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With the gradual demographic shift toward an aging and obese society, an increasing number of patients are suffering from bone and cartilage injuries. However, conventional therapies are hindered by the defects of materials, failing to adequately stimulate the necessary cellular response to promote sufficient cartilage regeneration, bone remodeling and osseointegration. In recent years, the rapid development of nanomedicine has initiated a revolution in orthopedics, especially in tissue engineering and regenerative medicine, due to their capacity to effectively stimulate cellular responses on a nanoscale with enhanced drug loading efficiency, targeted capability, increased mechanical properties and improved uptake rate, resulting in an improved therapeutic effect. Therefore, a comprehensive review of advancements in nanomedicine for bone and cartilage diseases is timely and beneficial. This review firstly summarized the wide range of existing nanotechnology applications in the medical field. The progressive development of nano delivery systems in nanomedicine, including nanoparticles and biomimetic techniques, which are lacking in the current literature, is further described. More importantly, we also highlighted the research advancements of nanomedicine in bone and cartilage repair using the latest preclinical and clinical examples, and further discussed the research directions of nano-therapies in future clinical practice. Graphical Abstract

The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready‐to‐use product with well‐defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte‐MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra‐articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging‐based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications. We summarize the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and trophic factors regulating mesenchymal stromal cell (MSC) activity in vivo, as well as multiple approaches for cell tracking and labeling in vitro and in vivo. Understanding the distribution and persistence of MSCs is necessary to fully realize potential cartilage regeneration techniques and tissue engineering applications.

Osteoarthritis (OA), the commonest arthritis, is characterized by the progressive destruction of cartilage, leading to disability. The Current early clinical treatment strategy for OA often centers on anti‐inflammatory or analgesia medication, weight loss, improved muscular function and articular cartilage repair. Although these treatments can relieve symptoms, OA tends to be progressive, and most patients require arthroplasty at the terminal stages of OA. Recent studies have shown a close correlation between joint pain, inflammation, cartilage destruction and synovial cells. Consequently, understanding the potential mechanisms associated with the action of synovial cells in OA could be beneficial for the clinical management of OA. Therefore, this review comprehensively describes the biological functions of synovial cells, the synovium, together with the pathological changes of synovial cells in OA, and the interaction between the cartilage and synovium, which is lacking in the present literature. Additionally, therapeutic approaches based on synovial cells for OA treatment are further discussed from a clinical perspective, highlighting a new direction in the treatment of OA.

Objectives: To investigate variables associated with improvement in quality of life (QOL) after primary knee replacement. QOL outcomes between individuals undergoing total knee replacement (TKR) and unicompartmental knee replacement (UKR) were compared. Materials and Methods: Participants were adults ( n = 497) undergoing TKR or UKR for osteoarthritis between January 2017 and October 2020 in a large publicly funded tertiary hospital in New Zealand. Participants completed patient‐reported outcome measures of QOL, pain and function, preoperatively, 6 and 12 months postoperatively. Results: QOL improved pre‐ to postoperatively for both TKR and UKR groups, and the main QOL gains for both groups were evident in the first 6 months after joint replacement. Notably, QOL did not differ between groups at any assessment point ( p > 0.05). Improvement in QOL was more correlated with improved pain and function than with person factors such as demographics and comorbidity burden ( p < 0.01). Conclusions: This study adds to a growing literature showing that knee replacement contributes to substantial improvements in QOL outcomes. Future QOL outcome research in the knee replacement population should consider using more precise measures of function to better understand the impacts of these factors on QOL improvement.

While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis. This facile bioassembly platform to study cartilage–cartilage interfaces offers a powerful route to probe multicellular fusion mechanisms in developmental stages of tissue growth and regenerative repair strategies. This hybrid 3D‐bioassembly model provides a bridge between understanding, tissue fusion and cellular differentiation by recapitulating detailed biological mechanisms in vitro—systematically unlocking the potential of tissue growth and subsequent organ engineering.

Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation. Urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) levels were analysed in 28 knee and 22 hip arthroplasty patients pre- and post-operatively to determine oxidative stress and inflammation levels. Total neopterin was 31.1% higher with knee arthroplasty (p<0.05). Urinary neopterin was 32.8% higher in the knee arthroplasty group versus hips. The increase in neopterin and total neopterin following a post-surgical decrease in levels was significant in both groups. Levels of neopterin and total neopterin were varied between patients, but all increased following surgery and subsided by day 28. The increased levels of urinary neopterin and total neopterin from knee arthroplasty indicate that knee osteoarthritis and arthroplasty is a more significant trauma to the body than hip osteoarthritis and arthroplasty surgery. This is also shown by faster inflammatory resolution following hip arthroplasty.

Purpose We examined associations between self-reported and clinician-assessed comorbidity and quality of life (QOL) outcomes after hip and knee replacement. Methods This is a cross-sectional, questionnaire-based national survey. Participants aged 45 years or older ( n  = 409) were recruited from the New Zealand Joint Registry six months after a total hip (THR), total knee (TKR) or unicompartmental knee replacement (UKR). The main outcome QOL was measured using an 8-item short form of the World Health Organisation Quality of Life (WHOQOL-Bref) questionnaire six months following joint replacement surgery. The WHOQOL is a generic and non-health condition specific measure of QOL. Results Participants were on average 68 years of age, with more men (54%) than women (46%). Number of coexisting conditions and body mass index were correlated with age, pain and function scores, and QOL ( p  < 0.01), but not with each other. Linear regression analyses showed that comorbidities such as number of comorbid conditions and BMI had moderate associations with QOL outcomes. Conclusion This study showed that general QOL outcomes following hip and knee joint replacement, while generally high, were associated with comorbidity burden and BMI. Future prospective research examining change in QOL before and following surgery would help to advance understandings of the various factors that contribute to patient satisfaction with their joint replacement.

Performs a retrospective audit of patient characteristics, surgical management practices, rehabilitation practices and outcomes, osteoporosis treatment prescription and mortality for patients with hip fractures admitted to Christchurch Hospital. Compares outcomes for four groups : 1) publicly funded aged residential care (ARC) residents discharged directly from acute orthopaedics, 2) non-ARC residents discharged directly from acute orthopaedics, 3) patients discharged after orthogeriatric rehabilitation and 4) patients discharged after general geriatric rehabilitation. Looks also at the differences between orthogeriatric and general geriatric rehabilitation groups in respect to length of stay, comorbidities, functional status and treatment for osteoporosis. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Background: Arthroscopic meniscectomy often results in rapid recovery and return to preinjury activities; however, postoperative hemarthrosis and swelling can lead to pain, decreased range of motion, and delayed return to work and leisure activities. Tranexamic acid (TXA) is a lysine-based inhibitor of plasminogen to plasmin that has gained popularity in arthroplasty surgery for reducing blood loss and, more recently, in anterior cruciate ligament reconstruction by reducing postoperative hemarthrosis, swelling, and pain while increasing function in the short term. Purpose: To determine whether there is a role for TXA in improving the short-term results of swelling, pain, and function following arthroscopic meniscectomy. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: We performed a prospective double-blinded randomized controlled trial in 41 patients undergoing arthroscopic meniscectomy by comparing patients treated with intravenous TXA with those treated with a placebo (normal saline). A single surgeon treated all patients. Following randomization, a dose of 1 g of TXA in 100 mL of normal saline (treatment group) or 100 mL of normal saline (placebo group) was given intravenously at induction prior to tourniquet inflation by the anesthetist. The anesthetist administering the TXA or placebo was not blinded, but all other clinicians involved were. Patients were evaluated by a blinded observer at postoperative days 3, 14, and 30, with the range of motion, swelling, pain levels (visual analog scale), and Lysholm and Tegner knee scores recorded. Results: Patient demographics were similar in both groups. In the treatment group, there was a nonsignificant improvement in range of motion (P = .056) and swelling (P = .384) at 14 days; however, there was a significant improvement in the Tegner score at 3 days (P = .0064). The complication profile was similar between the groups. Conclusion: The administration of 1 g of intravenous TXA in routine arthroscopic meniscectomy may improve early functional recovery without increased risk. A larger study is required to confirm these results and further evaluate any potential benefit. Registration: ACTRN12618001600235 (Australian New Zealand Clinical Trials Registry).

Purpose Reducing participant burden is important in health research and clinical assessment. We examined the psychometric properties of the EUROHIS-QOL 8-item index, a short version of the 26-item World Health Organisation Quality of Life questionnaire (WHOQOL-Bref), in a sample of people receiving joint replacement surgery. Methods Participants (n = 1008) completed the WHOQOL-Bref at either 6, 12, 24 or 60 months after hip or knee replacement. The factor structure, differential item functioning (DIF) and unidimensionality of the EUROHIS-QOL 8-item index were examined using exploratory and confirmatory factor analyses and Rasch analyses. Convergent validity was examined using correlations with the parent measure and other patient-reported outcome measures (Oxford scores, Western Ontario and McMaster Universities Osteoarthritis Index). Discriminant validity was assessed between groups reporting high versus low pain and function, and by joint replaced. Results The measure demonstrated high internal consistency (α = 0.86), adequate convergent (r = 0.47-0.82, p < 0.001) and discriminant validity (p < 0.001). Factor and Rasch analyses supported a unidimensional structure. However, there were also indications of multidimensionality, with support for a two-factor model focusing on general health and function, and psychosocial aspects of QOL. There was minimal evidence of DIF, with just one item evaluating energy level showing DIF for age. Conclusions The EUROHIS-QOL 8-item index demonstrated adequate properties as a unidimensional scale and as a two-factor scale evaluating general health and function, and psychosocial aspects of quality of life. It is low on clinical and participant burden, showed minimal ceiling effects and showed good concurrent and discriminant validity.