The management of periprosthetic distal femur fractures is an issue of increasing importance for orthopaedic surgeons. Because of the expanding indications for total knee arthroplasty (TKA) and an aging population with increasingly active lifestyles there has been a corresponding increase in the prevalence of these injuries. The management of these fractures is often complex because of issues with obtaining fixation around implants and dealing with osteopenic bone or compromised bone stock. In addition, these injuries frequently occur in frail, elderly patients, and the early restoration of function and ambulation is critical in these patients. There remains substantial controversy with respect to the optimal treatment of periprosthetic distal femur fractures, with some advocating for Locked Plating (LP), others Retrograde Intramedullary Nailing (RIMN) and finally those who advocate for Distal Femoral Replacement (DFR). The literature comparing these treatments, has been infrequent, and commonly restricted to single-center studies. The purpose of this study was to retrospectively evaluate a large series of operatively treated periprosthetic distal femur fractures from multiple centers and compare treatment strategies.

Patients who were treated operatively for a periprosthetic distal femur fracture at 8 centers across North America between 2003 and 2018 were retrospectively identified. Baseline characteristics, surgical details and post-operative clinical outcomes were collected from patients meeting inclusion criteria. Inclusion criteria were patients aged 18 and older, any displaced operatively treated periprosthetic femur fracture and documented 1 year follow-up. Patients with other major lower extremity trauma or ipsilateral total hip replacement were excluded. Patients were divided into 3 groups depending on the type of fixation received: Locked Plating, Retrograde Intramedullary Nailing and Distal Femoral Replacement. Documented clinical follow-up was reviewed at 2 weeks, 3 months, 6 months and 1 year following surgery. Outcome and covariate measures were assessed using basic descriptive statistics. Categorical variables, including the rate of re-operation, were compared across the three treatment groups using Fisher Exact Test.

In total, 121 patients (male: 21% / female: 79%) from 8 centers were included in our analysis. Sixty-seven patients were treated with Locked Plating, 15 with Retrograde Intramedullary Nailing, and 39 were treated with Distal Femoral Replacement. At 1 year, 64% of LP patients showed radiographic union compared to 77% in the RIMN group (p=0.747). Between the 3 groups, we did not find any significant differences in ambulation, return to work and complication rates at 6 months and 1 year (Table 1). Reoperation rates at 1 year were 27% in the LP group (17 reoperations), 16% in the DFR group (6 reoperations) and 0% in the RIMN group. These differences were not statistically significant (p=0.058).

We evaluated a large multicenter series of operatively treated periprosthetic distal femur fractures in this study. We did not find any statistically significant differences at 1 year between treatment groups in this study. There was a trend towards a lower rate of reoperation in the Retrograde Intramedullary Nailing group that should be evaluated further with prospective studies.

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There has been a substantial increase in the surgical treatment of unstable chest wall injuries recently. While a variety of fixation methods exist, most surgeons have used plate and screw fixation. Rib-specific locking plate systems are available, however evidence supporting their use over less-expensive, conventional plate systems (such as pelvic reconstruction plates) is lacking. We sought to address this by comparing outcomes between locking plates and non-locking plates in a cohort of patients from a prior randomized trial who received surgical stabilization of their unstable chest wall injury.

We used data from the surgical group of a previous multi-centred, prospective, randomized controlled trial comparing surgical fixation of acute, unstable chest wall injuries to non-operative management. In this substudy, our primary outcome was hardware-related complications and re-operation. Secondary outcomes included ventilator free days (VFDs) in the first 28 days following injury, length of ICU and hospital stay, and general health outcomes (SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores). Categorical variables are reported as frequency counts and percentages and the two groups were compared using Fisher's Exact test. Continuous data are reported as median and interquartile range and the two groups were compared using the Wilcoxon rank-sum test.

From the original cohort of 207 patients, 108 had been treated surgically and had data available on the type of plate construct used. Fifty-nine patients (55%) had received fixation with non-locking plates (primarily 3.5 or 2.7 mm pelvic reconstruction plates) and 49 (45%) had received fixation with locking plates (primarily rib-specific locking plates). The two groups were similar in regard to baseline and injury characteristics. In the non-locking group, 15% of patients (9/59) had evidence of hardware loosening versus 4% (2/49 patients) in the locking group (p = 0.1). The rate of re-operation for hardware complications was 3% in the non-locking group versus 0% in the locking group (p = 0.5). No patients in either group required revision fixation for loss of reduction or nonunion. There were no differences between the groups with regard to VFDs (26.3 [19.6 – 28] vs. 27.3 [18.3 – 28], p = 0.83), length of ICU stay (6.5 [2.0 – 13.1] vs 4.1 [0 – 11], p = 0.12), length of hospital stay (17 [10 – 32] vs. 17 [10 – 24], p = 0.94) or SF-36 PCS (40.9 [33.6 – 51.0] vs 43.4 [34.1 – 49.6], p = 0.93) or MCS scores (47.8 [36.9 – 57.9] vs 46.9 [40.5 – 57.4], p = 0.95).

We found no statistically significant differences in outcomes between patients who received surgical stabilization of their unstable chest wall injury when comparing non-locking plates versus locking plates. However, the rate of hardware loosening was nearly 4 times higher in the non-locking plate group and trended towards statistical significance, although re-operation related to this was less frequent. This finding is not surprising, given the inherent challenges of rib fixation including thin bones, comminution, potential osteopenia and a post-operative environment of constant motion. We believe that the increased cost of locking plate fixation in this setting is likely justifiable given these findings.

To systematically review the literature regarding post-surgical treatment regimens on ankle fractures, specifically whether there is a benefit to early weightbearing or early mobilization (6 weeks form surgery).

The PubMed, MEDLINE and Embase databases were searched from inception to May 24, 2020. All randomized controlled trials that analyzed the effects of early weightbearing and mobilization following an ankle surgery were included. The primary outcome measure was the Olerud Molander Ankle Score (OMAS). Secondary outcomes included return to work (RTW) and complications. Logistic regression models with random intercepts were used to pool complication data by protocol clustered by study.

Twelve RCT's were included, with a total of 1177 patients (41.8 ± 8.4 years). In total, 413 patients underwent early weightbearing and early mobilization (35%), 338 patients underwent early weightbearing and delayed mobilization (29%), 287 patients underwent delayed weightbearing and early mobilization (24%), and 139 patients underwent delayed weightbearing and delayed mobilization (12%). In total, 81 patients had a complication (7%), including 53 wound complications (5%), 11 deep vein thromboses (1%), and 2 failures/nonunions (0%). Early ankle mobilization resulted in statistically significant increases in OMAS scores compared to delayed mobilization (3 studies [222 patients], 12.65; 95% CI, 7.07-18.22; P < 0.00001, I2 = 49%). No significant differences were found between early and delayed weightbearing at a minimum of one-year follow-up (3 studies [377 patients], 1.91; 95% CI, −0.73-4.55, P = 0.16, I2 = 0%). Patients treated with early weightbearing and early mobilization were at higher odds of facing any complication (OR 3.6, 95%CI 1.05-12.1, p=0.041) or wound complications (OR 4.9, 95%CI 1.3-18.8, p=0.022) compared to those with delayed weightbearing and delayed mobilization.

Early mobilization following surgical treatment for an ankle fracture resulted in improved ankle function scores compared to delayed mobilization regimens. There were no significant differences between early and delayed weightbearing with respect to patient reported outcomes. Patients who were treated with early mobilization and early weightbearing had an increased odds of postoperative complications.

Unstable chest wall injuries have high rates of mortality and morbidity. These injuries can lead to respiratory dysfunction, and are associated with high rates of pneumonia, sepsis, prolonged ICU stays, and increased health care costs. Numerous studies have demonstrated improved outcomes with surgical fixation compared to non-operative treatment. However, an adequately powered multi-centre randomized controlled study using modern fixation techniques has been lacking.

We present a multi-centred, prospective, randomized controlled trial comparing surgical fixation of acute, unstable chest wall injuries with the current standard of non-operative management. Patients aged 16–85 with a flail chest (3 or more consecutive, segmental, displaced rib fractures), or severe deformity of the chest wall, were recruited from multiple trauma centers across North America. Exclusion criteria included: severe pulmonary contusion, severe head trauma, randomization>72 hours from injury, inability to perform surgical fixation within 96 hours from injury (in those randomized to surgery), fractures of the floating ribs, or fractures adjacent to the spine not amendable to surgical fixation. Patients were seen in follow-up for one year. The primary outcome was days free from mechanical ventilation in the first 28 days following injury. Secondary outcomes were days in ICU, rates of pneumonia, sepsis, need for tracheostomy, mortality, general health outcomes, pulmonary function testing, and other complications of treatment. A sample size of 206 was required to detect a difference of 2 ventilator-free days between the two groups, using a 2-tailed alpha error of 0.05 and a power of 0.80.

A total of 207 patients were recruited from 15 sites across Canada and USA, from 2011–2018. Ninety-nine patients were randomized to non-operative treatment, and 108 were randomized to surgical fixation. Overall, the mean age was 53 years, and 75% of patients were male, with 25% females. The commonest mechanisms of injury were: motor vehicle collisions (34%), falls (20%), motorcycle collisions (14%), and pedestrian injuries (11%). The mean injury severity score (ISS) at admission was 26, and patients had a mean of 10 rib fractures. Eighty-nine percent of patients had pneumothorax, 76% had haemothorax, and 54% had pulmonary contusion. There were no differences between the two groups in terms of demographics. The final results will be available and presented at the COA meeting in Halifax.

This is the largest randomized controlled trial to date, comparing surgical fixation to non-operative treatment of unstable chest wall and flail chest injuries. The results of this study will shed light on the best treatment options for patients with such injuries, help understand outcomes, and guide treatment. The final results will be available and presented at the COA meeting in Halifax.

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Distracted driving is now the number one cause of death among teenagers in the United States of America according to the National Highway Traffic Safety Administration. However, the risks and consequences of driving while distracted spans all ages, gender, and ethnicity. The Distractions on the Road: Injury eValuation in Surgery And FracturE Clinics (DRIVSAFE) Study aimed to examine the prevalence of distracted driving among patients attending hospital-based orthopaedic surgery fracture clinics. We further aimed to explore factors associated with distracted driving.

In a large, multi-center prospective observational study, we recruited 1378 adult patients with injuries treated across four clinics (Hamilton, Ontario, Toronto, Ontario, Calgary, Alberta, Halifax, Nova Scotia) across Canada. Eligible patients included those who held a valid driver's license and were able to communicate and understand written english. Patients were administered questions about distracted driving. Data were analyzed with descriptive statistics.

Patients average age was 45.8 years old (range 16 – 87), 54.3% male, and 44.6% female (1.1% not disclosed). Of 1361 patients, 1358 self-reported distracted driving (99.8%). Common sources of distractions included talking to passengers (98.7%), outer-vehicle distractions (95.5%), eating/drinking (90.4%), music listening/adjusting the radio (97.6%/93.8%), singing (83.2%), accepting phone calls (65.6%) and daydreaming (61.2%). Seventy-nine patients (6.3%), reported having been stopped by police for using a handheld device in the past. Among 113 drivers who disclosed the cause of their injury as a motor vehicle crash (MVC), 20 of them (17%) acknowledged being distracted at the time of the crash. Of the participants surveyed, 729 reported that during their lifetime they had been the driver in a MVC, with 226 (31.1%) acknowledging they were distracted at the time of the crash.

Approximately, 1 in 6 participants in this study had a MVC where they reported to be distracted. Despite the overwhelming knowledge that distracted driving is dangerous and the recognition by participants that it can be dangerous, a staggering amount of drivers engage in distracted driving on a fairly routine basis. This study demonstrates an ongoing need for research and driver education to reduce distracted driving and its devastating consequences.

The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing.

The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small animal model, this study aimed to determine the impact on the induced membrane of impregnating spacers with antibiotics frequently used in the IMT.

We surgically created a five-mm segmental defect in the right femur of 25 adult male Sprague Dawley rats. The bone was stabilized with a plate and screws before filling the defect with a PMMA spacer. Animals were divided into five equal groups according to the type and dose of antibiotics impregnated in the spacer: A) no antibiotic (control), B) low-dose tobramycin (1.2 g/40 g of PMMA), C) low-dose vancomycin (1 g/40 g of PMMA), D) high-dose tobramycin (3.6 g/40 g of PMMA), E) high-dose vancomycin (3 g/40 g of PMMA). The animals were euthanized three weeks after surgery and the induced membranes were collected and divided for analysis. We assessed the expression of selected genes (Alpl, Ctgf, Runx2, Tgfb1, Vegfa) within the membrane by quantitative real-time PCR. Moreover, frozen sections of the specimens were used to quantify vascularity by immunohistochemistry (CD31 antigen), proliferative cells by immunofluorescence (Ki-67 antigen), and membrane thickness. Microscopic images of the entire tissue sections were taken and analyzed using FIJI software. Finally, we measured the concentration of vascular endothelial growth factor (VEGF) in the membranes by ELISA.

No significant difference was found among the groups regarding the expression of genes related to osteogenesis (Alpl, Runx2), angiogenesis (Vegfa), or synthesis of extracellular matrix (Ctgf, Tgfb1) (n = four or five). Similarly, the density of proliferative cells and blood vessels within the membrane, as well as the membrane thickness, did not vary substantially between the control, low-dose, or high-dose antibiotic groups (n = four or five). The concentration of VEGF was also not significantly influenced by the treatment received (n = four or five).

The addition of tobramycin or vancomycin to the spacer, at the defined low and high doses, does not significantly alter the bioactive characteristics of the membrane. These results suggest that orthopaedic surgeons could use antibiotic-impregnated spacers for the IMT without compromising the induced membrane and potentially bone healing.

Rotator cuff injuries represent a significant burden to the health care system, affecting more than 30% of the population over the age of sixty. Despite the advanced surgical techniques that are available, poor results are sometimes seen in a subset of patients receiving surgical treatment for their rotator cuff disease. The reasons for this failure of treatment remain unclear, particularly if the surgery was ‘technically’ successful. An increasing body of evidence has demonstrated a strong correlation between pre-operative psychological factors and functional outcome following several orthopaedic procedures. This association, however, has not been fully demonstrated or effectively investigated in the context of rotator cuff treatment. The main objective for this study was to conduct a systematic review to determine the impact of psychosocial factors on the outcome of treatment in patients with rotator cuff disease.

A systematic search was conducted of Medline, CINAHL, and PsychInfo databases for articles published from database inception until September 2018. The titles and abstracts were screened for all of the studies obtained from the initial search. Inclusion and exclusion criteria were applied, and a full text review was conducted on those studies meeting the eligibility criteria.

A total of 1252 studies were identified. Following removal of duplicates and application of the inclusion and exclusion criteria, 46 studies underwent a full-text review. Ten studies were included in the final analysis. A total of 1,206 patients, with a mean follow-up of 13 months, were included. Three studies examined patient expectations prior to treatment. All three found that higher expectations prior to treatment led to a significantly improved outcome following both operative and non-operative treatment.

Three studies assessed the association between pre-operative general psychological measures and post-operative pain and function. All three studies found patients with worse pre-operative general psychological scores demonstrated increased post-operative pain. Two of the studies also found a negative association with post-operative function, while one of the studies found no association with post-operative function. Three studies assessed the impact of pre-operative anxiety and depression on outcomes following surgical treatment of rotator cuff disease. Only one of the studies found a negative association with post-operative pain and function. The remaining two studies found no association between anxiety or depression and any outcomes following surgery. Finally, one study examined the impact of general distress on outcomes following the surgical treatment of rotator cuff disease and found no association with post-operative levels of pain or function.

The results of this systematic review indicate that there is somewhat conflicting and contradictory evidence within the literature. Overall, however, there does appear to be an association between pre-operative psychological factors and post-operative function and pain, in that higher levels of pre-operative psychological dysfunction are predictive of poorer function and increased pain following the treatment of rotator cuff disease.

Aims

The purpose of this study was to compare the effectiveness of surgical repair to conservative treatment and subacromial decompression for the treatment of chronic/degenerative tears of the rotator cuff.

Proximal humerus fractures are a common fragility fracture in older adults. A variety of treatment options exist, yet longer term outcomes of newer surgical treatments have not been extensively researched. Additionally, intermediate term outcomes following both surgical and non-surgical initial treatment of these injuries have not been evaluated at a population level. The purpose of this study was to utilise administrative data from Ontario, Canada to evaluate intermediate term outcomes following initial treatment of proximal humerus fractures.

We used data from the Canadian Institute for Health Information to identify all patients aged 50 and older who presented to an ambulatory care facility with a “main diagnosis” of proximal humerus fracture from April 1, 2004 to March 31, 2013. Intervention codes from the Discharge Abstract Database were used to categorise patients into fixation, replacement, reduction or non-surgically treated groups. We used intervention codes to identify instances of complication-related operations following initial treatment (including fixation, replacement, hardware removal, rotator cuff repair and irrigation and debridement [I&D]) at one year post initial treatment.

The majority of patients (28,369, 86.6%, 95% confidence interval [95% CI] 86.2–87.0%) were initially treated non-surgically, while 2835 (8.7%, 95% CI 8.4–9.0%) underwent initial fixation, 1280 (3.9%, 95% CI 3.7–4.1%) received primary joint replacement, and 276 (0.8%, 95% CI 0.8–1.0%) were initially treated with a reduction procedure. In the year following the initial treatment period, 127 (0.4%, 95%CI 0.4–0.5%) non-surgically treated patients underwent a replacement surgery, 292 (1.0%, 95%CI 0.9–1.2%) underwent fixation, and 12 (0.04%, 95% CI 0.02–0.07%) underwent a reduction procedure. Of the 2835 patients who received initial fixation, 57 (2.0%, 95% CI 1.6–2.6%) returned for a shoulder replacement, 80 received secondary fixation (2.8%, 95% CI 2.3–3.5%), 57 (2.0%, 95%CI 1.6–2.6%) underwent rotator cuff repair, 300 (10.6%, 95% CI 9.5–11.8%) had their implants removed, and 16 (0.6%, 95% CI 0.4–0.9%) returned for I&D. Of the 1280 patients who underwent initial replacement surgeries, 30 (2.3%, 95% CI 1.7–3.3%) returned for a secondary replacement, nine (0.7%, 95% CI 0.4–1.3%) underwent rotator cuff repair, and seven (0.6%, 95% CI 0.3–1.1%) had their implant removed. In the group who received initial reduction, eight (2.9%, 95% CI 1.5–5.6%) underwent a fixation procedure, six (2.2%, 95% CI 1.0–4.7%) received replacement surgeries, and five (1.8%, 95% CI 0.8–4.2%) each received rotator cuff repair and I&D in the year following initial treatment.

The majority of proximal humerus fractures in patients 50 and older in Ontario, Canada are treated non-surgically. Complication-related operations in the year following initial non-operative treatment are relatively low. The most commonly observed procedure following initial fixation surgery is hardware removal.

Proximal femur fractures are increasing in prevalence, with femoral neck (FN) and intertrochanteric (IT) fractures representing the majority of these injuries. The salvage procedure for failed open reduction internal fixation (ORIF) is often a conversion to total hip arthroplasty (THA). The use of THA for failed ORIF improves pain and function, however the procedure is more challenging. The aim of this study was to investigate the clinical and radiographic outcomes in patients who have undergone THA after ORIF.

This retrospective case-control study compared patients who underwent THA after failed ORIF to a matched cohort undergoing primary THA for non-traumatic osteoarthritis. From 2004 to 2014, 40 patients were identified. The matched cohort was matched for date of operation, age, gender, and type of implant. Preoperative, intraoperative, and postoperative data were collected and statistical analysis was performed.

The cohort of patients with a salvage THA included 18 male and 22 female patients with a mean age of 73 years and mean follow up of 3.1 years. Those with failed fixation included 12 IT fractures and 28 FN fractures. The mean time between ORIF and THA was 2.1 years for IT fractures and 8.5 years for FN fractures (p=0.03). The failed fixation group had longer procedures, greater drop in hemoglobin, and greater blood transfusion rate (p<0.05). There was one revision and one dislocation in the failed fixation group with no revisions or dislocations in the primary THA group. Length of admission, medical complications, and functional outcome as assessed with a standardised hip score and were found not to be statistically different between the groups.

Salvage THA for failed initial fixation of proximal femur fractures yields comparable clinical results to primary THA with an increased operative time, blood loss, and blood transfusion rate.

Introduction

Nonunion is a common and costly fracture outcome. Intricate reciprocity between angiogenesis and osteogenesis means vascular cell-based therapy offers a novel approach to stimulating bone regeneration.

Purpose

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological and microCT evaluations (Atesok, Li, Schemitsch 2010); EPC treatment of fractures resulted in a significantly higher strength by biomechanical examination (Li, Schemitsch 2010). In addition, cell-based VEGF gene transfer has been effective in the treatment of segmental bone defects in a rabbit model (Li, Schemitsch et al 2009); Purpose of this study: Evaluation of VEGF gene expression after EPC local therapy for a rat segmental bone defect.

Purpose: Severe fractures damage blood vessels and disrupt circulation at the fracture site resulting in an increased risk of poor fracture healing. Endothelial progenitor cells (EPCs) are bone-marrow derived cells with the ability to differentiate into endothelial cells and contribute to neovascularization and re-endothelialization after tissue injury and ischemia. We have previously reported that EPC therapy resulted in improved radiographic healing and histological blood vessel formation in a rat fracture model. The purpose of this study was to further quantify the effects of EPC therapy with microCT and biomechanical analyses.

Method: Five-millimeter segmental defects were created and stabilized in the femora of 14 fisher 344 rats. The treatment group (n=7) received 1x106 EPCs within gelfoam locally at the area of the bone defect and control animals (n=7) received only saline-gelfoam with no cells. The formation and healing of bone after 10 weeks were asessed by radiographic, micro-CT and biomechanical analyses.

Results: Radiographically all the animals in EPC-treated group healed with bridging callus formation, whereas control group animals demonstrated radiographic non-union. Micro-CT assessment demonstrated significantly improved parameters of bone volume (35.34 to 20.68 mm³, p=0.000), bone volume density (0.24 to 0.13%, p=0.001), connectivity density (25.13 to 6.15%, p=0.030), trabecular number (1.14 to 0.51 1/mm, p=0.000), trabecular thickness (0.21 to 0.26 mm, p=0.011), trabecular spacing (0.71 to 1.88 mm, p=0.002), bone surface area (335.85 to 159.43mm, p=0.000), and bone surface to bone volume ratio (9.43 to 7.82 1/mm, p=0.013) in the defect site for the EPC group versus the control group respectively. Biomechanical testing showed that the EPC treatment group had a significantly higher torsional strength compared with the control group (EPC=164.6±27.9 Nmm, Control=29.5±3.8 Nmm; p value = 0.000). Similarly, the EPC treated fractures demonstrated significantly higher torsional stiffness versus controls (EPC=30.3±5.0 Nmm/ deg, Control=0.9±0.1 Nmm/deg; p value = 0.000). When biomechanically compared to contralateral intact limbs, the EPC treated limbs had similar torsional stiffness (p=0.996), but significantly lower torsional strength (p=0.000) and smaller angle of twist (p=0.002).

Conclusion: These results suggest that local EPC therapy significantly enhances fracture healing in an animal model. The biomechanical results show that control animals develop a mechanically unstable non-union. In contrast, EPC therapy results in fracture healing that restores the biomechanical properties of the fractured bone closer to that of intact bone.

Purpose: The purpose of this study was to compare the effects of two types of stem/progenitor cells on the healing of critical sized bone defects in a rat model. Endothelial Progenitor Cells (EPCs), a novel cell type with previously demonstrated effects on angiogenesis in animal models of vascular disease, were compared to both a control group of no cell therapy, and a treatment group of Mesenchymal Stem Cells (MSCs). The hypothesis was that EPCs would demonstrate both superior bone healing and angiogenesis, when compared to the control group and MSC group.

Method: EPCs and MSCs were isolated from the bone marrow of syngeneic rats by differential culture and grown ex vivo for 10 days. Subsequently the cells were harvested, seeded on a gelfoam scaffold, and implanted into a 5mm segmental defect in a rat femur that had been stabilized with a plate and screws. Bone healing was assessed radiographically and by microCT. Angiogenesis was assessed by histology and physiologically, using laser doppler to assess blood flow in the bone and soft tissues. All animal protocols were approved by and performed in accordance with the St. Michael’s Hospital Animal Care Committee. ANOVA was used to test for significant differences between the groups, and a p-value of < 0.05 was considered statistically significant.

Results: The EPC (n=14) group demonstrated radiographic evidence of healing of the bone defect as early as 2 weeks, and all specimens were radiographically healed at 6 weeks. Both the control group (n=14) and the MSC group (n=14) showed no radiographic evidence of healing at 10 weeks. MicroCT comparison of the EPC group versus the control group showed significantly greater bone volume and density at the defect site (p< 0.001). More blood vessel formation was observed in the EPC group versus the control group on histology at 2 weeks. Laser Doppler assessment showed significantly more soft tissue and bone blood flow at 2 and 3 weeks in the EPC group versus the control group (p=0.021).

Conclusion: The results of this study demonstrate that EPCs are effective as cell-based therapy for healing critical sized bone defects in a rat model. In this model EPCs demonstrated superiority to MSCs with regard to bone healing. In addition, EPCs demonstrated superior angiogenesis over controls in a rat model of fracture healing. These results strongly suggest that EPCs are effective for therapeutic angiogenesis and osteogenesis in fracture healing. There is a clinical need for effective strategies in the management of traumatic bone defects and nonunions. Investigation into the use of MSCs as an effective alternative to autologous bone grafting has failed to translate into clinical use. It is possible that EPCs are more effective at the regeneration of bone in segmental defects because of their synergistic effect on angiogenesis and osteogenesis. Further research into EPC based therapies for fracture healing is warranted.