The 2020-2021 Canadian Residency Matching Service (CaRMS) match year was altered on an unprecedented scale. Visiting electives were cancelled at a national level, and the CaRMS interview tour was moved to a virtual model. These changes posed a significant challenge to both prospective students and program directors (PDs), requiring each party to employ alternative strategies to distinguish themselves throughout the match process. For a variety of reasons, including a decline in applicant interest secondary to reduced job prospects, the field of orthopaedic surgery was identified as vulnerable to many of these changes, creating a window of opportunity to evaluate their impacts on students and recruiting residency programs.

This longitudinal survey study was disseminated to match-year medical students (3rd and 4th year) with an interest in orthopaedic surgery, as well as orthopaedic surgery program directors. Responses to the survey were collected using an electronic form designed in Qualtrics (Qualtrics, 2021, Provo, Utah, USA). Students were contacted through social media posts, as well as by snowball sampling methods through appropriate medical student leadership intermediates. The survey was disseminated to all 17 orthopedic surgery program directors in Canada.

A pre-match and post-match iteration of this survey were designed to identify whether expectations differed from reality regarding the effect of the COVID-19 pandemic on the CaRMS match 2020-2021 process. A similar package was disseminated to Canadian orthopaedic surgery program directors pre-match, with an option to opt-in for a post-match survey follow-up. This survey had a focus on program directors’ opinions of various novel communication, recruitment, and assessment strategies, in the wake of the COVID-19 pandemic.

Students’ responses to the loss of visiting electives were negative. Despite a reduction in financial stress associated with reduced need to travel (p=0.001), this was identified as a core component of the clerkship experience. In the case of virtual interviews, students’ initial trepidation pre-CaRMS turned into a positive outlook post-CaRMS (significant improvement, p=0.009) indicating an overall satisfaction with the virtual interview format, despite some concerns about a reduction in their capacity to network. Program directors and selection committee faculty also felt positively about the virtual interview format. Both students and program directors were overwhelmingly positive about virtual events put on by both school programs and student-led initiatives to complement the CaRMS tour.

CaRMS was initially developed to facilitate the matching process for both students and programs alike. We hope to continue this tradition of student-led and student-informed change by providing three evidence-based recommendations. First, visiting electives should not be discontinued in future iterations of CaRMS if at all possible. Second, virtual interviews should be considered as an alternative approach to the CaRMS interview tour moving forward. And third, ongoing virtual events should be associated with a centralized platform from which programs can easily communicate virtual sessions to their target audience.

The purpose of this population-based study was to determine the association between morbid obesity and 10-year mortality and complications in patients undergoing primary THA.

A cohort study of 22,251 patients, aged 45–74 years old, treated with primary THA between 2002 and 2007 for osteoarthritis, was conducted using Ontario administrative healthcare databases. Patients were followed for 10 years. Risk ratios (RRs) of mortality, reoperation, revision, and dislocation in patients with body mass index (BMI) > 45 kg/m2(morbidly obese patients) compared with BMI ≤45 kg/m2 (non-morbidly obese) were estimated.

3.3% of the cohort (726) was morbidly obese. Morbidly obese patients were younger (mean age 60.6 vs. 63.3, P-value < 0 .001) and more likely to be female (63.9% vs. 52.2%, P-value < 0 .001), compared with non-morbidly obese patients. Morbid obesity was associated with higher 10-year risk of death (RR 1.38, 95% CI 1.18, 1.62). Risks of revision (RR 1.43, 95% CI 0.96, 2.13) and dislocation (RR 2.38, 95% CI 1.38, 4.10) were higher in morbidly obese men, compared with non-morbidly obese men, there were no associations between obesity and revision or dislocation in women. Risk of reoperation was higher in morbidly obese women, compared to non-morbidly obese women (RR 1.60, 95% CI 1.05, 2.40), there was no association between obesity and reoperation in men.

Morbidly obese patients undergoing primary THA are at higher risks of long-term mortality and complications. There were differences in complication risk by sex. Results should inform evidence-based perioperative counseling of morbidly obese patients considering THA.

Introduction

Computer-assisted methods for acetabulum cup navigation have shown to be able to improve the accuracy of the procedure, but are time-consuming and difficult to use. The goal of this project was to develop an easy-to-use navigation technique, requiring minimal equipment for acetabular cup alignment.

The ability to generate replacement human tissues on demand is a major clinical need. Indeed the paucity of techniques in reconstructive surgery and trauma emphasize the urgent requirement for alternative strategies for the formation of new tissues and organs. The idea of biomimesis is to abstract good design principles and optimizations from nature and incorporate them in the construction of synthetic materials and structures. Direct appropriation of natural inorganic skeletons is also biomimetic since their unique properties inform us on ways to generate functional, optimized scaffolds.

A number of well characterized natural skeletons were investigated as potential scaffolds for tissue regeneration using mesenchymal stem cell populations. Marine sponges, sea urchin skeletons and nacre were found to possess unique functional properties that supported human cell attachment, growth and proliferation and provided organic/ inorganic extracellular matrix analogues for guided tissue regeneration.

A good understanding of the processses involved in biomineralisation and the emergence of complex inorganic forms has inspired synthetic strategies for the formation of biological analogues (organised inorganic materials with biological form). We have developed two functional examples of biological structures generated using biomimetic materials chemistry with applications for human tissue regeneration. Mineralised biopoly-saccharide microcapsules provided enclosed micro-environments with an appropriate physical structure and physiological milieu, for the support of the initial stages of tissue regeneration combined with a capacity to deliver human cells, plasmid DNA and controlled release of biological factors such as cytokines. Calcium carbonate porous microspheres analogous to microscopic coccolithophore shells provided a template for tissue formation and a mechanism for the delivery of DNA and functional biological factors. These biomi-metic structures have considerable potential as scaffolds for skeletal repair and regeneration, particularly when combined with inductive and stimulatory biological factors (cytokines, morphogens, signal molecules) and plasmid DNA carrying with them chemical cues that modulate and direct permanent tissue formation complimentary with the host.

Polysaccharide (alginate and chitosan) capsules coated with a unique self-assembled semi-crystalline shell of calcium phosphate provide an enclosed biological system for the spatial and temporal delivery of human cells and bioactive factors. The aim of this study was to demonstrate plasmid DNA entrapment, delivery and transfection of adjacent cells inside capsules, embedded capsules and plated. Bacterial plasmid DNA and/or bone cells (SaOS) was added to solution of sodium alginate solution supplemented with phosphate ions and mixed thoroughly. Alginate droplets were fed through a syringe into a solution of chitosan supplemented with calcium ions. Guest capsules were inserted into soft, pliable host capsules soon after immersion in chitosan solution. Capsules were then immersed in 2mL DMEM 10% FCS in 6-well plastic plates for up to 7 days to enable transfection to occur. Encapsulated bone cells were stained with standard X-Gal to show transfected cells expressing beta-galactosidase. DNA delivery and transfection was demonstrated within capsules containing SaOS cells and plasmid, an admixture of SaOS bone cells and plasmid (51%) and from capsules containing DNA alone suspended in media over plated SaOS one cells. We also demonstrate capsule transfection of encapsulated cells in vivo. Transfection efficiency is highest when plasmid is entrapped and released from embedded capsules followed by plasmid/ SaOS admixture within capsules and lowest efficiency was observed with plated SaOS cells (with a transfection efficiency of 5%). The ability to regulate shell decomposition by manipulating the degree of mineralization and the strength of gelling, and release of capsule contents provides a mechanism for programmed release of gene modulated cells into the biological environment. The beta-galactosidase plasmid was found to be strongly associated with the chitosan/ calcium phosphate shell as shown by ethidium-homodimer-1 staining of encapsulated DNA and this may assist the transfer from gel to cell. Programmed non-viral delivery of genes using biomaterial constructs is an important approach to gene therapy and orchestrated tissue regeneration. These unique biomineralised polysaccharide capsules provide a facile technique, and an enclosed biomimetic micro-environments with specifiable degradation characteristics, for the safe encapsulation and delivery of functional quantities of plasmid DNA with the implicit therapeutic implications therein.

Introduction: The ability to generate bone for skeletal repair, replacement or restoration is a major clinical need. Indeed the paucity of techniques in reconstructive surgery and trauma emphasise the need for alternative bone formation strategies. Natural biological ceramic structures possess arrangements of structural elements that govern and optimise tissue function, nutrition and organisation. The aim of this study was to fabricate biomineral microporous shells with highly complex forms and to examine their ability to interact with human osteoprogenitor cells as cell and growth factor delivery vehicles.

Methods: Microporous vaterite shells were generated using a synthetic in-solution mineralisation technique in which mineral is spontaneously deposited around vesicular templates (Walsh and Mann 1999)* Porous and textured self-organising hollow microspheres (5–20 _m) were generated expressing controlled and uniform shapes. These micropores puncture the surface at high densities and are interconnected throughout the sphere. Primary human bone marrow cells labelled with Cell Tracker Green and ethidium homodimer-1 fluorescent labels and osteoprogenitors transfected with an adenoviral vector expressing Green Fluorescent Protein (AdGFP) were cultured with vaterite shells over three weeks.

Results: Cell biocompatibility of these biomimetic spheres was confirmed by confocal fluorescence and light microscopy in primary human bone marrow cultures labelled with CTG and bone marrow cultures transfected with AdGFP. At three weeks microspheres were encapsulated and integrated with osteoprogenitor cells. Histological analysis confirmed expression of alkaline phosphatase, extracellular matrix synthesis and the capacity for extensive mineralisation. Examination by SEM, fluorescent and light microscopy showed that the growth of osteoprogenitors transfected with AdGFP and microspheres in pellet culture showed vaterite spheres were encapsulated and integrated within the osteoprogenitor cell matrix indicating the potential of growth factor delivery. To determine the potential of the spheres to encapsulate selected proteins, microporous spheres were incubated with bovine haemoglobin. FITC microscopic evidence showed haemoglobin could be entrapped inside the spheres and between the biomineral crystal plates during self-assembly.

Discussion and Conclusion: These studies demonstrate the development of facile techniques for the generation of porous microsphere sponges that are biocompatible, possess the ability to aid mineralisation and for the delivery of cell and growth factors. These calcium carbonate structures provide a material with widespread application in a range of tissue engineering applications including skeletal tissue regeneration.

Introduction: The clinical need for a biodegradable material with broad application is evidenced by the fact that tissue loss as a result of injury or disease provides reduced quality of life for many at significant socio-economic cost. The development of simple biodegradable materials, with broad applicability and tissue/ cell specificity has to date proved elusive. Natural biopolymers such as alginate and chitosan are structural biomaterials of increasing significance to tissue repair and regeneration due to their potential for fabrication, design and efficient, environmentally benign synthesis. We describe the development of innovative microcapsule scaffolds based on chitosan and alginate that can be tailored to a range of cell types for a variety of tissues.

Methods: Semi-permeable polysaccharide microcapsules were produced by a one-step method, in which the deposition of a semi-permeable alginate/chitosan membrane around droplets of sodium alginate was coupled with in-situ precipitation of amorphous calcium phosphate as described by Leveque et al (2002)*. A variety of human cell types including mesenchymal stem cells, osteoprogenitors selected using the STRO-1 antibody by magnetically activated cell separation (MACS), osteoprogenitors transfected with adenovirus expressing Green Fluorescent Protein (GFP) and chondrocytes were mixed with sodium alginate and encapsulated within alginate/chitosan and calcium phosphate.

Results: Hybrid spheres (750–10,000um) were generated encapsulating primary human osteoprogenitor cells, STRO-1 selected osteoprogenitors and AdGFP transfected osteoprogenitors. Encapsulated cells remain viable inside the polysaccharide microcapsules for 2 weeks as shown by positive alkaline phosphatase staining of encapsulated cells. Cells expressing GFP were observed within microspheres indicating the e ability to deliver cells/factors as well as the potential for gene therapy. Encapsulation and delivery of active BMP-2 was confirmed using the promyoblast cell line C2C12 known to be exquisitely sensitive to BMP-2. Nucleation of calcium phosphate occurred within the polysaccharide membrane and could be controlled by the phosphate concentration in the alginate droplets to produce hybrid microcapsules with enhanced mechanical strength. Thin walled capsules were shown to split and degrade in culture within 2–4 days releasing viable osteoprogenitor cells indicating the ability to manipulate the mechanical integrity and to programme degradation of the microspheres. Finally we have shown that aggregation of the microspheres into extended frameworks can be achieved using a designed droplet/vapour aerosol system resulting in foams of aggregated beads.

Discussion and Conclusion: A variety of human skeletal cells have been encapsulated within polysaccharide/ calcium phosphate microspheres and extended frameworks with specifiable dimensions. These composite scaffolds offer stable mechanical and chemical biomimetic environments conducive to normal cell function. Natural polysaccharides are also highly amenable to complexation with a range of bioactive molecules and consequently offer tremendous potential in tissue engineering and regeneration of hard and soft tissues.