fracture gap. Each construct was cyclically loaded 200 times for each test and repeated 5 times. The results demonstrate that the Hoffman-3 configurations withstood a load of at least twice that of the Hoffman 2 configurations across all displacements. Using a 2-way ANOVA test at all displacements the 2-bar configuration withstood greater load than the 3 bar (P<0.0001). With Hoffman 2 the 2-bar configuration withstood a greater load than the 4 bar diamond configuration. These results demonstrate that Hoffman-3 External Fixation Device has a greater axial loading capacity than its Hoffman-2 predecessor

Background. The inherently high stiffness of locked plate constructs is increasingly recognized as a potential cause of deficient healing observed in patients with periarticular locked plating systems. The objective of this study is to perform a biomechanical comparison of distal femur locked plating systems. Methods. Biomechanical study using bone substitutes in a distal femur fracture model (OTA/AO 33-A3). Four different locked plate fixation systems were compared (AxSOS, LCP, PERI-LOC, POLYAX). Eight bone implant constructs of each plating system were evaluated in a multiple testing model to examine static failure, stiffness under static and cyclic loading and cyclic fatigue. Results. The implant systems made of titanium alloy (POLYAX & LCP) supported smaller torsional stiffness values under static loads and smaller axial stiffness values under cyclic loads compared with the implant systems made of stainless steel (PERI-LOC & AxSOS). All bone implant constructs reached the cyclic failure criterion of 10 degrees displacement at the fracture area within the third load level (>50000 cycles) except for the LCP which failed earlier. Conclusion. The tested four different locked plating systems differ significantly in terms of stiffness and load to failure. Two of the clinical available systems differed almost 100% in stiffness values. And one system differed almost 100% in fatigue strength. For clinical use, this knowledge is essential for the practicing orthopaedic surgeon

Aims

Open reduction and plate fixation (ORPF) for displaced proximal humerus fractures can achieve reliably good long-term outcomes. However, a minority of patients have persistent pain and stiffness after surgery and may benefit from open arthrolysis, subacromial decompression, and removal of metalwork (ADROM). The long-term results of ADROM remain unknown; we aimed to assess outcomes of patients undergoing this procedure for stiffness following ORPF, and assess predictors of poor outcome.

Posterolateral spinal fusion (PSLSF) in rabbits is a challenging model for bone substitutes because the transverse processes are extremely thin and the space to be filled with bone is greater than critical and meiopragic in terms of vascularity. Several investigators have shown beneficial effects of PRP in bone and soft-tissue healing processes. However, controversial results have been reported in clinical setting analysing the effectiveness of PRP. Aim of the present study was to test the effectiveness of PRP in experimental model of PLSF in rabbits. MATERIAL AND METHODS. 20 White females New Zeland Rabbits were used. Seven rabbits (Group 1) had PRP plus carrier on the right side (Group 1A) and plus carrier and fresh bone marrow on the left side (Group 1B). Seven rabbits (Group 2) had carrier alone on the right side (Group 2A) and carrier plus fresh bone marrow on the left side (Group 2B). Six rabbits (Group 3) had sham operation on both right and left sides. Animals were sacrificed 6 months after surgery and the lumbar spine submitted to radiolographic and histologic analysis. Vascular density (VD) was also assessed in the different zone of the grafted material. RESULTS. Radiographs showed a complete fusion in 83% of group 1A and in 83% of group 1B, and in 86% of group 2A and 2B. Pseudarthrosis or non union, was observed in 1 specimen of group 1B and 2A and in all specimens of group 3 (sham). In contrast to radiographic results, no specimen showed a complete bony bridge between the transverse processes on histologic analysis. VD was significantly greater in the periapophyseal compared to the interapophyseal region of the graft material. However, no significant difference was found in the VD between groups. CONCLUSIONS. In this study PRP alone, or augmented with fresh bone marrow, failed to induce a histologically proved bony fusion in the PLSF model. Factors which may influence the effectiveness of PRP should be further addressed before applying PRP in the clinical setting

Bioactive glasses (BAGs) are bone substitutes with bone bonding, angiogenesis promoting and antibacterial properties. The bioactive process leading to bone bonding has been described as a sequence of reactions in the glass and at its surface. Implantation of the glass is followed by a rapid exchange of Na+ in the glass with H+ and H3O+ from the surrounding tissue, leading to the formation of silanol (SiOH) groups at the glass surface. Due to migration of Ca2+ and PO43− groups to the surface and cystallization, a CaO-P2O5 hydroxyapatite (HA) layer is formed on top of the Si-rich layer. Finally, cell interactions with the HA layer subsequently initiate the bone forming pathway. The rapid increase in pH and the subsequent osmotic effect caused by dissolution of the glass have been suggested to partly explain the antibacterial properties observed for BAGs. Comparing bactericidal effects of different BAGs, BAG-S53P4 has been shown to be the most effective, with the fastest killing or growth inhibitory effect. This antibacterial effect has been observed in vitro for all pathogens tested, including the most important aerobic and anaerobic pathogens, as well as very resistant bacteria. In a multicentre study in 2007–2009, BAG-S53P4 was used as bone graft substitute in treatment of osteomyelitis. Eleven patients (nine males, two females) with a radiologically diagnosed osteomyelitis in the lower extremity (N=10) and in the spine (N-1) participated. In the operation, the infected bone and the soft tissue were removed, and the cavitary bone defects were filled with BAG-S53P4 (BonAlive™, Bonalive Biomaterials Ltd., Finland). In four patients, muscle flaps were used as part of the treatment. Eight patients were treated in a one-stage procedure. Kanamycin granules were used in one patient and Garamycin granules (Septocol ®) in two patients. Patient data were obtained from hospital patient' records until August 2010, resulting in a mean follow-up period of 29 months (range 15–43). BAG-S53P4 was well tolerated; no BAG-related adverse effects were seen in any patient. The use of BAG-S53P4 as a bone graft substitute resulted in a fast recovery. Long-term clinical outcome was good or excellent in ten of eleven patients. These primary results indicate that BAG-S53P4 can be considered as a good and usable material in treatment of osteomyelitis. After this study BAG-S53P4 has been used in several other patients with very promising results

Introduction. The combined incubation of a composite scaffold with bone marrow stromal cells in a perfusion bioreactor could make up a novel hybrid graft material with optimal properties for early fixation of implant to bone. The aim of this study was to create a bioreactor activated graft (BAG) material, which could induce early implant fixation similar to that of allograft. Two porous scaffold materials incubated with cells in a perfusion bioreactor were tested in this study. Methods and Materials. Two groups of 8 skeletally mature female sheep were anaesthetized before aspiration of bone marrow from the iliac crest. For both groups, mononuclear cells were isolated, and injected into a perfusion bioreactor (Millenium Biologix AG, Switzerland). Scaffold granules Ø∼900–1500 μm, ∼88% porosity) in group 1, consisted of hydroxyapatite (HA, 70%) with -tricalcium-phosphate (−TCP, 30%) (Danish Technological Institute, Denmark). The granules were coated with poly-lactic acid (PLA) 12%, in order to increase the mechanical strength of the material (Phusis, France). Scaffold granules Ø∼900–1400 μm, 80% porosity) in group 2 consisted of pure HA/-TCP (Fin Ceramica, Italy). For both groups, cells were incubated in the bioreactor for 2 weeks. Fresh culture medium supplemented with dexamethasone and ascorbic-acid was added every third or fourth day. Porous titanium alloy implants with diameter=length=10mm (Biomet, USA) were inserted bilaterally in each of the distal femurs of the sheep; thus 4 implants in each sheep. The concentric gap (2 mm) surrounding the implant was filled with 1) BAG (autogenous), 2) granules, 3) granules+bone marrow aspirate (BMA, autologous) or 4) allograft. The sheep were euthanized after 6 weeks. Distal femurs were removed and implant-bone samples were divided in two parts. The superficial part was used for mechanical testing and micro-CT scanning, and the profound part for histomorphometry. Push-out tests were performed on an 858 Bionix MTS hydraulic materials testing machine. Shear mechanical properties between implant and newly generated bone were calculated to assess implant fixation. Results were assessed by One-way ANOVA. P-values less than 0.05 were considered significant. Results. One sheep in group 1 had to be euthanized after 4 weeks (excluded). One implant in each group was loosened and could not undergo push-out test (excluded). Group 1: No significant differences regarding failure energy (kJ/m2, p=0.44) or ultimate shear strength (MPa, p=0.17) could be seen. Shear stiffness (MPa) was significantly higher for the allograft group (p=0.04). Group 2: No significant differences regarding failure energy (p=0.11) or shear stiffness (p=0.52) could be seen. Ultimate shear strength was significantly higher for allograft (p=0.04). Results from μ-CT scanning and histomorphometry are pending. Discussion and Conclusion. The present study shows a possible effect of bioreactor activated bone substitute on early implant fixation. We are currently working on bone microarchitecture surrounding implant and histomorphometry. These results will aid in determining if BAG could make up a promising alternative for allograft as bone graft material

Aims

To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes.

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.

Aims

This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).

Over a five-year period, adult patients with marginal impaction of acetabular fractures were identified from a registry of patients who underwent acetabular reconstruction in two tertiary referral centres. Fractures were classified according to the system of Judet and Letournel. A topographic classification to describe the extent of articular impaction was used, dividing the joint surface into superior, middle and inferior thirds. Demographic information, hospitalisation and surgery-related complications, functional (EuroQol 5-D) and radiological outcome according to Matta’s criteria were recorded and analysed. In all, 60 patients (57 men, three women) with a mean age of 41 years (18 to 72) were available at a mean follow-up of 48 months (24 to 206). The quality of the reduction was ‘anatomical’ in 44 hips (73.3%) and ‘imperfect’ in 16 (26.7%). The originally achieved anatomical reduction was lost in12 patients (25.8%). Radiologically, 33 hips (55%) were graded as ‘excellent’, 11 (18.3%) as ‘good’, one (1.7%) as ‘fair’ and 15 (25%) as ‘poor’. A total of 11 further operations were required in 11 cases, of which six were total hip replacements.

Univariate linear regression analysis of the functional outcome showed that factors associated with worse pain were increasing age and an inferior location of the impaction. Elevation of the articular impaction leads to joint preservation with satisfactory overall medium-term functional results, but secondary collapse is likely to occur in some patients.

Cite this article: Bone Joint J 2013;95-B:230–8.

This study aimed to determine the long-term functional, clinical and radiological outcomes in patients with Schatzker IV to VI fractures of the tibial plateau treated with an Ilizarov frame. Clinical, functional and radiological assessment was carried out at a minimum of one year post-operatively. A cohort of 105 patients (62 men, 43 women) with a mean age of 49 years (15 to 87) and a mean follow-up of 7.8 years (1 to 19) were reviewed. There were 18 type IV, 10 type V and 77 type VI fractures. All fractures united with a mean time to union of 20.1 weeks (10.6 to 42.3). No patient developed a deep infection. The median range of movement (ROM) of the knee was 110^o and the median Iowa score was 85.

Our study demonstrates good long-term functional outcome with no deep infection; spanning the knee had no detrimental effect on the ROM or functional outcome.

High-energy fractures of the tibial plateau may be treated effectively with a fine wire Ilizarov fixator.

Cite this article: Bone Joint J 2015;97-B:1693–7.