Systematic review of artificial intelligence tack in preventive orthopaedics: is the land coming soon?

PURPOSE: This study aims to describe and assess the current stage of the artificial intelligence (AI) technology integration in preventive orthopaedics of the knee and hip joints. MATERIALS AND METHODS: The study was conducted in strict compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Literature databases were searched for articles describing the development and validation of AI models aimed at diagnosing knee or hip joint pathologies or predicting their development or course in patients. The quality of the included articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and QUADAS-AI tools. RESULTS: 56 articles were found that meet all the inclusion criteria. We identified two problems that block the full integration of AI into the routine of an orthopaedic physician. The first of them is related to the insufficient amount, variety and quality of data for training, and validation and testing of AI models. The second problem is the rarity of rational evaluation of models, which is why their real quality cannot always be evaluated. CONCLUSION: The vastness and relevance of the studied topic are beyond doubt. Qualitative and optimally validated models exist in all four scopes considered. Additional optimization and confirmation of the models' quality on various datasets are the last technical stumbling blocks for creating usable software and integrating them into the routine of an orthopaedic physician.

Gender-Related Aspects in Osteoarthritis Development and Progression: A Review.

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions.

Lactoferrin as a regenerative agent: The old-new panacea?

Lactoferrin (Lf) possesses various biological properties and therapeutic potentials being a perspective anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, and immunomodulatory agent. A significant body of literature has also demonstrated that Lf modulates regenerative processes in different anatomical structures, such as bone, cartilage, skin, mucosa, cornea, tendon, vasculature, and adipose tissue. Hence, this review collected and analyzed the data on the regenerative effects of Lf, as well as paid specific attention to their molecular basis. Furthermore, tissue and condition-specific activities of different Lf types as well as problems of their delivery to the targeted organs were discussed. The authors strongly hope that this review will stimulate researchers to focus on the highlighted topics thus accelerating the progress of Lf's wider clinical application.

Autologous bone marrow-derived mesenchymal stem cells provide complete regeneration in a rabbit model of the Achilles tendon bundle rupture.

PURPOSE: To ascertain the role of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in the tendon regeneration. METHODS: The study was conducted on 58 Achilles tendons from 29 laboratory Chinchilla adult rabbits. The central bundles of 48 tendons were partially removed and substituted with a tissue-engineered construct consisting of a collagen sponge either loaded with BM-MSCs (n = 24) or cell free (n = 24), placed inside a Vicryl mesh tube. The ends of the resected tendon were inserted in the construct to reach a direct contact with the sponge and sutured to the tube. The animals were sacrificed three and six months post-surgery. Ten intact tendons from five rabbits were used as an untreated control. The tissue samples (n = 30) were stained with haematoxylin and eosin, Picrosirius red, primary antibodies to collagen types I and III and studied by bright-field, phase-contrast, polarized light, and scanning electron microscopies followed by semi-quantitative morphometry. RESULTS: Six months results of cell-loaded scaffolds demonstrated parallel collagen fibres, spindle-shaped tenocytes, and neoangiogenesis. In the control cell-free group, the injured areas were filled with a nonspecific fibrotic tissue with minor foci of incomplete regeneration. The biomechanical tests of 28 tendons taken from 14 rabbits showed that the stiffness of the cell-based reconstructed tendons increased to 98% of the value for the intact samples. CONCLUSION: The obtained results support the hypothesis that the application of BM-MSCs in a tissue-engineered tendon construct leads to the restitution of the tendon tissue.

C-reactive protein as marker of post-operative analgesic quality after primary total knee arthroplasty.

OBJECTIVE: To study the correlation between the level of C-reactive protein (CRP) and the severity of pain in the post-operative period with primary total knee arthroplasty and to conduct a comparative assessment of these indicators with various methods of pain relief. The primary hypothesis of the investigation was that post-operative CRP level is likely to be correlated with the severity of post-operative pain after total knee arthroplasty. The secondary points were the evaluation of CRP and pain syndrome in the groups, as well as the identification of the correlation between the level of CRP and the method of analgesia. MATERIALS AND METHODS: Peri-operative levels of CRP and pain syndrome (10-point visual analogue scale) studied 160 patients with grade III gonarthrosis who have underwent primary total knee arthroplasty under conditions of subarachnoid anaesthesia in the period from years 2017 to 2019. Depending on the method of post-operative analgesia, patients were divided into five groups: group 1 had only systemic multimodal analgesia (SMA, n = 56), group 2 were treated with the epidural analgesia (EDA, n = 20), group 3 had local high-volume infiltration anaesthesia (LHVIA, n = 20), group 4 were getting LHVIA with a wound catheter (LHVIAc, n = 48), and group 5 had a single blockade of the femoral nerve (FNB, n = 16). RESULTS: A direct strong correlation was obtained between the level of CRP and the severity of pain syndrome in the knee joint during movement in four to six hours after surgery (n = 160, Kendall coefficient τ = 0.230, p = 0,000) and on the first post-operative day (n = 160, τ = 0.21, p = 0.001). The increase in CRP (the difference between pre-operative and post-operative CRP levels) also was positively correlated with the severity of pain in the post-operative period (n = 160, τ = 0.257, p = 0.000 and τ = 0.187, p = 0.001, respectively). CRP level significantly has increased in the post-operative period (p = 0,000). The lowest CRP indicators in the first post-operative day were recorded during the infiltrative anaesthesia (3rd and 4th groups);, the highest were during the administration of SMA group (1st group). CONCLUSION: The results confirm the correlation between the level of CRP and the severity of pain syndrome in the early post-operative period after total knee arthroplasty, its dependence on the method of analgesia, and allow to use it as a criterion for evaluating of the effectiveness of analgesia.

Arthroscopic synovectomy of the knee joint for rheumatoid arthritis.

OBJECTIVE: To investigate the effect of knee arthroscopic synovectomy (AS) on the disease activity, quality-of-life (QoL), and the functional status of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: A retrospective analysis was conducted on the outcomes of AS performed on 138 RA patients; pre-surgery assessments were done using Disease Activity score (DAS 28) and Routine Assessment of Patient Index Data З (RAPID-3) on а multidimensional health-assessment questionnaire for disease activity, EuroQol-5D (EQ-5D) and the Short-Form Medical Outcomes Study (SF-36) for quality of life, and the Health Assessment Questionnaire (HAQ) for functional status. The pain response to SA was measured by а visual analogue score (VAS) and the Knee Society Score (KSS). RESULTS: All parameters assessed in the study showed significant positive changes: the activity of the disease decreased, and patients' functional status and QoL improved. CONCLUSION: AS is effective treatment for recurrent synovitis of the knee in RA patients. This technique improves the functional status of patients and their quality of life and reduces the activity of the disease.

The degree of cartilage degradation assessed by serum biomarker levels changes after arthroscopic knee synovectomy in rheumatoid arthritis patients.

PURPOSE: In order to test the validity of the selected surgical technique as a way to manage persistent synovitis of the knee joint, as well as to slow down the cartilage and bone destruction, we studied the dynamics of biomarkers of inflammatory conditions, and bone and cartilage destruction after total arthroscopic synovectomy (TAS) of the knee joint. METHODS: The sampling comprised 124 RA patients (158 knees) who had undergone the TAS procedure between 2003 and 2015. Before surgery the rheumatoid factor (IgM), C-reactive protein (CRP), erythrocyte sedimentation rate test was completed for all patients. Blood serum samples were collected (prior to surgery, and three, six and 12 months after surgery) and frozen at -70°Ð¡. The content of CRP, Matrix metalloproteinase-3 (MMP-3), Cartilage Oligomeric Matrix Protein, as well as cross-linked Ctelopeptides of types I and II were measured in blood serum by means of polarization fluoroimmunoassay with the use of a standard set of reagents. RESULTS: The average duration of the disease in the studied group was 8.7 ± 6.6 years. Concentration of the inflammation markers showed that only MMP-3 displayed statistical significance. CONCLUSIONS: The obtained results can be used as basis in assessing the efficiency and effectiveness of this method of treatment of persistent knee joint synovitis associated with the RA.

No Significant Differences between Bisphosphonates and Placebo for the Treatment of Bone Marrow Lesions of the Knee: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: The purpose of the present systematic review and meta-analysis is to summarize the current evidence on the role of bisphosphonates in the treatment of knee bone marrow lesions (BMLs), to understand whether they are truly effective in improving symptoms and restoring the subchondral bone status at imaging evaluation. Methods: A literature search was carried out on PubMed, Cochrane, and Google Scholar databases in accordance with the PRISMA guidelines. Potential risk of bias was evaluated using the Cochrane Risk of Bias 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies. Results: A total of 15 studies were included in the present systematic review and meta-analysis. Seven studies were RCTs, two were prospective cohort studies, three were retrospective, and three were case series. Our meta-analysis revealed that bisphosphonates did not significantly improve clinical scores or reduce BML size compared to placebo. Accordingly, the rate of adverse events was also non-significantly higher among bisphosphonate users versus placebo users. Conclusions: The main finding of the present meta-analysis and systematic review is that bisphosphonates show neither significant benefits nor significant adverse events when compared to placebo in the treatment of BMLs of the knee. Level of Evidence: Level IV systematic review of level II-III-IV studies. Level I meta-analysis of level I studies.

Diffuse reflectance spectroscopy of the cartilage tissue in the fourth optical window.

Studies of the optical properties of biological tissues in the infrared range have demonstrated significant potential for diagnostic tasks. One of the insufficiently explored ranges for diagnostic problems at the moment is the fourth transparency window, or short wavelength infrared region II (SWIR II). A Cr2+:ZnSe laser with tuning capability in the range from 2.1 to 2.4 µm was developed to explore the possibilities in this region. The capability of diffuse reflectance spectroscopy to analyze water and collagen content in biosamples was investigated using the optical gelatin phantoms and the cartilage tissue samples during their drying process. It was demonstrated that decomposition components of the optical density spectra correlated with the partial content of the collagen and water in the samples. The present study indicates the possibility of using this spectral range for the development of diagnostic methods, in particular, for observation of the changes in the content of cartilage tissue components in degenerative diseases such as osteoarthritis.

Grading cartilage damage with diffuse reflectance spectroscopy: Optical markers and mechanical properties.

Osteoarthritis (OA) is one of the most common joint diseases worldwide. Unfortunately, clinical methods lack the ability to detect OA in the early stages. Timely detection of the knee joint degradation at the level of tissue changes can prevent its progressive damage. Here, diffuse reflectance spectroscopy (DRS) in the NIR range was used to obtain optical markers of the cartilage damage grades and to assess its mechanical properties. It was observed that the water content obtained by DRS strongly correlates with the cartilage thickness (R = .82) and viscoelastic relaxation time (R = .7). Moreover, the spectral parameters, including water content (OH-band), protein content (CH-band), and scattering parameters allowed for discrimination between the cartilage damage grades (10-4 < P ≤ 10-3 ). The developed approach may become a valuable addition to arthroscopy, helping to identify lesions at the microscopic level in the early stages of OA and complement the surgical analysis.

Biologic agents to optimize outcomes following ACL repair and reconstruction: A systematic review of clinical evidence.

Treatment options for anterior cruciate ligament (ACL) injuries have greatly developed over the past decades. Although reconstruction surgery is a concrete reality, stimulation of ACL healing through biological techniques could represent a revolutionary conservative approach. The use of biologic products, such as platelet-rich plasma (PRP) or mesenchymal stem cells (MSCs), to treat partial ruptures or to enhance ligamentization after reconstruction, could thoroughly improve clinical outcomes. The aim of the present paper is to systematically review the available literature on this topic, to (i) describe the current state of the art in available biologic techniques; (ii) clarify the outcomes of their application; (iii) identify areas needing further investigation and possible future development. A systematic review of the literature on the use of biologically active agents (PRP and MSCs) to enhance outcomes of ACL surgery was performed: 31 studies were included. Based on the ACL injury pattern, 6 papers investigated biologic agents in ACL partial tears whereas 25 papers in ACL reconstruction. Sixteen of twenty-five studies dealing with ACL reconstruction were randomized controlled trials, whereas only case series are available for partial ACL tears. Current evidence is still lacking sound data to support the use of biological agents: no clinical superiority has been described when using PRP in ACL reconstruction. Concerning ACL healing in partial tears, the application of PRP has led to encouraging outcomes, but these findings should be confirmed by appropriately designed RCTs.

A defined road to tracheal reconstruction: laser structuring and cell support for rapid clinic translation.

One of the severe complications occurring because of the patient's intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses-the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials.

Fibrin-based Bioinks: New Tricks from an Old Dog.

For the past 10 years, the main efforts of most bioprinting research teams have focused on creating new bioink formulations, rather than inventing new printing set-up concepts. New tissue-specific bioinks with good printability, shape fidelity, and biocompatibility are based on "old" (well-known) biomaterials, particularly fibrin. While the interest in fibrin-based bioinks is constantly growing, it is essential to provide a framework of material's properties and trends. This review aims to describe the fibrin properties and application in three-dimensional bioprinting and provide a view on further development of fibrin-based bioinks.

Engineering a Model to Study Viral Infections: Bioprinting, Microfluidics, and Organoids to Defeat Coronavirus Disease 2019 (COVID-19).

While the number of studies related to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is constantly growing, it is essential to provide a framework of modeling viral infections. Therefore, this review aims to describe the background presented by earlier used models for viral studies and an approach to design an "ideal" tissue model for SARS-CoV-2 infection. Due to the previous successful achievements in antiviral research and tissue engineering, combining the emerging techniques such as bioprinting, microfluidics, and organoid formation are considered to be one of the best approaches to form in vitro tissue models. The fabrication of an integrated multi-tissue bioprinted platform tailored for SARS-CoV-2 infection can be a great breakthrough that can help defeat coronavirus disease in 2019.