The extracellular matrix (ECM)-based biomaterial can mimic the intervertebral disc (IVD) microenvironment, aiming to facilitate stem cell transplantation for tissue regeneration and modulate pain. We hypothesised that by altering the macromolecule weight ratios of ECM content in formulating hydrogel, we might guide the human umbilical cord Wharton Jelly-derived mesenchymal stem cell towards a nucleus pulposus (NP)-like phenotype in vitro and modulate pain in vivo. Herein, we developed a 3D hyaluronic acid (HA)/collagen (COLII)-based hydrogel at various weight ratios, which has been tested for physical properties, in vitro viability and NP phenotype, and in vivo implantation in a disc injury model of pain in the rat tail for the assessment of pain behaviour. We observed a higher swelling capacity in the hydrogel with a HA/COLII 4.5:9 weight ratio in comparison to 1:9, suggesting that a higher amount of HA can captivate a considerable amount of water. All hydrogel formulations demonstrated a comparable enzymatic degradation and were resistant to the hydrolytic process. We observed higher cell viability and rounded-morphology cells of MSC-encapsulated on hydrogel for 14 days. In vivo, we revealed that the surgically induced disc injury evoked mechanical allodynia without impairing health status in rats. We demonstrated the implantation of hydrogel to prevent injury-induced mechanical allodynia slightly. The tuneable HA/COLII hydrogel that exhibits optimal swelling property, stability, and degradability can mimic the 3D NP microenvironment to guide stem cells toward the NP phenotype, thus supporting stem cell transplantation for IVD regeneration targeting pain.

Introduction: The present study aims at testing our proof of concept that a novel patellar locking hook plate (HP) with its unique design will be relatively bio-mechanically equivalent compared to a standard available patellar poly-axial locking Suture-Plate (SP-Arthrex) by performing a finite element analysis (FEA). Material and methods:3-dimensional Finite element models of the two-part fractured patella-plate construct were created using the Computer-aided designing software. Constraining the upper and lower poles of the patella, 3.5 MPa and 4.4 MPa were applied on the models, simulating the physiological load acting upon the patella at 45o and 90o of knee flexion. Results: The maximum von Mises stress values for HP and SP were noted to be 587.7 MPa and 290.8 MPa respectively at 45o of knee flexion. The values of the von Mises stress for HP and SP at 90o of knee flexion were 720.6 MPa and 449.9 MPa respectively. The displacement values for HP and SP were analysed to be 0.94 mm and 0.366 mm respectively-well within the 2mm acceptable range. The displacement values for HP and SP were noted as 1.174 mm and 0.675 mm respectively. Lower profile of HP (2mm) than SP 3 versus 3.5mm is a major advantage with equivalent stress profile. Conclusion: Novel patellar HP for the surgical management of transverse two parts patellar fractures with its bio-mechanical results according to this comparative FEA is promising as results of stress generated were within the yield strength of the titanium metal alloy. Further study is warranted.

Cobalt (Co) ions, which can mimic hypoxia to promote angiogenesis, exhibit great potential for bone repair. However, a key point for the use of Co ions is that their release profile should be controllable, and, more importantly, suitable for the bone regeneration process. Here, 2-ethylimidazole (eIm) were introduced into zeolitic imidazolate framework-67 (ZIF-67) to slow down Co ion release and fabricate eIm-doped ZIF-67 (eIm/ZIF-67), which was combined into gelatin methacrylate (GelMA) to obtain an in situ photocrosslinking nanocomposite hydrogel as a tunable Co ion controlled release system. The tunable and controlled release of Co ions from the nanocomposite hydrogel was achieved by variation of linker composition, and that GelMA with 75% eIm/ZIF-67 (with 75% eIm in the precursor solutions) could maintain a 21-day sustained release of Co ions, which is matched with early-stage angiogenesis during the bone formation process. Our in vitro study also showed that the GelMA@eIm/ZIF-67 hydrogel could reduce cytotoxicity and effectively promote the angiogenic activity of human umbilical vein endothelial cells (HUVECs) and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, an in vivo rat calvarial defect model demonstrated that the GelMA@eIm/ZIF-67 hydrogel exhibited remarkably enhanced bone formation and neovascularization abilities and had good biocompatibility as shown in organ histopathological examinations. Therefore, this novel nanocomposite hydrogel has strong therapeutic potential as a desirable Co ion controlled release system and a powerful proangiogenic/osteogenic agent for the treatment of bone defects.

Introduction: Chondrosarcoma is the second most common neoplasm arising from skeletal tissue. There is currently no known marker to differentiate early chondrosarcoma from benign chondroid lesions and the molecular mechanism underlying the pathogenesis of chondrosarcoma is poorly understood. Method: Using single cell RNA sequencing (scRNAseq) technology, we characterised primary tumour tissues from patient (n=6 total) undergoing surgery for enchondroma (n=1) and low to high grade chondrosarcoma (n=5). Transcriptomic analysis identifies tumor cell subtypes, tumor microenvironment and molecular pathways involved in malignant transformation of chondroid lesions. Histological analysis with immunocytochemistry was used to revalidate clinical diagnosis and markers for neoplastic transformation identified. Results: Our transcriptomic analysis identified a total of eight cell subpopulations in the patient derived tumor samples collected. Importantly, a distinct population of cells was identified in the early chondrosarcoma samples. Bioinformatic analysis revealed two genes involved in endoplasmic reticulum stress namely; DDIT3 and ATF5, were up regulated during early malignant change in chondroid lesions. Immunocytochemistry performed on six benign chondroid lesions and three low-medium chondrosarcoma patient samples confirmed DDIT3 and ATF5 as a marker for early malignant change in chondroid lesions. Conclusion: The present study is the first study to characterize chondroid lesions at single-cell resolution. Using bioinformatic and histological analysis, this study identified DDIT3 and ATF5 as a potential marker which can used to detect early malignant transformation in chondroid lesion and may aid clinical decision making.

Reconstructive options of large intercalary defects at the femur following resection have historically included massive allograft secured with plate and screw fixation. Particularly in the adult population, limitations of allograft reconstruction include weightbearing restrictions, infection risk, and mechanical failure. Mechanical properties of allograft are limited by processing that devitalizes tissue, increasing fracture risk and diminishing osteoinductive capabilities associated with union and prevention of resorption. Recent alternative options for segmental bone defects have included reconstruction with a Ti6Al4V cylinder that is fixed in the bone defect by proximal and distal cemented intramedullary rods (IDSF; Merete OsteoBridge). In a preliminary study, we compared the biomechanical properties of 10 paired human cadaveric femurs in which a 7 cm segmental defect was repaired with IDSF (10) or with bulk allograft. The bulk allograft was fixed within the defect using one (5) or two plates (5). Pair matched femurs were tested by cyclical medial-lateral and anterior-posterior bending (300-800N), cyclical axial compression (300-800N), cyclical torsion (-6Nm to +6Nm), and internal rotation to failure. When compared to the single plate construct, IDSF had a statistically higher elastic stiffness in A/P and M/L bending (1096.3 ±483N/mm vs.363±56N/mm P=0.027, 827.8 ±152N/mm vs. 137.4 ± 48N/mm P<0.001, respectively) and torsional rigidity (178.1±46N*m/rad vs. 23.9 ±6N*m/rad P=0.002). When compared to the double plate construct, IDSF had a statistically higher elastic stiffness in A/P (1239.1 ± 228N/mm vs. 643.3 ± 184N/mm P=0.002) and torsional rigidity (192.9 ±37N*m/rad vs. 71.9 ±55.8N*m/rad P=0.005).

Osteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and the synovium. While it is still believed to be a mechanically driven disease, the role of underlying co-existing inflammatory processes and mediators in the onset of OA and its progression is now more appreciated. Post-traumatic osteoarthritis (PTOA) is a subtype of OA that occurs secondary to traumatic joint insults and widely used in pre-clinical models to help understand OA as a whole. There are currently no approved treatments for OA, so there is an urgent need to develop new treatments. In this review, we focus on the recent pharmacological advances in the treatment of OA and summarizes the most significant promising agents, based on their molecular effects, and are classified here into broad categories: anti-inflammatory, modulation of the activity of matrix metalloproteases, anabolic, and unconventional pleiotropic agents. We provide a comprehensive analysis of the pharmacological advances in each of these areas and highlight future insights and directions in the OA field.