Aims

To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).

Aims

Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Aims

Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Post-traumatic elbow stiffness is a disabling condition that remains challenging for upper limb surgeons. Open elbow arthrolysis is commonly used for the treatment of stiff elbow when conservative therapy has failed. Multiple questions commonly arise from surgeons who deal with this disease. These include whether the patient has post-traumatic stiff elbow, how to evaluate the problem, when surgery is appropriate, how to perform an excellent arthrolysis, what the optimal postoperative rehabilitation is, and how to prevent or reduce the incidence of complications. Following these questions, this review provides an update and overview of post-traumatic elbow stiffness with respect to the diagnosis, preoperative evaluation, arthrolysis strategies, postoperative rehabilitation, and prevention of complications, aiming to provide a complete diagnosis and treatment path.

Cite this article: Bone Joint Open 2020;1-9:576–584.

Aims

Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients.

Aims

Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA).

Aims

Total ankle arthroplasty (TAA) surgery is complex and attracts a wide variety of complications. The literature lacks consistency in reporting adverse events and complications. The aim of this article is to provide a comprehensive analysis of each of these complications from a literature review, and to compare them with rates from our Unit, to aid clinicians with the process of informed consent.

Aims

Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature.

Aims

The aim of this study was to assess the efficacy of non-selective and selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing heterotopic ossification (HO) after total hip arthroplasty (THA).

Aims

To evaluate the outcomes of cemented total hip arthroplasty (THA) following a fracture of the acetabulum, with evaluation of risk factors and comparison with a patient group with no history of fracture.

Aims

The purpose of this study was to determine the sensitivity, specificity and predictive values of previously reported thresholds of proximal translation and sagittal rotation of cementless acetabular components used for revision total hip arthroplasty (THA) at various times during early follow-up.

Bone tissue engineering constructs (BTEC) combining natural resorbable osteoconductive scaffolds and mesenchymal stem cells (MSCs) have given promising results to repair critical size bone defect. Yet, results remain inconsistent. Adjonction of an osteoinductive factor to these BTEC, such as rh-BMP-2, to improve bone healing, seems to be a relevant strategy. However, currently supraphysiological dose of this protein are used and can lead to adverse effects such as inflammation, ectopic bone and/or bone cyst formation. Interestingly, in a preliminary study conducted in ectopic site in a murine model, a synergistic effect on bone formation was observed only when a low dose of rh-BMP-2 was associated with MSCs-seeded coral scaffolds but not with a high dose. The objective of the study was then to evaluate a BTEC combining coral scaffold, MSCs and a low dose of rh-BMP-2 in a large animal model of clinical relevance. Sixteen sheep were used for this study. MSCs were isolated from an aspirate of bone marrow harvested from the iliac crest of each sheep receiving BTEC with MSCs, cultivated and seeded on Acroporacoral scaffolds one week before implantation. Rh-BMP-2, used at two different doses (low dose: 68μg/defect and high dose: 680μg/defect), was diluted and absorbed on Acroporacoral scaffold one day before implantation. Metatarsal segmental bone defects (25 mm) were made in the left metatarsal bone of the sheep, stabilized by plate fixation, and filled with Acroporacoral scaffolds loaded with either (i) MSCs and a low dose of rh-BMP-2 (Group 1;n=6), (ii) a low dose of rh-BMP-2 (Group 2;n=5), (iii) a high dose of rh-BMP-2 (Group 3;n=5). Standard radiographs were taken after each surgery and each month until sheep sacrifice, 4 months postoperatively. Bone healing and scaffold resorption were assessed by micro-computed-tomography (μCT) and histomorphometry. Results were compared to a historical control group in which coral scaffolds were loaded with MSCs. Bone volumes (BV) evaluated by μCT and bone surfaces (BS) evaluated by histomorphometry did not differ between groups (BV: 1914±870, 1737±841, 1894±1028 and 1835±1342 mm. 3. ; BS: 25,41±14,25, 19,85±8,31, 25,54±16,98 and 26,08±22,52 %; groups 1, 2, 3 and control respectively); however, an higher bone union was observed in group 1 compared to the others (3, 1, 2 and 2 sheep with bone union in groups 1, 2, 3 and control respectively). No histological abnormalities were observed in any group. Coral resorption was almost complete in all specimens. No significant difference in coral volumes and coral surfaces was observed between groups. A trend towards a higher variability in coral resorption was noted in group 1 compared to the others. There seems to be a benefit to associate low dose of rh-BMP-2 with MSCs-seeded coral scaffolds as this strategy allowed an increase of bone unions in our model. Yet, results remain inconsistent. Although, defective coupling between scaffold resorption and bone formation impaired bone healing in some animals, adjunction of rh-BMP-2 (even at low dose) to CSMs loaded construct is a promising strategy for bone tissue engineering

We retrospectively reviewed 89 consecutive patients (45 men and 44 women) with a mean age at the time of injury of 58 years (18 to 97) who had undergone external fixation after sustaining a unilateral fracture of the distal humerus. Our objectives were to determine the incidence of heterotopic ossification (HO); identify risk factors associated with the development of HO; and characterise the location, severity and resultant functional impairment attributable to the presence of HO.

HO was identified in 37 elbows (42%), mostly around the humerus and along the course of the medial collateral ligament. HO was hazy immature in five elbows (13.5%), mature discrete in 20 (54%), extensive mature in 10 (27%), and complete bone bridges were present in two elbows (5.5%). Mild functional impairment occurred in eight patients, moderate in 27 and severe in two. HO was associated with less extension (p = 0.032) and less overall flexion-to-extension movement (p = 0.022); the flexion-to-extension arc was < 100º in 21 elbows (57%) with HO compared with 18 elbows (35%) without HO (p = 0.03). HO was removed surgically in seven elbows.

The development of HO was significantly associated with sustaining a head injury (p = 0.015), delayed internal fixation (p = 0.027), the method of fracture fixation (p = 0.039) and the use of bone graft or substitute (p = 0.02).HO continues to be a substantial complication after internal fixation for distal humerus fractures.

Cite this article: Bone Joint J 2014;96-B:1681–7.

Summary. In this study, OsteoAMP® bone graft showed superior fusion rates as compared to rhBMP-2 at all timepoints (p<0.004). Additionally, OsteoAMP® bone graft had >80% few adverse events as compared to rhBMP-2. Introduction. Adverse events and complications related to use of rhBMP-2 have raised many ethical, legal, and reimbursement concerns for surgeons. OsteoAMP® bone graft is an allograft derived growth factor, rich in osteoinductive, angiogenic, and mitogenic proteins. The following data displays a blinded, multi -center study evaluating and comparing fusion outcomes between rhBMP-2 and OsteoAMP® bone graft. Patients & Methods. A total of 254 consecutive patients (383 total levels) were treated with TLIF or LLIF spine fusion procedures. A group of 70 patients (53.3 ± 11.1 y/o) were treated with rhBMP-2 (Infuse®/Inductos®, Medtronic) and local bone inside of a PEEK interbody cage with an average of 1.44 levels per surgery. A group of 184 patients (60.5 ± 13.1 y/o) were treated with OsteoAMP® (Advanced Biologics) and local bone inside of a PEEK interbody cage with an average of 1.53 levels per surgery. Fusion assessments were made by a blinded independent radiologist based on radiograph and CT images at 6w, 3m, 6m, 12m, and 18m follow up. Radiographically evident adverse events were also assessed in a blinded manner by an independent radiologist. Results. Overall fusion analysis showed superiority in efficacy of OsteoAMP® over rhBMP-2 at all time points (p<0.004). Use of rhBMP-2 produced limited early fusions at 6 months (22.7%) yet improved at 1 year (71.4%). OsteoAMP® facilitated fusion for the majority of patients by 6 months (54.1%) and nearly all patients within 1 year (93.9%). At 18 months, 99.3% of OsteoAMP® patients had fused while the rhBMP-2 arm had an 86.7% fusion rate. Total time for fusion for OsteoAMP® was approximately half that of rhBMP-2 at 211.4 days and 407.1 days respectively. A subset cohort of 47 patients in the rhBMP-2 arm had OsteoAMP® packed anterior to the PEEK cage. When OsteoAMP® was used as an extender to rhBMP-2 in this manner, fusion rates increased at all timepoints (p=0.05 at 18 months) over patients that only had rhBMP-2 and local bone within the disc space. Though, the fusion rates of OsteoAMP® without rhBMP-2 remained higher than the rhBMP-2/local bone/OsteoAMP® extender cohort at all timepoints (p<0.05). To further isolate the effect of OsteoAMP, a subset cohort of 52 patients within the OsteoAMP® treatment arm in the absence of rhBMP-2 did not utilise bone marrow aspirate. The fusion rates of patients within this cohort was statistically higher at 6 months but did not show statistically higher fusion rates at 3 months, 12 months, or 18 months (p>0.12). When compared to the rhBMP-2 study arm, patients within the OsteoAMP® arm that did not receive bone marrow aspirate demonstrated higher fusion rates at all time points (p<0.04 at 12 and 18 months). The rhBMP-2 arm had more than 5 times the incidence of radiologically evident adverse events (osteolysis and ectopic bone formation) compared to the OsteoAMP® arm (43.3% vs. 8.2%, respectively). Discussion. Despite its use with an older patient population and a higher number of levels per surgery, OsteoAMP® has shown great promise as a faster and safer alternative to rhBMP-2 in lumbar spine surgery

Summary. 45S5 bioactive glass combined with hMSC did not permit de novo ectopic bone formation. Such absence of osteogenicity was most likely due to the alkalinization of the 45S5 microenvironment that affects adversely the osteogenic differentiation of stem/precursor cells. Bone marrow stromal cells (BMSCs) are capable of bone formation and can promote the repair of osseous defects when implanted in appropriate scaffolds. The most promising biomaterials for application in bone tissue engineering (TE) are hydroxyapatite (HA), tricalcium phosphate (TCP), calcium carbonate (coral) ceramics or bioactive glasses (BG) because of their osteoconductive properties and ability to enhance bone formation. However, information regarding the osteogenic potential of hBMSCs in combination with BG scaffolds is strikingly lacking in the TE field. The present study focused on evaluating the osteogenicity of bone constructs prepared from particles of 45S5 BG combined with hBMSCs in comparison with biphasic HA/TCP or coral particles, in a mouse ectopic model. The in vivo osteogenicity was then correlated with various aspects of the effects of the scaffold materials tested on hBMSCs functions pertinent to bone tissue formation. Particular attention was given to the pH in the microenvironment where the cells reside in TE constructs and its effect on the osteoblastic differentiation of hBMSCs. In vivo experiments evidenced that 45S5 BG constructs with hBMSCs failed to form ectopic bone. In contrast, the cell constructs prepared with either HA/TCP or coral ceramics displayed great and consistent capacity for the ectopic bone formation. The cytocompatibility of hBMSCs on BG material was addressed and no differences were evidenced between HA/TCP and coral substrates related to the adhesion of hBMSCs and their proliferation in vitro. The hBMSCs viability was even higher within the 45S5 BG-containing constructs compared to the other two types of material constructs tested both in vitro and in vivo. These findings indicated that the absence of de novo bone formation in the hBMSCs-containing 45S5 BG constructs was not the result of cytotoxic effects of the BG material. The potential of osteogenic differentiation of hBMSCs cultured on material substrates was next addressed and the ALP activity of hBMSCs was significantly diminished when these cells were cultured on 45S5 BG as compared to either HA/TCP or coral substrates. Because BG materials are well-known for causing external alkalinisation, the pH was specifically measured in TE constructs. The pH inside the cell-containing BG constructs, measured ex vivo, was 8.0 (i.e. 0.4–0.5 units more alkaline than that measured in the coral- or HA/TCP-constructs). The impact of such external alkalinisation on the osteogenic differentiation of hBMSCs was assessed by culturing the cells over a wide range of alkaline pH. The hBMSCs expression of osteogenic markers, ALP activity and mineralization were not significantly affected at moderate external alkaline pH (≤ 7.90) but were dramatically inhibited at higher pH. Altogether, these findings provided evidence that despite 45S5 BG are reported to be good osteoconductive materials, they are not necessarily good scaffolds for TE, most likely due to the alkalinization of the 45S5 microenvironment that affects adversely the osteogenic differentiation of precursor cells. Controlling the shifts of pH in the local engineered extracellular environment is a critical issue for the development of bioactive TE scaffolds

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

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.

A Ruys, School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney. The effects of bone anabolics can be maximised by systemic co-treatment with an anti-catabolic. Local treatment may reduce the total drug required and produce superior outcomes, although high dose local bisphosphonate has been reported to impair bone formation. We have explored local co-delivery of anabolic/anti- catabolic bone drugs at different doses. We manufactured biodegradable poly-D,L-lactic acid (PDLLA) polymer pellets containing 25g BMP-7 as an anabolic with or without 0.002mg-2mg Pamidronate (PAM) as an anti-catabolic. Polymer pellets were surgically implanted into the hind limb muscle of female C57BL6 mice. Animals were sacrificed at three weeks post- implantation and bone formation was assessed by radiography, microcomputed tomography (microCT) and histology. Histological staining on five Âm paraffin sections included haematoxylin/eosin, alcian blue/picrosirius red, and tartrate- resistant acid phosphatase (TRAP). Radiographic and microCT data confirmed that 0.02mg and 0.2mg local PAM doses significantly augmented BMP-7 induced bone formation. In contrast, 2mg local PAM dramatically reduced the amount of bone present. This dose was comparable to that used by Choi et al who also reported impaired bone formation in a skull defect model.2 three-dimensional microCT and histological analyses of the ectopic bone and surrounding muscle showed a cortical shell covering the polymer pellet, which had not completely resorbed. Histological analysis at the pellet/bone interface showed tissue granulation and no inflammation, suggesting a high biocompatibility of the PDLLA polymer. The presence of bisphosphonate also decreased the amount of fatty marrow tissue seen within between the cortical shell and the unresorbed polymer. For the first time we can demonstrate synergy with local BMP/bisphosphonate. This study confirms that high local PAM doses can have negative effects, indicating a need to avoid overdosing. The lack of implant degradation suggests a need to optimise polymer degradation for bone tissue engineering application