We immobilised the right hindlimbs of six-month-old female Wistar rats for four weeks using a biplanar external fixation bridging the knee. The untreated left limbs served as a control group. An additional group of rats was allowed to recover for four weeks after removal of the frame. Immobilisation caused reduction in the wet weights of approximately 50% in the gastrocnemius, quadriceps, soleus and plantaris muscles; this was not restored completely after remobilisation. There was an increase in the activity of acid phosphatase of approximately 85% in the gastrocnemius and quadriceps muscles whereas that of creatine phosphokinase was reduced by about 40%. These values returned to nearly normal after remobilisation. Histological and ultrastructural examination showed a marked myopathy of the gastrocnemius muscle after immobilisation although the morphology was largely restored after remobilisation. We conclude that after four weeks of remobilisation, hind-limb muscles do not return to preimmobilisation weights, although biochemical activities and ultrastructural appearance are largely restored

We studied the sensory afferent properties of normal, immobilised and inflamed rat knees by recording the activity of the medial articular nerve (MAN). When the knee was inflamed by kaolin-carrageenan or immobilised for six weeks, MAN activity significantly increased during rest and continuous passive motion (CPM). The maximal discharge rate tended to increase depending on the angular velocity of the CPM. When the knees were then rested for one hour before again starting CPM, activity was further increased at the initial CPM cycle, the ‘post-rest effect’. Analysis of the conduction velocity showed that 94% and 66% of spike units on the recorded discharge of the immobilised and inflamed knees, respectively, belonged to fine nerve fibres. Our findings show that the sensory receptors in the knee are sensitised in a similar manner by immobilisation and by inflammation, suggesting a relationship to pain. The post-rest effect may be related to a characteristic symptom of osteoarthritis called ‘starting pain’

Total shoulder arthroplasty (TSA) and Reverse Total shoulder arthroplasty (RSA) are two of the most performed shoulder operations today. Traditionally postoperative rehabilitation included a period of immobilisation, protecting the joint and allowing time for soft tissue healing. This immobilisation period may significantly impact a patient's quality of life (Qol)and ability to perform activities of daily living (ADL's). This period of immobilisation could be safely avoided, accelerating return to function and improving postoperative QoL. This systematic review examines the safety of early mobilisation compared to immobilisation after shoulder arthroplasty focusing on outcomes at one year. Methods. A systematic review was performed as per the PRISMA guidelines. Results on functional outcome and shoulder range of motion were retrieved. Six studies were eligible for inclusion, resulting in 719 patients, with arthroplasty performed on 762 shoulders, with information on mobilisation protocols on 736 shoulders (96.6%) and 717 patients (99.7%). The patient cohort comprised 250 males (34.9%) and 467 females (65.1%). Of the patients that successfully completed follow-up, 81.5% underwent RSA (n = 600), and 18.4% underwent TSA (n = 136). Overall, 262 (35.6%) patients underwent early postoperative mobilisation, and 474 shoulders were (64.4%) immobilised for a length of time. Immobilised patients were divided into three subgroups based on the period of immobilisation: three, four, or six weeks. There were 201 shoulders (27.3%) immobilised for three weeks, 77 (10.5%) for four weeks and 196 (26.6%) for six weeks. Five of the six manuscripts found no difference between clinical outcomes at one year when comparing early active motion versus immobilisation after RSA or TSA. Early mobilisation is a safe postoperative rehabilitation pathway following both TSA and RSA. This may lead to an accelerated return to function and improved quality of life in the postoperative period

Introduction and Objective. Scaphoid waist fractures (SWF) are notable in upper limb trauma and predominantly occur in young men. Morbidities associated with SWF include fracture non-union, premature arthritis and humpback deformity. Delayed treatment and non-adherence to fracture immobilisation increases likelihood of these complications. There is evidence that men engage in negative health behaviours such as delayed help-seeking. The Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) conducted interviews in individuals who had sustained a SWF. Although SWIFFT showed multiple social determinants for the overall injury and healing experience, a key factor this novel study considers is age and sex. This study aimed to analyse interview data from young male participants in SWIFFT to help distinguish the experience of SWF in young men, through exploring the influence of masculinity. Materials and Methods. A purposive sample of 12 young male participants were selected from SWIFFT. These participants were enrolled from a possibility of 13 different centres across Britain. There were 17 semi-structured interviews produced from these participants, and this was thought to be sufficient for data saturation. These interviews were evaluated through deductive thematic analysis with an open-coding approach, with respondents’ experiences being compared against themes documented in men's health literature. The “Braun and Clarke (2006) Six Phases of Thematic Analysis” methodology was adopted to perform this. Results. There were three thematic models developed in the data set, which then were further divided into subthemes. Model 1: Negative Health Behaviour Prior to Treatment, model 2: Feeling Frail and model 3: Need for Speed. Model 1 corroborated that participants were inclined to sustain the injury as a result of risk-taking and would subsequently hesitate to seek treatment. Model 2 indicated that as a result of the injury, respondents were unable to engage in physical activities and activities of daily living. Respondents exercised caution to varying extents after sustaining a SWF. Model 3 highlighted that interviewees were prone to non-adherence with fracture immobilisation and in hindsight resumed employment prematurely. Conclusions. The findings of this study demonstrate that masculinity is significantly influential on the experience of SWF in young men. This was indicated through the results of thematic analysis strongly corresponding with behaviours established in men's health literature. Educational interventions could be of value in addressing behaviours observed in this population group, such as delayed help-seeking and non-compliance with fracture immobilisation. Further work in patient education and concordance with treatment after sustaining a SWF may be beneficial to longer term outcomes. In turn, this may reduce complications associated with SWF in young men

Introduction and Objective. Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. Materials and Methods. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus non-weight-bearing (NWB) and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures (lateral malleolar, bimalleolar, trimalleolar with or without syndesmotic injury). The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection (deep and superficial), displacement of osteosynthesis, the full arc of ankle motion (plantar flexion and dorsal flection), RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay. Results. We recruited 160 patients with an unstable ankle fracture. Participants’ ages ranged from 15 to 94 years (M = 45.5, SD = 17.2), with 54% identified as female. The mean time from injury to surgical fixation was 1.3 days (0 to 17 days). Patients in the immediate weight-bearing group had a 9.5-point higher mean OMAS at six weeks postoperatively (95% CI 1.48, 17.52) P = 0.021. The complications rate was similar in both groups. The rate of surgical site infection was 4.3%. One patient had DVT, and another patient had a pulmonary embolism; both were randomised to NWB. Length of hospital stay (LOS) was 1 ± 1.5 (0, 12) for the IWB group vs 1.5 ± 2.5 (0, 19) for the NWB group. Conclusions. There is a paucity of quality evidence supporting the postoperative management regimes used most commonly in clinical practice. To our knowledge, immediate weight-bearing (IWB) following ORIF of all types of unstable ankle fractures has not been investigated in a controlled prospective manner in recent decades. In this large multicentre, randomised controlled trial, we investigated immediate weight-bearing following ORIF of all ankle fracture patterns in the usual care condition using standard fixation methods. Our result suggests that IWB following ankle fracture fixation is safe and resulted in a better functional outcome. Once anatomical reduction and stable internal fixation is achieved, we recommend IWB in all types of ankle fractures in a compliant patient

Is Non-Weight-Bearing Necessary? (INWN) is a pragmatic multicentre randomised controlled trial comparing immediate protected weight-bearing (IWB) with non-weight-bearing cast immobilisation (NWB) following ankle fracture fixation (ORIF). This trial compares; functional outcomes, complication rates and performs an economic analysis to estimate cost-utility. IWB within 24hrs was compared to NWB, following ORIF of all types of unstable ankle fractures. Skeletally immature patients and tibial plafond fractures were excluded. Functional outcomes were assessed by the Olerud-Molander Ankle Score (OMAS) and RAND-36 Item Short Form Survey (SF-36) taken at regular follow-up intervals up to one year. A cost-utility analysis via decision tree modelling was performed to derive an incremental cost effectiveness ratio (ICER). A standard gamble health state valuation model utilising SF-36 scores was used to calculate Quality Adjusted Life Years (QALYs) for each arm. We recruited 160 patients (80 per arm), aged 15 to 94 years (M = 45.5), 54% female. Complication rates were similar in both groups. IWB demonstrated a consistently higher OMAS score, with significant values at 6 weeks (MD=10.4, p=0.005) and 3 months (MD 12.0, p=0.003). Standard gamble utility values demonstrated consistently higher values (a score of 1 equals perfect health) with IWB, significant at 3 months (Ẋ = 0.75 [IWB] / 0.69 [NWB], p=0.018). Cost-utility analysis demonstrated NWB is €798.02 more expensive and results in 0.04 fewer QALYs over 1 year. This results in an ICER of −€21,682.42/QALY. This negative ICER indicates cost savings of €21,682.42 for every QALY (25 patients = 1 QALY gain) gained implementing an IWB regime. IWB demonstrates a superior functional outcome, greater cost savings and similar complication rates, compared to NWB following ankle fracture fixation

Introduction and Objective. Postoperative management regimes vary following open reduction and internal fixation of unstable ankle fractures. There is an evolving understanding that poorer outcomes could be associated with non-weight bearing protocols and immobilisation. Traditional non-weight bearing cast immobilisation may prevent loss of fixation, and this practice continues in many centres. The aim of this systematic review and meta-analysis is to compare the complication rate and functional outcomes of early weight-bearing (EWB) versus late weight-bearing (LWB) following open reduction and internal fixation of ankle fractures. Materials and Methods. We performed a systematic review with a meta-analysis of controlled trials and comparative cohort studies. MEDLINE (via PubMed), Embase and the Cochrane Library electronic databases were searched inclusive of all date up to the search time. We included all studies that investigated the effect of weight-bearing following adults ankle fracture fixation by any means. All ankle fracture types, including isolated lateral malleolus fractures, isolated medial malleolus fractures, bi-malleolar fractures, tri-malleolar fractures and Syndesmosis injuries, were included. All weight-bearing protocols were considered in this review, i.e. immediate weight-bearing (IMW) within 24 hours of surgery, early weight-bearing (EWB) within three weeks of surgery, non-weight-bearing for 4 to 6 weeks from the surgery date (or late weight-bearing LWB). Studies that investigated mobilisation but not weight-bearing, non-English language publications and tibial Plafond fractures were excluded from this systematic review. We assessed the risk of bias using ROB 2 tools for randomised controlled trials and ROBINS-1 for cohort studies. Data extraction was performed using Covidence online software and meta-analysis by using RevMan 5.3. Results. After full-text review, fourteen studies (871 patients with a mean age ranged from 35 to 57 years) were deemed eligible for this systematic review; ten randomised controlled trials and four comparative cohort studies. Most of the included studies were rated as having some concern with regard to the risk of bias. There is no important difference in the infection rate between protected EWB and LWB groups (696 patients in 12 studies). The risk ratio (RR) is 1.30, [95% CI 0.74 to 2.30], I. 2. = 0%, P = 0.36). Other complications were rare. The Olerud-Molander Ankle Score (OMAS) was the widely used patient-reported outcome measure after ankle fracture fixation among the studies. The result of the six weeks OMAS analysis (three RCTs) was markedly in favour of the early weight-bearing group (MD = 10.08 [95% CI 5.13 to 15.02], I. 2. = 0%P = <0.0001). Conclusions. The risk of postoperative complications is an essential factor when considering EWB. We found that the overall incidence of surgical site infection was 6%. When comparing the two groups, the incidence was 5.2% and 6.8% for the LWB and EWB groups. This difference is not clinically important. On the other hand, significantly better early functional outcome scores were detected in the EWB group. These results are not without limitations. Protected early weight-bearing following open reduction and internal fixation of ankle fractures is potentially safe and improve short-term functional outcome. Further good-quality randomised controlled trials would be needed before we could draw a more precise conclusion

Abstract. Objectives. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. Methods. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus NWB and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures. The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection, displacement of osteosynthesis, the full arc of ankle motion, RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay. Results. We recruited 160 patients with an unstable ankle fracture. Participants’ ages ranged from 15 to 94 years (M = 45.5, SD = 17.2), with 54% identified as female. The mean time from injury to surgical fixation was 1.3 days (0 to 17 days). Patients in the IWB group had a 9.5-point higher mean OMAS at six weeks postoperatively (95% CI 1.48, 17.52) P = 0.021 with a similar result at three months. The complications rate was similar in both groups. The rate of surgical site infection was 4.3%. One patient had DVT, and another patient had a PE, both were randomised to NWB. Length of hospital stay was 1 ± 1.5 (0, 12) for the IWB group vs 1.5 ± 2.5 (0, 19) for the NWB group. Conclusion. In this large multicentre RCT, we investigated WB following ORIF of all ankle fracture patterns in the usual care condition using standard fixation methods. Our result suggests that IWB following ankle fracture fixation is safe and resulted in a better functional outcome

Background. Avulsion fractures of the base of the fifth metatarsal are some of the commonest foot injuries. The robust scientific evidence on the optimal non-operative treatment of these fractures is scant. We designed and conducted a prospective randomised non-inferiority controlled trial of symptomatic treatment versus cast immobilisation with the null hypothesis that cast immobilisation gave substantial benefit over the symptomatic treatment in terms of patient reported outcome measures(PROMs). The alternative hypothesis was that symptomatic treatment was not inferior. Methods. The primary outcome was the validated Visual Analogue Scale Foot and Ankle (VAS FA) score ranging from 0 to 100. The non-inferiority boundary was set at −10 points. Power sizing determined a minimum of 12 patients per group. Anticipating a significant loss to follow up, 60 patients of 16 years of age or older were randomised to receive either below knee walking cast immobilisation (n = 24) or symptomatic double- elasticated bandage (n = 36) for 4 weeks. Secondary outcome measures were EuroQol-5D, and American Orthopaedic Foot and Ankle Society scores. Data was analysed at the baseline, 4 weeks, 3 months and 6 months post injury by a clinician blinded to a treatment arm. Results. Symptomatic treatment proved to be non-inferior to cast immobilisation treatment in terms of VAS FA at baseline, 4 weeks and 6 months. Secondary outcomes showed similar comparative values between two treatment groups. Loss to follow up reached 43% at 6 months. The imputation of missing data was done and confirmed the non-inferiority of symptomatic treatment. Conclusions. Cast immobilisation does not appear to give benefits over symptomatic treatment of these injuries in terms of validated PROMs in adults. A significant loss to follow up should be expected with these fractures in medium term. Level of Evidence. II. Approval. NRES Yorkshire and the Humber reference: 11/YH/0297. Disclosure. This study was supported with a small research grant from a British Orthopaedic Foot and Ankle Society

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods. In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days. Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response

Despite widespread use of radiofrequency (RF) shrinkage, there have been no animal studies on the effects of post-operative immobilisation on the histological properties of the shrunken tissue. We have therefore examined the role of post-operative immobilisation after RF shrinkage with special emphasis on the histological properties of collagenous tissue. One patellar tendon of 66 New Zealand White rabbits was shrunk. Six rabbits were killed immediately after the operation. Twenty rabbits were not immobilised, 20 were immobilised for three weeks and 20 for six weeks. Fibroblasts, collagen and vascular quality and density were evaluated on sections, stained by haematoxylin and eosin. Nine weeks after operation the histological properties were inferior to those of the contralateral control tendons. Shrunk tendons did not return to normal at any time after operation irrespective of whether the animals had been immobilised or not. All the parameters improved significantly between zero and three weeks after operation. Immobilised tendons tended to have a better and faster recovery. Careful rehabilitation is imperative after RF shrinkage. Immobilisation aids recovery of the histological properties. Our findings in this animal model support a period of immobilisation of more than three weeks

Developmental dysplasia of the hip (DDH) is the most common post-natal skeletal abnormality. It is widely acknowledged that conditions which cause or result in reduced movement in utero are contributing factors to the incidence of DDH. However, the hypothesis that prenatal movement plays a role in normal development of the hip joint has not been tested using embryonic model systems. This research investigates the effects of immobilization in chick embryos on hip joint morphogenesis. Embryonic chicks were treated in ovo using a neuromuscular blocking agent from embryonic days 5 to 9. Limbs were stained for cartilage using alcian blue, and were scanned in 3-D. Standardized virtual sections of the femur were taken and a number of virtual sections from age-matched limbs were overlaid in order to compare between control and immobilized limbs. The results show that not all immobilised limbs were equally affected, with some immobilised embryos having almost normal joint shapes, and other immobilised embryos displaying decreased protuberance of the femoral head and decreased indentation at the femoral neck. Our results demonstrate that the mechanobiological response to immobilisation can vary between individuals, but also that preventing movement during embryonic development can lead to abnormal morphogenesis of the developing proximal femur in some individuals, providing evidence that reduced movement during development can lead to features of DDH

Lower limb fractures are commonly treated with cast immobilization, and as a main consequence of strict immobilization this typically leads to loss in muscle mass, decrease of bone density and decline in functional abilities. Body-worn sensors are increasingly used to assess outcome in clinical trials by providing objective mobility parameters in a real-world environment. The aim of this study is to investigate the usability aspects and potential changes in mobility parameters in partial-immobilization patients in real-world conditions. Six healthy young males (age 22.2 ± 1.2 years; weight 76.5 ± 6.7 kg, height 185.8 ± 6.1 cm. Mean ± standard deviation) wore a leg cylinder cast with walker boot to immobilize their dominant leg for two consecutive weeks. Subjects were asked to continuously wear a tri-axial accelerometer on the waist (actibelt) during waking hours for 6 weeks including 2 weeks before, during and after cast immobilisation. The total amount of days of continuous recording was 339 days with a total wearing time of 120 days. Software packages which allow to detect steps and to estimate real-world walking speed were used to analyse the accelerometry data. It was suspected that knee immobilization would affect strongly the wave form of the signal with an impact on the accuracy of the speed algorithm, whereas the step detection should be more robust. This effect was confirmed in a preliminary study performed to quantify the accuracy under immobilization conditions. On the other hand, step numbers are known to be sensitive to fluctuations in wearing time which was not uniform throughout the entire study. We concluded that in this setting step frequency is the most reliable parameter. Step frequency showed a systematic decrease in the values during the immobilization period which recovered to pre-immobilisation values after cast removal. This confirms the usability of accelerometry and sensitivity of its mobility parameters for clinical outcome assessment

Summary. These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation and therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans. Introduction. Stimulation of bone formation by PTH is known to, in part, act via increased mechanosensitivity. Therefore, unloading should decrease the response to PTH treatment in uninjured bone. This has served as a background for speculations that PTH might be less efficacious for human fracture treatment in unloaded limbs, e.g. for distal radial fractures. We analyzed if the connection with mechanical stimulation also pertains to bone formation after trauma in cancellous bone. Methods. 20 male SD rats, 8 weeks old, had one hind leg immobilised via Botox injections. At 10 weeks of age the rats received bilateral screw implants into their proximal tibiae. Half of the rats were given daily injections of 5µg/kg PTH(1–34). After two weeks of healing, the tibias and femurs were harvested. Mechanical testing of screw fixation (pull-out) and µCT of the cancellous bone of the distal femurs was performed. Results. The pull-out forces served as a read-out for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded (from 30 to 44 N). These force values are not limited by a ceiling effect, and the difference in relative effect of PTH was significant (p = 0.03). Discussion/Conclusion. PTH appeared to exert a greater effect on bone healing in the unloaded limbs, compensating for the lack of mechanical stimulation. These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation. Therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans

Frictional resistance to tendon gliding is minimised by surrounding loose areolar tissues. During periods of prolonged immobilisation, for example post tendon-repair, adhesions can form between the two adjacent tissues, thereby limiting function. Whilst agents applied during surgery are recognised to succeed in adhesion prevention, they have also been reported to provide some reduction in friction during in vitro tendon-bony pulley investigations. This study investigated the effectiveness of common anti-adhesion agents in lubricating the tendon-surrounding tissue contact by comparison with a control study. By using a validated apparatus and with reference to the Stribeck curve, it was determined that the natural in vivo contact is likely to be lubricated by a film of synovial-like fluid. Application of all anti-adhesives generated a similarly efficient lubricating system, and hence administration of these agents should be encouraged to all regions of the tendon disrupted during surgery. Minimising frictional resistance to gliding will reduce the likelihood of tendon ‘gapping’ - and subsequently failure - at the repair site

Controlled differentiation of Human mesenchymal stem cells (hMSCs) is required for timely induction of bone growth in implantable biomaterials. Differentiation of hMSCs towards a particular lineage depends upon their microenvironment, which is a complex mixture of various physical, chemical and biological parameters. The role of Bone morphogenic protein (BMP2) in early induction of bone formation is well established. Clinical experience and in vitro study has shown that presentation of this protein in small quantities by surface immobilisation significantly induces osteogenic differentiation compared to large quantities provided in solution. This project focuses on developing and understanding responsive micro/nano porous interfaces which deliver BMP2 in a dose dependent fashion to control osteogenic diffentiation of hMSCs. We hypothesise that use of porous membranes primed with LbL deposition of biomacromolecules such as COL and HA will help in induction of cell attachment and growth whilst controlled and localised delivery of BMP2 released from the layers of these porous constructs will induce sustained differentiation of hMSCs. By controlling pore size of membranes, rate of release of BMP2 can be controlled. We use fluorescently labelled Dextran (Flu-DEX) as model protein to study control release mechanism, which is of similar size to BMP2. Polycarbonate (PC) track etched membranes with various pore sizes were used for LbL assembly of COL/HA/Flu-DEX along with hydrolytically degradable polymer Poly-Beta amino ester (Poly2). Six bilayers were constructed into porous membranes with (COL-Flu-DEX)6 and (Poly2-Flu-DEX)6. Use of hydrolytically degradable polymer significantly enhances release of Flu-DEX compared to control (COL-Flu-DEX)6 assembly. Compared to flat (non porous) surface, release from porous samples maintained a relatively slow and steady release. We are currently investigating release of BMP2 using this approach and their influence on the differentiation of hMSCs in vitro

Summary Statement. A resorbable and biocompatible polymer-based scaffold was used for the proliferation and delivery of adipose derived stromal cells, as well as delivery of a cell growth/differentiation promoting factor for improved tendon defect regeneration. Introduction. Surgeons perform thousands of direct tendon repairs annually. Repaired tendons fail to return to normal function following injury, and thus require continued efforts to improve patient outcomes. The ability to produce regenerate tendon tissue with properties equal to pre-injured tendon could lead to improved treatment outcomes. The aim of this study was to investigate in vivo tendon regeneration using a biodegradable polymer for the delivery of adipose derived stromal cells (ADSCs) and a polypeptide, growth/differentiation factor-5/(GDF-5), in a tendon gap model. Patients & Methods. Female Fischer 344 rats underwent unilateral Achilles tenotomies. Defects were left un-repaired (Group 1-control), bridged using electrospun 65:35 polylactide-co-glycolide (PLAGA) tubular scaffolds (Group 2), PLAGA/ADSCs (Group 3), or PLAGA/GDF-5 (Group 4) scaffold composites. The plantaris was left intact. Operative limbs were immobilised for 10–14 days, followed by unrestricted activity. The rats were sacrificed at 4 weeks or 8 weeks after surgery, and tendons were assessed with histological, biochemical, and mechanical analyses. Results. PLAGA, PLAGA/ADSCs, and PLAGA/GDF-5 groups showed increased collagen I gene expression at both the 4 and 8 week time points (p<0.05). Tenomodulin (Tnmd) is the mature tendon phenotype marker unique to tendon tissue. Both the PLAGA/ADSCs and PLAGA/GDF-5 groups demonstrated increased tenomodulin expression at 4 and 8 weeks (p<0.05). Ultimate tensile load strength was improved in all PLAGA groups (2, 3, and 4) versus the control. Both composite groups (2 and 3) showed improved collagen deposition, as indicated by increased Collagen Area Fraction (CAF), approaching that of normal tendon at 8 weeks (p<0.05). Scaffold resorption was evident at 4 weeks, with complete replacement of the polymer with regenerate tissue and minimal gap formation at 8 weeks without evidence of an adverse inflammatory reaction. Defects bridged using the scaffold seeded with ADSCs showed improved collagen organization and increased modulus of elasticity compared with controls as well as properties approaching those of native tendon. Discussion/Conclusions. These results demonstrate that a tubular bioresorbable scaffold can promote extracellular matrix synthesis and organization, and the formation of neo-tendinous tissue; as well as serve as a carrier of adipose stromal cells and growth factors that are effective for tendon regeneration. Cells, growth factors and synthetic biomaterial polymers may be combined as a paradigm for regenerative engineering thereby serving as promising options for improved treatments of tendon injuries and potentially improving patient outcomes

Summary. Our results prove that Demineralised Cortical Bone (DCB) can be used as biological tendon graft substitute, combined with correct surgical technique and the use of suture bone anchor early mobilisation can be achieved. Introduction. Surgical repair of tendon injuries aims to restore length, mechanical strength and function. In severe injuries with loss of tendon substance a tendon graft or a substitute is usually used to restore functional length. This is usually associated with donor site morbidity, host tissue reactions and lack of remodelling of the synthetic substitutes which may result in suboptimal outcome. In this study we hypothesise that DCB present in biological tendon environment with early mobilisation and appropriate tension will result in remodelling of the DCB into ligament tissue rather that ossification of the DCB at traditional expected. Our preparatory cadaveric study (abstract submitted to CORS 2013) showed that the repair model used in this animal study has sufficient mechanical strength needed for this animal study. Methods. 6 mature female sheep undergone surgical resection of the distal 1 cm of the right patellar tendon and osteotomy of patellar tendon attachment at the tibial tuberosity under general anaesthesia. Repair was done using DCB with 2 suture bone anchor. Animals were allowed immediate mobilisation after surgery and were sacrificed at 12 weeks. The force passing through the operated and non-operated legs was assessed preoperatively and at week 3, week 6, week 9 and week 12 bay walking the animals over a force plate. Radiographs were taken immediately after euthanasia, the Patella-Tendon-tibia constructs were retrieved and pQCT scan was done. Histological analysis included tenocytes and chondrocytes cell counts, semi-quantitative scoring of the neo-enthesis and polarised microscopy. Result. In this study, none of the retrieved specimens showed any evidence of ossification of the DCB as proved by the pQCT analysis. One animal failed to show satisfactory progress after week 3, X-rays showed patella alta, on specimen retrieval no damage to the DCB was found, sutures and stitches were intact and no evidence of anchor pullout was found. Force plate analysis of the other 5 animals showed satisfactory progression over time with 44% functional weight bearing at week 3 progressing to 79% at week 12. There was full range of movement of the stifle joint after 12 weeks. Histological analysis proved formation of neo-enthesis with evidence of cellulisation, vascularisation and remodelling of the collagen leading to ligamentisation of the DCB. Discussion. Surgical reconstruction of damaged tendons is technically challenging, patellar tendon injuries presents even more challenging situation as it involves weight bearing joint. It is generally accepted that a period of immobilisation with passive range of movement exercises and protected weight bearing for up to 6 weeks post operatively is usually advised. Some surgeons use offloading metal wire to protect the repair for 6 weeks involving second surgical procedure to remove the wire. Demineralised bone is usually used in orthopaedics to utilise its osteogenic properties as bone graft substitute and to enhance osteogenesis in load bearing situations. In our study we explored a potential new use of the demineralised bone as tendon graft substitute, it acts as collagen scaffold allowing host cells to remodel its fibres into ligament like structure