14 research outputs found
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Genicular artery embolisation in patients with osteoarthritis of the knee (GENESIS 2): protocol for a double-blind randomised sham-controlled trial
Knee osteoarthritis is a leading cause of chronic disability and economic burden. In many patients who are not surgical candidates, existing treatment options are insufficient. Clinical evidence for a new treatment approach, genicular artery embolisation (GAE), is currently limited to single arm cohort, or small population randomised studies. This trial will investigate the use of a permanent embolic agent for embolisation of abnormal genicular arterial vasculature to reduce pain in patients with mild to moderate knee osteoarthritis. Up to 110 participants, 45 years or older, with knee pain forââ„â3 months resistant to conservative treatment will be randomised (1:1) to GAE or a sham procedure. The treatment group will receive embolisation using 100-micron Embozeneâą microspheres (Varian, a Siemens Healthineers Company) (investigational use for this indication in the UK), and the sham group will receive 0.9% saline in an otherwise identical procedure. Patients will be followed for 24 months. At 6 months, sham participants will be offered crossover to GAE. The primary endpoint is change of 4 Knee Injury and OA Outcome Score subscales (KOOS ) at 6 months post-randomisation. The study will also evaluate quality of life, health economics, imaging findings, and psychosocial pain outcomes. The primary manuscript will be submitted for publication after all participants complete 6 months of follow-up. The trial is expected to run for 3.5 years
The Health and Structural Consequences of Acute Knee Injuries Involving Rupture of the Anterior Cruciate Ligament
Novel approaches towards the successful implementation of tissue engineering strategies in impaction bone grafting
The scale-up of a tissue engineered porous hydroxyapatite polymer composite scaffold for use in bone repair: an ovine femoral condyle defect study
The development of an osteogenic bone graft substitute has important practical and cost implications in many branches of medicine where bone regeneration is required. Previous in vitro and small animal (murine) in vivo studies highlighted a porous hydroxyapatite/poly (dlâlactic acid) composite scaffold in combination with skeletal stem cells (SSCs) as a potential bone graft substitute candidate. The aim of the current study was to scale up the bone cellâscaffold construct to large animals and examine the potential for repair of a criticalâsized defect via an ovine model. SSC seeded scaffolds (and unseeded scaffold controls) were implanted bilaterally into ovine femoral condyle critical defects for 3 months. A parallel in vitro analysis of ovine SSC seeded scaffolds was also performed. Post mortem mechanical indentation testing showed the bone strengths of the defect sites were 20% (controls) and 11% (SSC seeded scaffolds) those of normal cancellous bone (pâ<â0.01). MicroCT analysis demonstrated new bone formation within all defects with a mean increase of 13.4% in the control scaffolds over the SSC seeded scaffolds (pâ=â0.14). Histological examination confirmed these findings, with enhanced quality new bone within the control defects. This study highlights important issues and steps to overcome in scaleâup and translation of tissue engineered products. The scaffold demonstrated encouraging results as an osteoconductive matrix; however, further work is required with cellular protocols before any human trials
Skeletal Regeneration: application of nanotopography and biomaterials for skeletal stem cell based bone repair
The application of selected skeletal progenitor cells and appropriate biomimetic microenvironments and nanotopographical surfaces offer the potential for innovative approaches to bone disease treatment and bone regeneration. Skeletal stem cells, commonly referred to as mesenchymal stem cells or human bone marrow stromal stem cells are multipotent progenitor cells with the ability to generate the stromal lineages of bone, cartilage, muscle, tendon, ligament and fat. This review will examine i) the application of innovative nanotopography surfaces that provide cues for human stem cell differentiation in the absence of chemical cues, ii) unique biomimetic microenvironments for skeletal tissue repair as well as iii) data from translational studies from the laboratory through to the clinic demonstrating the potential of skeletal cell based repair using impaction bone grafting as an exemplar. The development of protocols, tools and above all multidisciplinary approaches that integrate biomimetic materials, nanotopography, angiogenic, cell and clinical techniques for skeletal tissue regeneration for de novo tissue formation offers an opportunity to improve the quality of life of many
A tissue engineering strategy for the treatment of avascular necrosis of the femoral head
BACKGROUND & PURPOSE: Skeletal stem cells (SSCs) and impaction bone grafting (IBG) can be combined to produce a mechanically stable living bone composite. This novel strategy has been translated to the treatment of avascular necrosis of the femoral head. Surgical technique, clinical follow-up and retrieval analysis data of this translational case series is presented.METHODS: SSCs and milled allograft were impacted into necrotic bone in five femoral heads of four patients. Cell viability was confirmed by parallel in vitro culture of the cell-graft constructs. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone was retrieved from two retrieved femoral heads and was analysed by histology, microcomputed tomography (?CT) and mechanical testing.RESULTS: Three patients remain asymptomatic at 22- to 44-month follow-up. One patient (both hips) required total hip replacement due to widespread residual necrosis. Retrieved tissue engineered bone demonstrated a mature trabecular micro-architecture histologically and on ?CT. Bone density and axial compression strength were comparable to trabecular bone.CONCLUSIONS: Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head. Unique retrieval analysis of clinically translated tissue engineered bone has demonstrated regeneration of tissue that is both structurally and functionally analogous to normal trabecular bone
Skeletal tissue regeneration: current approaches, challenges, and novel reconstructive strategies for an aging population
Loss of skeletal tissue as a consequence of trauma, injury, or disease is a significant cause of morbidity with often wide-ranging socioeconomic impacts. Current approaches to replace or restore significant quantities of lost bone come with substantial limitations and inherent disadvantages that may in themselves cause further disability. In addition, the spontaneous repair capacity of articular cartilage is limited; thus, investigation into new cartilage replacement and regeneration techniques are warranted. Along with the challenges of an increasingly aging demographic, changing clinical scenarios and rising functional expectations provide the imperative for new, more reliable skeletal regeneration strategies. The science of tissue engineering has expanded dramatically in recent years, notably in orthopedic applications, and it is clear that new approaches for de novo skeletal tissue formation offer exciting opportunities to improve the quality of life for many, particularly in the face of increasing patient expectations. However, significant scientific, financial, industrial, and regulatory challenges should be overcome before the successful development of an emergent tissue engineering strategy can be realized. We outline current practice for replacement of lost skeletal tissue and the innovative approaches in tissue regeneration that have so far been translated to clinical use, along with a discussion of the significant hurdles that are presented in the process of translating research strategies to the clinic
Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies: translational issues
Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(lâlactic acid)âpoly(Δâcaprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrowâderived skeletal stem cells (SSCs) were implanted into midâshaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including microâCT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a criticalâsized defect compared to scaffold alone, using an external fixation construct, to bridge the scaleâup gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scaleâup this stem cell/binary blend polymer scaffold
Effects of setting bone cement on tissue-engineered bone graft: a potential barrier to clinical translation?
Background: Strategies to improve mechanical strength, neovascularization, and the regenerative capacity of allograft include both the addition of skeletal stemcells and the investigation of novel biomaterials to reduce and ultimately obviate the need for allograft altogether. Use of bone cement is a common method of stabilizing implants in conjunction with impacted allograft. Curing cement, however, can reach temperatures in excess of 70°C, which is potentially harmful to skeletal stem cells. The aim of this study was to investigate the effects of setting bone cement on the survival of human adult skeletal stem cells within tissue-engineered allograft and a novel allograft substitute.Methods: Milled allograft and a polymer graft substitute were seeded with skeletal stemcells, impacted into a graduated chamber, and exposed to curing bone cement. Sections were removed at 5-mm increments from the allograft-cement interface. A quantitative WST-1 assay was performed on each section as a measure of remaining cell viability. A second stage of the experiment involved assessment of methods to potentially enhance cell survival, including pretreating the allograft or polymer by either cooling to 5°C or coating with 1% Laponite, or both.Results: There was a significant drop in cellular activity in the sections taken from within 0.5 cm of the cement interface in both the allograft and the polymer (p < 0.05), although there was still measurable cellular activity. Pretreatment methods did not significantly improve cell survival in any group.Conclusions: While the addition of bone cement reduced cellular viability of tissue-engineered constructs, this reduction occurred only in close proximity to the cement and measurable numbers of skeletal stem cells were observed, confirming the potential for cell population recovery.Clinical Relevance: These studies highlight a potential pitfall when translating tissue-engineering strategies, but indicate that the use of bone cement should not necessarily be ruled out during the application of cell populations andbiomaterials in tissue regeneration