Syndesmotic fixation in Weber B ankle fractures: A systematic review.

Weber Type B fractures often arise from external rotation with the foot supinated or pronated. Altered tibiofibular joint kinematics in Weber B fractures are responsible for syndesmotic damage seen in Weber B fractures. Weber B fractures are managed using open reduction and internal fixation if displaced. The syndesmosis is injured in up to 40% of cases resulting in an unstable injury with a syndesmotic diastasis. This systematic review aimed to evaluate the current literature on syndesmotic fixation in Weber B fractures, assess the outcomes and complications of syndesmotic fixation and assess the necessity of syndesmotic fixation in Weber B fractures. A search was carried out on the EMBASE, PubMed and CINAHL databases and eight studies assessing the outcomes of syndesmotic fixations versus no syndesmotic fixation with 292 Weber B ankle fractures were included in this systematic review. Results showed significant heterogeneity so a narrative review was conducted. Results of these studies showed that functional, radiological, and quality-of-life outcomes and incidences of post-traumatic osteoarthritis in patients with syndesmotic screws were similar to those of patients not managed with syndesmotic screws. Only one favoured syndesmotic fixation in all cases of diastasis. As such, syndesmotic fixation with screws may not be necessary in the management of Weber B fractures. Screws are also associated with breakage, loosening, local irritation and infections. Suture button devices and antiglide fixation techniques appear to be valid alternatives to syndesmotic screws. It was found that there was no need for routine hardware removal unless the hardware was causing significant side effects for the patient.

Pronator quadratus repair after volar plating for distal radius fractures: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of the current study is to meta-analyze the randomized controlled trials in the literature comparing pronator quadratus repair versus no repair alongside volar plating of distal radius fractures. METHODS: A search of the PUBMED/MEDLINE, EMBASE, and The Cochrane Library databases was performed. Any randomized con- trolled trials comparing pronator quadratus repair versus no repair alongside volar plating of distal radius fractures were included. The relevant information was collected by 2 blinded reviewers using a predetermined data sheet. Clinical outcomes were compared, with all statistical analyses performed using Review Manager Version 5.3. RESULTS: Five randomized controlled trials with 273 patients were included. There was no significant difference in the range of motion in flexion-extension, ulnar-radial deviation, or pronation-supination. There was a significant difference in favor of the no repair group for Disabilities of the Arm, Shoulder and Hand (DASH) Score (MD [Mean Difference]: 2.63, P < .0001) and pronation strength (MD: 13, P < .0001). Furthermore, there was no significant difference in the visual analog scale score. There were 3 complications relating to pronator quadratus repair, in which patients developed carpal tunnel syndrome requiring a release. There was no significant difference in the re-operation rate. CONCLUSION: This study found that pronator quadratus repair when performing volar plating for distal radius fractures did not result in a significant improvement in functional outcome, range of motion, or strength. LEVEL OF EVIDENCE: I, Systematic Review of Level 1 Studies, Level I, Therapeutic Study.

Sarcopenia in Men With Bone-Predominant Metastatic Castration-Resistant Prostate Cancer Undergoing Ra-223 Therapy.

INTRODUCTION: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. METHODS: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated therefrom. Intrapatient musculoskeletal changes were analyzed across various time points. RESULTS: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). CONCLUSIONS: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.

Prx1+ MPCs Accumulate in the Dura Mater of Wild-Type and p21-/- Mice Followed by a Specific Reduction in p21-/- Dural MPCs.

Epidural fat contains a population of mesenchymal progenitor cells (MPCs), and this study explores the behavior of these cells on the adjacent dura mater during growth and in response to injury in a p21 knockout mouse model. p21-/- mice are known to have increased cell proliferation and enhanced tissue regeneration post-injury. Therefore, it is hypothesized that the process by which epidural fat MPCs maintain the dura mater can be accelerated in p21-/- mice. Using a Prx1 lineage tracing mouse model, the epidural fat MPCs are found to increase in the dura mater over time in both C57BL/6 (p21+/+ ) and p21-/- mice; however, by 3 weeks post-tamoxifen induction, few MPCs are observed in p21-/- mice. These endogenous MPCs also localize to dural injuries in both mouse strains, with MPCs in p21-/- mice demonstrating increased proliferation. When epidural fat MPCs derived from p21-/- mice are transplanted into dural injuries in C57BL/6 mice, these MPCs are found in the injury site. It is demonstrated that epidural fat MPCs play a role in dural tissue maintenance and are able to directly contribute to dural injury repair. This suggests that these MPCs have the potential to treat injuries and/or pathologies in tissues surrounding the spinal cord.

Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells.

Mesenchymal progenitor cells (MPCs) have been recently identified in human and murine epidural fat and have been hypothesized to contribute to the maintenance/repair/regeneration of the dura mater. MPCs can secrete proteoglycan 4 (PRG4/lubricin), and this protein can regulate tissue homeostasis through bio-lubrication and immunomodulatory functions. MPC lineage tracing reporter mice (Hic1) and human epidural fat MPCs were used to determine if PRG4 is expressed by these cells in vivo. PRG4 expression co-localized with Hic1+ MPCs in the dura throughout skeletal maturity and was localized adjacent to sites of dural injury. When Hic1+ MPCs were ablated, PRG4 expression was retained in the dura, yet when Prx1+ MPCs were ablated, PRG4 expression was completely lost. A number of cellular processes were impacted in human epidural fat MPCs treated with rhPRG4, and human MPCs contributed to the formation of epidural fat, and dura tissues were xenotransplanted into mouse dural injuries. We have shown that human and mouse MPCs in the epidural/dura microenvironment produce PRG4 and can contribute to dura homeostasis/repair/regeneration. Overall, these results suggest that these MPCs have biological significance within the dural microenvironment and that the role of PRG4 needs to be further elucidated.

Epidemiology of non-traumatic spinal cord injury in Ireland - a prospective population-based study.

Objective: To carry out a study of non-traumatic spinal cord injury (NTSCI) epidemiology in IrelandDesign: Prospective study of all new incident cases of NTSCI during 2017Setting: Republic of IrelandParticipants: All persons with a newly acquired NTSCIInterventions: NoneOutcome measures: Crude and age/sex specific incidences; ISCoS core dataset and non-traumatic dataset; population denominator was 2016 national census figures, adjusted to 2017.Results: Overall crude incidence of NTSCI in the Republic of Ireland in 2017 was 26.9 per million per year. Mean age at onset was 56.6 (SD 17.7) years. Females accounted for 51.2% of cases. Most frequent grade of ASIA impairment scale (AIS) was AIS D. Most common etiology was degenerate conditions (48.8%) followed by neoplastic (26.4%). The most common pattern of onset (51.2%) was lengthy (greater than one month).Conclusions: Incidence of NTSCI is more than double that for traumatic SCI in the Republic of Ireland. This suggests that the delivery of rehabilitation services to patients with spinal cord injuries requires prompt review and expansion.

The impact of the SARS-CoV-2 pandemic on referral characteristics in a national tertiary spinal injuries unit.

BACKGROUND: The SARS-CoV-2 pandemic has had profound implications on healthcare institutions. AIMS: This study aims to assess and compare referral patterns during COVID-19 to corresponding dates for the preceding 3 years (2017-2019), in order to preemptively coordinate the logistics of the surgical unit for similar future experiences. METHODS: Retrospective review for our institution, a national tertiary referral centre for spine pathology. Two distinct time-points were chosen to represent the varied levels of social restriction during the current pandemic: (i) study period 1 (SP1) from 11 November 2020 to 08 June 2020 represents a national lockdown, and (ii) study period 2 (SP2) from 09 June 2020 to 09 September 2020 indicates an easing of restrictions. Both periods were compared to corresponding dates (CP1: 11 March-08 June and CP2 09 June-09 September) for the preceding 3 years (2017-2019). Data collected included age, gender, and mechanism of injury (MOI) for descriptive analyses. MOIs were categorised into disc disease, cyclist, road-traffic-accident (RTA), falls < 2 m, falls > 2 m, malignancy, sporting injuries, and miscellaneous. RESULTS: All MOI categories witnessed a reduction in referral numbers during SP1: disc disease (-29%), cyclist (-5%), RTAs (-66%), falls < 2 m (-39%), falls > 2 m (-17%), malignancy (-33%), sporting injuries (-100%), and miscellaneous (-58%). Four of 8 categories (RTAs, falls < 2 m, malignancy, miscellaneous) showed a trend towards return of pre-lockdown values during SP2. Two categories (disc disease, falls > 2 m) showed a further reduction (-34%, -27%) during SP2. One category (sporting injuries) portrayed a complete return to normal values during SP2 while a notable increase in cyclist-related referrals was witnessed (+ 63%) when compared with corresponding dates of previous years. CONCLUSION: Spinal injury continues to occur across almost all categories, albeit at considerably reduced numbers. RTAs and falls remained the most common MOI. Awareness needs to be drawn to the reduction of malignancy-related referrals to dissuade people with such symptoms from avoiding presentation to hospital over periods of social restrictions.

Early fixation of traumatic spinal fractures and the reduction of complications in the absence of neurological injury: a retrospective cohort study from the American College of Surgeons Trauma Quality Improvement Program.

OBJECTIVE: The optimal timing of operative stabilization of patients with traumatic spinal fractures without spinal cord injury (SCI) has not been established. The challenges of early operative intervention, which may require prone positioning in a patient with multisystem injuries, must be balanced with the disadvantages of prolonged immobilization. The authors set out to define the optimal timing of surgical repair of traumatic spinal fractures in patients without SCI and the effect of delayed repair on the incidence of major complications. METHODS: A retrospective cohort study was conducted using data derived from the American College of Surgeons Trauma Quality Improvement Program. Adult trauma patients who underwent operative fixation of a spinal fracture within 7 days of admission were included. Patients with SCI were excluded. The primary outcome was the occurrence of a major complication. Secondary outcomes included death and length of stay. Restricted cubic splines were used to model the nonlinear effects of time to spinal fixation and determine a threshold beyond which stabilization was associated with a higher rate of major complications. Logistic regression and propensity score matching were then used to derive estimates for the association between delayed fixation and major complications. RESULTS: The authors identified 19,310 patients treated at 389 centers who met the inclusion criteria. Modeling identified fixation beyond 24 hours as a risk for major complications. Adjusting for potential confounders using multivariable logistic regression showed that late fixation was associated with a 1.30 (95% CI 1.15-1.46) times increased odds of developing a major complication. After propensity score matching, late fixation remained associated with a 1.25 (95% CI 1.13-1.39) times increased risk of experiencing a major complication. CONCLUSIONS: In the absence of clear contraindications, surgeons should strive to stabilize traumatic spinal fractures without SCI within 24 hours. Early fixation can be expected to reduce major complications by 25%-30%.

Sources, Identification, and Clinical Implications of Heterogeneity in Human Umbilical Cord Stem Cells.

Heterogeneity among different subpopulations of human umbilical cord mesenchymal stem cell (hUCMSCs) lines is an ubiquitous phenomenon, with such variability being related to several factors including the identity of the individual donor, tissue source (Wharton's jelly vs. umbilical cord blood), culture conditions, as well as random variations in the cloning expansion process. In this chapter, we provide a general overview on the sources as well as available experimental techniques for proper identification of heterogeneity in hUCMSCs. Finally, we provide a brief discussion on the current scientific evidence regarding the potential superiority of subpopulations of hUCMSCs for specific clinical applications. Taking into account the exponential growth on the available experimental data on hUCMSCs in the past few years, this chapter is not intended to be comprehensive in nature, but rather is intended to provide a general overview about the central role which the topic of heterogeneity has in both basic science and clinical research in umbilical cord stem cells.

Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat.

STUDY DESIGN: Isolation and characterization of human epidural fat (HEF) stem/progenitor cells. OBJECTIVE: To identify a progenitor population within HEF and to determine if they meet the minimal criteria of a mesenchymal stem cell (MSC). SUMMARY OF BACKGROUND DATA: The biological function, if any, has yet to be determined for HEF. The presence of MSCs within HEF may indicate a regenerative potential within the HEF. METHODS: HEF was isolated from 10 patients during elective spinal surgery. HEF cells were differentiated along osteo-, adipo-, and chondrogenic lineages, with differentiation analyzed via qPCR and histology. The cell surface receptor profile of HEF cells was examined by flow cytometry. HEF cells were also assayed through the collagen contraction assay. Prx1 CreERT2GFP:R26R TdTomato MSC lineage-tracking mice were employed to identify EF MSCs in vivo. RESULTS: HEF cell lines were obtained from all 10 patients in the study. Cells from 2/10 patients demonstrated full MSC potential, while cells from 6/10 patients demonstrated progenitor potential; 2/10 patients presented with cells that retained only adipogenic potential. HEF cells demonstrated MSC surface marker expression. All patient cell lines contracted collagen gels. A Prx1-positive population in mouse epidural fat that appeared to contribute to the dura of the spinal cord was observed in vivo. CONCLUSIONS: MSC and progenitor populations are present within HEF. MSCs were not identified in all patients examined in the current study. Furthermore, all patient lines demonstrated collagen contraction capacity, suggesting either a contaminating activated fibroblast population or HEF MSCs/progenitors also demonstrating a fibroblast-like phenotype. In vivo analysis suggests that these cell populations may contribute to the dura. Overall, these results suggest that cells within epidural fat may play a biological role within the local environment above providing a mechanical buffer.

Prospective epidemiological update on traumatic spinal cord injury in Ireland.

Study design: Prospective population-based epidemiological study on traumatic spinal cord injury in Ireland. Objectives: To provide updated data for the global TSCI repository. Setting: Republic of Ireland. Methods: All cases of TSCI acquired during 2016 were included. ISCoS core dataset was collected on all cases. Descriptive statistics are reported. Results: Overall crude incidence of TSCI was 12.8 per million (61 cases). Males accounted for 75.4%. Mean age at onset was 52.8 (19.9) years. Falls was the most common aetiology, 60.7% and AIS D was the most common injury level/AIS classification, 32.8%. The majority of patients (59%) were discharged home. Conclusions: Overall incidence of TSCI has changed very little since 2000 but many aspects of injury such as age and aetiologies are different. This data can now be included in the next TSCI global mapping update. Sponsorship: Health Research Board, Ireland.

Metastasis Affecting Craniocervical Junction: Current Concepts and an Update on Surgical Management.

STUDY DESIGN: Literature review. OBJECTIVES: Metastatic disease affecting the craniovertebral junction (CVJ) only accounts for 0.5% of all spine metastases. The management of these disease processes is complex, which involves multimodality radiological studies and various surgical approaches. We aimed to review the available evidence and summarize the findings in this review. METHODS: The authors conducted search of PubMed and Google Scholar with the following search terms: metastasis, craniovertebral junction (CVJ), occipitocervical, approaches, stability, and radiotherapy. Articles were reviewed by the authors and determined for inclusion based on relevance and level of evidence. RESULTS: The majority of relevant research reviewed composed of literature reviews of particular aspects regarding metastatic disease affecting the craniovertebral junction, including diagnosis, surgical approach, and radiotherapy. CONCLUSIONS: Prompt evaluation of rotational neck pain with or without occipital neuralgia may reveal early metastatic disease within a stable CVJ. Magnetic resonance imaging appears to be the gold standard imaging modality in detecting this pathology, with nuclear bone scan playing a role in distinguishing benign and malignant processes. Unfortunately, no level 1 evidence exists for use of either radiotherapy or surgery in these cases; however, from the available literature, spinal instability and evidence of progressive neurology are relative indications for operative intervention.

Epidemiology of Traumatic Spinal Cord Injury in Ireland, 2010-2015.

BACKGROUND: The International Spinal Cord Society and World Health Organisation recommend the collection of epidemiological data on traumatic spinal cord injury (TSCI). A 1-year prospective study is ongoing in Ireland. While the results of this study are awaited, it was concluded from a feasibility exercise that a complete retrospective dataset, 2010-2015, could be obtained and would be useful for service planning. METHODS: All patients with TSCI discharged from the national SCI acute and rehabilitation centres were included. Data was collected on gender, age, aetiology, level of injury, American Spinal Injuries Association impairment scale, length of rehabilitation admission and discharge destination. Population denominators were national census figures 2006 and 2011, rolled forward. RESULTS: The incidence of TSCI remained constant throughout the study period, 11.5-13.3 per million per year. The mean age of injury onset was 48.9 (SD 19.8) years. Males accounted for 71.5%. The most common injury level/AIS was incomplete tetraplegia, accounting for 43.2% of all TSCI. Leading aetiology was falls, accounting for 53.3% of injuries. Patients with incomplete tetraplegia were older than those with all other injuries (p < 0.001). CONCLUSIONS: The epidemiological trends identified are similar to those prevalent elsewhere in the developed world. More incomplete tetraplegia among an older patient population necessitates a review of how acute care and rehabilitation services are delivered.

Anterior Versus Posterior Thoracic Discectomy: A Systematic Review.

STUDY DESIGN: Systematic literature review. OBJECTIVE: The aim of this study was to systematically review the current evidence in the literature on thoracic discectomies, to compare the clinical outcomes, and to determine whether there is evidence to support the use of either the anterior or posterior approach. SUMMARY OF BACKGROUND DATA: Thoracic disc herniations (TDHs) often present with myelopathy, radiculopathy, or a combination of both. The posterior approach for thoracic discectomy has been associated with a lower complication rate, but no systematic review exists comparing the clinical outcomes. METHODS: MEDLINE, EMBASE, and The Cochrane Library databases were searched in accordance with the PRISMA guidelines for studies performing an anterior or posterior thoracic discectomy. The methodological quality was assessed using the Methodological Index for Non-Randomized Studies checklist. The reported clinical outcomes were evaluated using risk ratio, with a P < 0.05 being considered statistically significant. RESULTS: Thirty-seven clinical studies with 1156 patients with 1300 TDHs were included in this review. There was no statistically significant difference in the total neurological improvement or neurological worsening using either an anterior approach or a posterior approach (P = 0.02812 and P = 0.5232, respectively). However, there was a statistically significant higher rate of total complications in the anterior approach (P = 0.0024). CONCLUSION: The anterior approach and posterior approach have been shown to be very similar in terms of neurological outcomes. Although the posterior approach was shown to have a lower rate of total complications, this was largely because of a decrease in minor respiratory complications seen in the anterior approach. The optimal approach may therefore be based on surgeon preference as well as patient factors, specifically cardiorespiratory with American Society of Anaesthesiologists grading. LEVEL OF EVIDENCE: 4.

Aperius interspinous device for degenerative lumbar spinal stenosis: a review.

With an aging population, degenerative lumbar spinal stenosis (DLSS) leading to neurogenic intermittent claudication (NIC) is a growing problem. For patients suffering from this condition, interspinous process distraction devices (IPDs) offer an effective and cheap alternative to conservative or decompressive surgery. Aperius is one such device that has been gaining popularity for its percutaneous insertion under local anesthetic, short operative time, and low risk of complications. The main objective of this review was to carry out a comprehensive search of the literature to evaluate the effectiveness and potential complications of Aperius. A database search, including PubMed, Clinical trials.gov, Cochrane (CENTRAL), MEDLINE, CINAHL, EMBASE, and Scopus, was carried out to identify relevant articles written in English reporting on complications with a minimum 12-month follow-up. The literature search resulted in six eligible studies; two nonrandomized comparative and four prospective case series were available. The analysis revealed that in total, 433 patients underwent treatment with Aperius, with all studies demonstrating an improvement in outcome measures. The average follow-up was 17 months with an overall complication rate of 10.62%. Overall, the quality of evidence is low, suggesting that currently, the evidence is not compelling and further prospective randomized trials including cost-effectiveness studies are required.

Novel microhydroxyapatite particles in a collagen scaffold: a bioactive bone void filler?

BACKGROUND: Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2. QUESTIONS/PURPOSES: Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2). METHODS: A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups. RESULTS: Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect. CONCLUSIONS: The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns. CLINICAL RELEVANCE: The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects.

Innovative collagen nano-hydroxyapatite scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone formation.

The ability of nano-hydroxyapatite (nHA) particles developed in-house to act as non-viral delivery vectors is assessed. These nHA particles are combined with collagen to yield bioactive, biodegradable collagen nano-hydroxyapatite (coll-nHA) scaffolds. Their ability to act as gene-activated matrices for BMP2 delivery is demonstrated with successful transfection of mesenchymal stem cells (MSCs) resulting in high calcium production.

The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.