Intervertebral disc (IVD) degeneration plays a major role in low back pain which is the leading cause of disability. Current treatments in severe cases require surgical intervention often leading to adjacent segment degeneration. Injectable hydrogels have received much attention in recent years as scaffolds for seeding cells to replenish disc cellularity and restore disc properties and function. However, they generally present poor mechanical properties. In this study, we investigated several novel thermosensitive chitosan hydrogels for their ability to mimic the mechanical properties of the nucleus pulposus (NP) while being able to sustain the viability of NP cells, and retain proteoglycans.

CH hydrogels were prepared by mixing the acidic chitosan solution (2% w/v) with various combinations of three gelling agents: sodium hydrogen carbonate (SHC) and/or beta-glycerophosphate (BGP) and/or phosphate buffer (PB) (either BGP0.4M, SHC0.075M-BGP0.1M, SHC0.075M-PB0.02M or SHC0.075M-PB0.04M). The gelation speed was assessed by following rheological properties within 1h at 37°C (strain 5% and 1Hz). The mechanical properties were characterized and compared with that of human NP tissues. Elastic properties of the hydrogels were studied by evaluating the secant modulus in unconfined compression. Equilibrium modulus was also measured, using an incremental stress-relaxation test 24h after gelation in unconfined compression (5% strain at 5%/s followed by 5min relaxation, five steps). Cells from bovine IVD were encapsulated in CH-based gels and maintained in culture for 14 days. Cytocompatibility was assessed by measuring cell viability, metabolism and DNA content. Glycosaminoglycan (GAG) synthesis (retained in the gel and released) was determined using DMMB assay. Finally injectability was tested using human cadaveric discs.

Unconfined compression confirmed drastically enhanced mechanical properties compared to conventional CH-BGP hydrogels (secant Young modulus of 105 kPa for SHC0.075PB0.02 versus 3–6 kPa for BGP0.04). More importantly, SHC0.075PB0.02 and SHC0.075BGP0.1 hydrogels exhibited mechanical properties very similar to NP tissue. For instance, equilibrium modulus was 5.2±0.6 KPa for SHC0.075PB0.02 and 8±0.8 KPa for SHC0.075BGP0.1 compared to 6.1±1.7 KPa for human NP tissue. Rheological properties and gelation time (G′=G″ after less than 15 s at 37°C, and rapid increase of G') of these hydrogels also appear to be adapted to this application. Cell survival was greater than 80% in SHC0.075BGP0.1 and SHC0.075PB0.02 hydrogels. Cells encapsulated in the new formulations also showed significantly higher metabolic activity and DNA content after 14 days of incubation compared to cells encapsulated in BGP0.4 hydrogel. Cells encapsulated in SHC0.075BGP0.1 and SHC0.075PB0.02 produced significantly higher amounts of glycosaminoglycans (GAG) compared to cells encapsulated in SHC0.075PB0.04 and BGP0.4 hydrogels. The total amount of GAG was higher in SHC0.075BGP0.1 hydrogel compared to SHC0.075PB0.02. Interestingly, both the SHC0.075BGP0.1 and SHC0.075PB0.02 hydrogels retained similar amounts of GAG. Injectability through a 25G syringe, filling of nuclear clefts and good retention in human degenerated discs was demonstrated for SHC0.075PB0.02 hydrogel.

SHC0.075BGP0.1 appears to be a particularly promising injectable scaffold for IVD repair by providing suitable structural environment for cell survival, ECM production and mechanical properties very similar to that of NP tissue.

Recent innovations in total ankle replacement (TAR) have led to improvements in implant survivorship, accuracy of component positioning and sizing, and patient outcomes. CT-generated pre-operative plans and cutting guides show promising results in terms of placement enhancement and reproducibility in clinical studies. The purpose of this study was to determine the accuracy of 1) implant sizes used and 2) alignment corrections obtained intraoperatively using the cutting guides provided, compared to what was predicted in the CT generated pre-operative plans.

This is a retrospective study looking at 36 patients who underwent total ankle arthroplasty using a CT generated pre-operative planning system between July 2015 and December 2017. Personalized pre-operative planning data was obtained from the implant company. Two evaluators took measurements of the angle corrected using pre- and post-operative weight bearing ankle AP X-rays. All patients had a minimum three-month follow-up with weightbearing postoperative radiographs. The actual correction calculated from the radiographic assessment was compared with the predicted angles obtained from pre-operative plans. The predicted and predicted alternative component sizes and actual sizes used were also compared. If either a predicted or predicted alternative size was implanted, we considered it to be accurate.

Average age for all patients was 64 years (range 40–83), with a body mass index of 28.2 ± 5.6. All surgeries were performed by two foot and ankle surgeons. The average total surgical time was 110 ± 23 minutes. Pre-operative alignment ranged from 36.7 degrees valgus to 20 degrees varus. Average predicted coronal alignment correction was 0.8 degrees varus ± 9.3 degrees (range, 18.2 degrees valgus to 29 degrees varus) and average correction obtained was 2.1 degrees valgus ± 11.1 degrees. Average post-op alignment was consistently within 5 degrees of neutral. There were no significant differences between the predicted alignments and the postoperative weightbearing alignments. The predicted tibia implant size was accurate in all cases. The predicted sizes were less accurate for talar implants and predicted the actual talar implant size used in 66% of cases. In all cases of predicted talar size mismatch, surgical plans predicted 1 implant size larger than used.

Preliminary analyses of our data is comparable to previous studies looking at similar outcomes. However, our study had higher pre-operative deformities. Despite that, post-op alignments were consistently within 5 degress of neutral with no significant difference between the predicted and actual corrections. Tibial implant sizes are highly accurate while talar implant sizes had a trend of being one size smaller than predicted. Moreover, this effect seems to be more pronounced in the earlier cases likely reflective of increasing surgeon comfort with the implant with each subsequent case. These results confirm that pre-operative cutting guides are indeed helpful in intra-operative implant selection and positioning, however, there is still some room for innovation.

Utilising the (ACS-NSQIP) database, we aimed to evaluate the impact of resident level of training on surgical outcome following (TKA) and to compare the US and Canadian health care training system in regards to 30 days postoperative complications and readmission rates.

Using the (CPT) codes we selected from the 2011 and 2012 NSQIP database elective primary TKA with the resident surgeon involved. Of these, all cases with a primary diagnosis code of infection, fracture, mechanical complication, or malignancy and all cases with incomplete or incongruous demographic information were excluded. We also eliminated all the cases with the Attending not present. A total of 2513 cases were included in the study. The cases were stratified into three groups according to the postgraduate level of training {PGY 1 to 3 (junior resident), PGY 4 to 5 (senior resident), and fellow}. Univariate analysis of all patient demographics, comorbidities, intra and postoperative variables, length of surgery, hospital stay and 30 days readmission rates were conducted in order to identify differences between the groups. A standard student's t test was used for continuous variables while the ChiSquared was used for categorical variables. Multivariable logistic regression models were created to assess the independent effect of the resident level of training on the 30 days major complication and re-admission rates while controlling for all other variables.

We identified, 854 (34%) TKAs with junior residents, 1013 (40%) TKAs with senior residents and 646 (26%) TKAs with fellows' participation. Junior residents had a significant (p<0.0001) longer operative time (107±36 minutes) compared with senior residents and fellows. Length of hospital stay was longer in the fellow group probably because of their involvement in more complicated cases. Additionally, an increased number of blood transfusion was observed for the cases performed with involvement of senior residents when compared with the other two groups. However, no significant difference in complications was observed across training levels. When comparing US (2074 TKAs) versus Canada (423 TKAs) cases, we found that fellow contribution to TKA surgeries is higher in Canada. The occurrence of pulmonary embolism and pneumonia was three times higher in Canada cases, while blood transfusion was more frequent in US. Increased operative time, ASA class, age, diabetes, percutaneous cardiac intervention, and steroid use were all independent risk factors for complications following primary TKA. However, no significant difference was observed between the two groups with regards to major complications suggesting no difference between Canadian and American training system in regards to post operative complication.

Our results support previous study study indicating that involvement of residents did not affect the surgical outcome within 30 days when compared to cases with no resident involvement. Our study suggests that resident level does not independently increase the risk of short term complications and support continuing involvement of junior trainees in TKA.

Hip resurfacing offers an attractive alternative to conventional total hip arthroplasty in young active patients. It is particularly advantageous for bone preservation for future revisions. Articular Surface Replacement (ASR) is a hip resurfacing prosthesis manufactured by DePuy Orthopaedics Inc. (Warsaw, IN). The manufacturer voluntarily recalled the ASR system in 2010 after an increasing number of product failures. The present study aimed to determine the long-term results in a large cohort of patients who received the ASR prosthesis.

Between February 2004 and August 2010, 592 consecutive hip resurfacings using the ASR (DePuy Orthopaedics Inc., Warsaw, IN) resurfacing implant were performed in 496 patients (391 males and 105 females). The mean age of the patients at the time of the surgery was 54 (range: 25 to 74) years. Osteoarthritis was the most common diagnosis in 575 hips (97.1%). The remaining patients (2.9%) developed secondary degenerative disease from ankylosing spondylitis, avascular necrosis, developmental hip dysplasia, and rheumatoid arthritis. Clinical and radiographic information was available for all patients at the last follow up. Cobalt (Co) and chromium (Cr) levels were measured in 265 patients (298 hips) by inductively coupled plasma-mass spectrometry (ICP-MS).

The average follow up of the study was 8.6 years (range: 5.2 to 11.6 years). The mean Harris hip and UCLA scores significantly improved from 44 and 2 pre-operatively to 85.3 and 7.1 respectively. The median Co and Cr ion level was 3.81 microgram per liter and 2.15 microgram per liter respectively. Twenty-seven patients (5.4%) were found to have blood levels of both Co and Cr ions that were greater than 7 microgram per liter. Fifty-four patients (9.1%) were revised to a total hip arthroplasty. Kaplan-Meier survival analysis showed a survival rate of 87.1% at 8.6 years with revision for any cause and 87.9% if infection is removed. A significantly higher survival rate was observed for the male patients (90.2%, p <0.0001) and for the patients with ASRs with femoral heads diameters larger than 52 mm (90.1%, p=0.0003).

This study confirms that patient selection criteria are of great importance to the overall survivorship of hip resurfacing arthroplasty. Improved clinical results have been reconfirmed with the use of larger diameter femoral heads.

Hip fractures are among the most common orthopaedic injuries and represent a growing burden on healthcare as our population ages. Despite improvements in preoperative optimisation, surgical technique and postoperative care, complication rates remain high. Time to surgery is one of the few variables that may be influenced by the medical team. The aim of the present study was to evaluate the impact of time to surgery on mortality and major complications following surgical fixation of hip fractures.

Utilising the American College of Surgeons' National Quality Improvement Program (NSQIP) database, we analysed all hip fractures (femoral neck, inter-trochanteric, and sub-trochanteric) treated from 2011 to 2013 inclusively. We divided patients into three groups based on time to surgery: less than one day (<24h), one to two days (24–48h), and two to five days (48–120h). Baseline characteristics were compared between groups and a multivariate analysis performed to compare 30-day mortality and major complications (return to surgery, deep wound infection, pneumonia, pulmonary embolus, acute renal failure, cerebrovascular accident, cardiac arrest, myocardial infarction, or coma) between groups.

A total of 14,730 patients underwent surgical fixation of a hip fracture and were included in our analysis. There were 3,475 (24%) treated <24h, 9,960 (67%) treated 24–48h, and 1,295 (9%) treated 48–120h. Thirty-day mortality and major complication rates were 5.0% and 6.2% for the <24h group, 5.3% and 7.0% for the 24–48h group, 7.9% and 9.7% for the 48–120h group respectively. After controlling for baseline demographic differences between groups (age, sex, race) as well as pertinent comorbidities (diabetes, dyspnea, chronic obstructive pulmonary disease, chronic steroid use, hypertension, cancer, bleeding disorders, and renal failure), time to surgery beyond 48h resulted in greater odds of both mortality (1.45, 95%CI 1.10–1.91) and major complications (1.45, 95%CI 1.12–1.84).

Time to surgery is one of the few variables that can be influenced by timely medical assessment and access to the operation room. Expediting surgery within 48h of hip fracture is of paramount importance as it may significantly reduce the risk of mortality as well as major complications.

Osteoarthritis (OA) is a multifactorial disease that affects millions of Canadians. Although, there is not one specific mechanism that causes OA, the biological outcome is cartilage degradation. The articular cartilage in joints is composed primarily of the proteoglycan aggrecan and type II collagen (Col II) which together provide cartilage with functional properties. In OA, the imbalance of the anabolic and catabolic activities of chondrocytes favors cartilage catalysis. The main inflammatory cytokine involved in cartilage degradation is interleukin (IL) 1β. It has previously been demonstrated that Link N, a 16 residue peptide derived from proteolytic cleavage of link protein, can stimulate matrix proteins in normal cartilage and intervertebral discs (IVDs). Recently, we showed that a shorter sequence of Link N (sLink N), consisting of the first 8 residues of the peptide, has the potential to increase synthesis of matrix proteins in IVD cells in vitro and stimulate repair in ex vivo IVD organ culture. There are currently no treatments that actively repair cartilage in OA joints. In the present study, we aimed to evaluate the potential of sLink N as a therapeutic agent in the repair of OA cartilage.

OA cartilage was isolated from four donors undergoing total knee replacement (50–70 y). Cells were recovered from the cartilage of each knee by sequential digestion with Pronase followed by Collagenase, and expanded in PrimeGrowth culture medium (Wisent Bioproducts, Canada; Cat# 319–510-CL, −S1, and −S2). After 7 days in culture, cells were treated for 24h with sLink N (0.5, 5, 50, 500 or 5000 ng/ml) or sLink N in combination with IL-1β (1 ng/ml) to mimic an inflammatory milieu. Conditioned media was collected and measured for proteoglycan (GAG) release using the safranin O and for Col II synthesis by Western blotting. Human articular cartilage explants including cartilage with subchondral bone were prepared from the same donors using the PrimeGrowth Isolation kit (Wisent, Canada) and cultured for 21 days in presence of IL-1β (1ng/ml) and sLink N (0.5, 5, 50, 500 or 5000 ng/ml). Aggrecan and Col II were extracted with guanidine buffer and measured by Western blotting.

Treatment of OA chondrocytes significantly increased the GAG and Col II synthesis. The EC50 dose-response of sLink N on GAG synthesis was 67 ± 41 nM [65 ± 40 ng/ml] and the GAG synthesis reached a maximum of 194 ± 30% with the highest dose above control. When chondrocytes were cultured in the presence of IL-1β, GAG synthesis was also elevated by sLink N above control. Treatment of OA cartilage explants with sLink N increased the content of aggrecan and Col II even in the presence of IL-1β.

Our results suggest that sLink N is a growth factor supplement that can increase cartilage matrix protein synthesis, and a chondroprotective agent, by modulating the catabolic effects of IL-1β. sLink N is the first small-peptide to demonstrate potential in cartilage repair of OA joints.

Testing potential therapeutics in the regeneration of the disc requires the use of model systems. Although several animal models have been developed to test intervertebral disc (IVD) regeneration, application becomes costly when used as a screening method. The bovine IVD organ culture system offers an inexpensive alternative, however, in the current paradigm, the bony vertebrae is removed to allow for nutrient diffusion to disc cells. This provides limitations on the conditions and strategies one can employ in investigating IVD regeneration and mechanisms in degenerative disc disease (i.e. complex loading). Although one method has been attempted to extend the survival of bovine vertebrae containing IVDs (vIVD) cell viability declined after two weeks in culture. Our goal was to develop and validate a long-term organ culture model with vertebral bone, which could be used subsequently for studying biological repair of disc degeneration and biomechanics.

Preparation of vIVDs: Bovine IVDs from the tails of 22–28-month-old steers were prepared for organ culture by parallel cuts through the adjacent vertebral bodies at 1cm from the endplates using an IsoMet®1000 Buehler precision sectioning saw. vIVDs were split into two groups: IVDs treated with PrimeGrowth Media kit (developed by Intervertech and licensed to Wisent Bioproducts) and IVDs with DMEM. The PrimeGrowth group was incubated for 1h in PrimeGrowth Isolation Medium (Cat# 319–511-EL) and the DMEM group for 1h in DMEM. After isolation, IVDs were washed in PrimeGrowth Neutralisation Medium (Cat# 319–512-CL) while the other IVDs were washed in DMEM. The discs isolated with PrimeGrowth and DMEM were cultured for up to 5 months in sterile vented 60 ml Leakbuster™ Specimen Containers in PrimeGrowth Culture Medium (Cat# 319–510-CL) and DMEM with no mechanical load applied. Live/Dead Assay: vIVDs cultured for 1 or 5 months were dissected and cell viability was assessed in different regions by confocal microscopy using Live/Dead® (Invitrogen) fluorescence assay. Glucose Diffusion: After one month of culture, vIVDs were incubated for 72h in diffusion medium containing PBS (1x), CaCl2 (1mM), MgCl2 (0.5mM), KCl2 (5mM), 0.1% BSA and 150µM 2-NDBG, a D-glucose fluorescent analogue. Discs were dissected and IVD tissues were incubated in guanidinium chloride extraction buffer. Extracts were measured for fluorescence.

After 5 months in culture, vIVDs prepared with PrimeGrowth kit demonstrated approximately 95% cell viability in all regions of the disc. However, dramatic reductions (∼90%) in vIVD viability were measured in DMEM group after 1 month. vIVD viability was related to the amount of 2-NDBG incorporated into the disc tissue.

We have developed a novel method for isolating IVDs with vertebral bone capable of long-term viability. This method may not only help in the discovery of novel therapeutics in disc regeneration, but could also advance our understanding on complex loading paradigms in disc degeneration.

Calcification of the intervertebral disc (IVD) has been correlated with degenerative disc disease (DDD), a common cause of low back pain. The appearance of calcium deposits has been shown to increase with age, and its occurrence has been associated with several other disorders such as hyperparathyroidism, chondrocalcinosis, and arthritis. Trauma, vertebral fusion and infection have also been shown to increase the incidence of IVD calcification. The role of IVD calcification in the development DDD is unknown. Our preliminary data suggest that ionic calcium content and expression of the extracellular calcium-sensing receptor (CaSR), a G protein-coupled receptor (GPCR) and regulator of calcium homeostasis, are increased in the degenerated discs. However, its role in DDD remains unclear.

IVD Cells: Bovine and normal human IVD cells were incubated in PrimeGrowth culture medium (Wisent Bioproducts, Canada; Cat# 319–510-CL, −S1, and S2) and supplemented with various concentrations of calcium (1.0, 1.5, 2.5, 5.0 mM), a CaSR agonist [5 µM], or IL-1β [10 ng/ml] for 7 days. Accumulated matrix protein was quantitated for aggrecan and type II collagen (Col II) by Western blotting. Conditioned medium was also collected from cells treated for 24h and measured for the synthesis and release of total proteoglycan using the DMMB assay and Western blotting for Col II content. IVD Cultures: Caudal IVDs from tails of 20–24 month old steers were isolated with the PrimeGrowth Isolation kit (Wisent Bioproducts, Canada). IVDs were cultured for 4 weeks in PrimeGrowth culture medium supplemented with calcium (1.0, 2.5, or 5.0 mM), or a CaSR agonist [5 µM]. Cell viability was measured in NP and AF tissue using Live/Dead Imaging kit (ThermoFisher, Waltham, MA), to determine if Ca2+ effects cell viability end the expression of aggrecan and Col II was evaluated in the IVD tissue by Western blotting. Histological sections were prepared to determine total proteoglycan content, alkaline phosphatase expression and degree of mineralisation by von Kossa staining.

The accumulation of aggrecan and Col II decreased dose-dependently in IVD cells following supplementation with calcium or the CaSR agonist. Conditioned medium also demonstrated decreases in the synthesis and release of proteoglycan and collagen with increasing Ca2+ dose or direct activation of the CaSR with agonist. A similar phenomenon was observed for total proteoglycan and aggrecan and Col II in IVDs following calcium supplementation or the CaSR agonist. In addition to decreases in Col II and aggrecan, increases in alkaline phosphatase expression and mineralisation was observed in IVDs cultured in elevated Ca2+ concentrations without affecting cell viability.

Our results suggest that changes in the local concentrations of calcium are not benign, and that activation of the CaSR may be a contributing factor in IVD degeneration. Determining ways to minimise Ca2+ infiltration into the disc may mitigate disc degeneration.