Management of hip osteoarthritis: harnessing the potential of mesenchymal stem cells-a systematic review.

INTRODUCTION: Hip osteoarthritis (OA) is a prevalent and debilitating condition, necessitating effective and safe treatment options. This systematic review aims to explore the potential of intra-articular mesenchymal stem cell (MSC) infiltrations as a therapeutic approach for hip OA. METHODS: Following PRISMA guidelines, a systematic review was conducted, encompassing PubMed, Embase, and Cochrane Library databases. Inclusion criteria involved studies focusing on intra-articular MSC injections in patients with hip OA and reporting pain relief as an outcome measure. Quality assessment utilized the Newcastle-Ottawa scale and methodological index for non-randomized studies. RESULTS: Ten studies were included in the review, exhibiting varied designs and sample sizes (316 patients). Outcome measures consisted of cartilage repair assessed through MRI and radiographies, pain scores (WOMAC, VAS, NRS), and functional improvements (HOS-ADL, OHS, FRI, PDQQ, LEFS). The studies reported favorable improvements in functional scores, pain relief, and cartilage repair/radiographic findings, with minimal reported adverse events. CONCLUSIONS: Intra-articular MSC infiltrations demonstrate promise as an effective and safe therapeutic intervention for managing hip OA, offering pain relief and functional enhancements. Nevertheless, limited high-quality studies and outcome measure variations underscore the need for further research to establish definitive treatment guidelines. Future investigations should address optimal MSC utilization, long-term outcomes, and potential complications to ensure the success of MSC-based therapies for hip OA management, ultimately improving patient outcomes. The findings provide valuable insights into the potential of MSC-based treatments for hip OA, advocating further rigorous research in this field. TRIAL REGISTRATION: The protocol was registered on PROSPERO database (CRD42023436973).

Clinical and Functional Outcomes of Kinematic Aligned Total Knee Arthroplasty with a Medial Pivot Design: Two-Year Follow-Up.

BACKGROUND: Kinematic alignment (KA) restores native limb alignment following total knee arthroplasty (TKA). The association of this technique with a medial pivot implant design attempts to re-establish the physiological kinematics of the knee. This study aims to analyze the clinical and radiological outcomes of patients undergoing MP-TKA with kinematic alignment and to assess the effect of limb alignment on the clinical outcomes. METHODS: We retrospectively analyzed 55 patients who underwent kinematic aligned medial pivot TKA from September 2018 to January 2020. Patient-related outcomes (PROMs) were collected at baseline, 3, 12, and 24 months after surgery. Long-standing weight-bearing radiographs were performed three months after surgery. RESULTS: We demonstrated a significant improvement in clinical outcomes from 3 months after surgery up to 24 months of follow-up. This clinical improvement was independent of limb alignment. The radiological analysis showed that the patient's native limb alignment was restored and that their joint line orientation was parallel to the floor. CONCLUSION: The association of kinematic alignment and a medial pivot TKA implant allows for a fast recovery, with good clinical and functional outcomes up to a minimum of 2 years of follow-up, independent of the final limb alignment.

Results and complications of bilateral limb lengthening in achondroplasia: a retrospective analysis.

Background: Achondroplasia is one of the main causes of disharmonic dwarfism. Patients with achondroplasia might have physical and psychological limitations due to their disproportionate stature. Surgical limb lengthening is the only practical option available to achieve a stature comparable to normal population range. The purpose of this study is to analyze results and complications of our lengthening protocol. Methods: A retrospective analysis was performed on 33 patients with achondroplasia (21 females and 12 males) undergoing simultaneous bilateral tibia or femur lengthening in four surgical stages from 2017 to 2021 (46 lengthening procedures, with a total of 56 tibias and 36 femurs). For each patient, patients' characteristics and antero-posterior and lateral radiographs were obtained. The following parameters were analyzed: duration of lengthening with external fixator, amount of lengthening, complications or events that influenced outcomes and the healing index (HI). Results: The average tibial and femoral gain was 7.9 cm and 6.9 cm, respectively. The tibiae achieved better results than the femurs (p = 0.005). Nineteen complications were reported for 92 segments (20.7%), and the variables influencing complications were: step (p = 0.002) and fixation duration (p = 0.061). Conclusions: Bilateral parallel lower limb lengthening in four surgical steps may be a viable technique in patients with achondroplasia.

Framing Patellar Instability: From Diagnosis to the Treatment of the First Episode.

The patellofemoral joint (PFJ) is a complex articulation between the patella and the femur which is involved in the extensor mechanism of the knee. Patellofemoral disorders can be classified into objective patellar instability, potential patellar instability, and patellofemoral pain syndrome. Anatomical factors such as trochlear dysplasia, patella alta, and the tibial tuberosity-trochlear groove (TT-TG) distance contribute to instability. Patellofemoral instability can result in various types of dislocations, and the frequency of dislocation can be categorized as recurrent, habitual, or permanent. Primary patellar dislocation requires diagnostic framing, including physical examination and imaging. Magnetic resonance imaging (MRI) is essential for assessing the extent of damage, such as bone bruises, osteochondral fractures, and medial patellofemoral ligament (MPFL) rupture. Treatment options for primary dislocation include urgent surgery for osteochondral fragments or conservative treatment for cases without lesions. Follow-up after treatment involves imaging screening and assessing principal and secondary factors of instability. Detecting and addressing these factors is crucial for preventing recurrent dislocations and optimizing patient outcomes.

In Vitro and In Vivo Biocompatibility Assessment of a Thermosensitive Injectable Chitosan-Based Hydrogel for Musculoskeletal Tissue Engineering.

Musculoskeletal impairments, especially cartilage and meniscus lesions, are some of the major contributors to disabilities. Thus, novel tissue engineering strategies are being developed to overcome these issues. In this study, the aim was to investigate the biocompatibility, in vitro and in vivo, of a thermosensitive, injectable chitosan-based hydrogel loaded with three different primary mesenchymal stromal cells. The cell types were human adipose-derived mesenchymal stromal cells (hASCs), human bone marrow stem cells (hBMSCs), and neonatal porcine infrapatellar fat-derived cells (IFPCs). For the in vitro study, the cells were encapsulated in sol-phase hydrogel, and then, analyzed via live/dead assay at 1, 4, 7, and 14 days to compare their capacity to survive in the hydrogel. To assess biocompatibility in vivo, cellularized scaffolds were subcutaneously implanted in the dorsal pouches of nude mice and analyzed at 4 and 12 weeks. Our data showed that all the different cell types survived (the live cell percentages were between 60 and 80 at all time points in vitro) and proliferated in the hydrogel (from very few at 4 weeks to up to 30% at 12 weeks in vivo); moreover, the cell-laden hydrogels did not trigger an immune response in vivo. Hence, our hydrogel formulation showed a favorable profile in terms of safety and biocompatibility, and it may be applied in tissue engineering strategies for cartilage and meniscus repair.

Long-Term Coronavirus Disease 2019 Complications in Inpatients and Outpatients: A One-Year Follow-up Cohort Study.

BACKGROUND: As the coronavirus pandemic spreads, more and more people are infected with severe acute respiratory syndrome coronavirus 2. The short- and medium-term effects of the infection have been described, but the description of the long-term sequelae is lacking in the literature. METHODS: Patients healed from coronavirus disease 2019 (COVID-19) from February 2020 to May 2020 were considered for inclusion in this study, regardless of the severity of the disease during the acute phase. Eligible patients were consecutively contacted and a semistructured interview was administered between February and March 2021 by trained medical staff. RESULTS: Three hundred three patients were eligible and accepted to participate in the study and were enrolled. Of those surveyed, most patients (81%) reported at least 1 symptom, and the most prevalent symptoms were fatigue (52%), pain (48%), and sleep disorders (47%). Sensory alterations were present in 28% of surveyed patients, but in most of these cases (74% of those affected by sensory alterations or 20% of the overall sample) symptoms reported were either anosmia or dysgeusia. Higher prevalence was generally observed with increasing age, although the most relevant differences were observed when comparing young versus middle-aged adults. CONCLUSIONS: At 12 months after acute infection, COVID-19 survivors were still suffering from symptoms identified at shorter follow-up, and the most frequent symptoms included fatigue, pain, and sleep disorders. A more severe impairment in the acute phase did not seem to predict more severe complications.

Bacterial adhesion on spinal implants: An in vitro study of "hot spots".

Few studies evaluated bacterial colonization of spinal implants from a "topographic" point of view. This lack of knowledge could hinder the development of more effective strategies in the prevention and treatment of postoperative spinal infections. The aim of this in vitro study was the analysis of the adhesion pattern of sessile cells on conventional spinal implants, to identify "hot spots" on implants where bacterial adhesion could be favored. Clinically relevant Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa isolates were grown on commercially available end product spinal implants. To identify sessile cells attached to implant surfaces, confocal laser scan microscopy was used. Different areas from the spinal instrumentations (both Ti and CoCr) were selected for biofilm quantification. Bacterial biofilm was markedly increased in the cut of the rods, both Ti and CoCr, as the uneven surface deriving from the cut might foster cell adhesion. Though not statistically significant, a difference was observed between the rod and the area of the notch, possibly as a consequence of the smoothening effect deriving from the bending of the rod. Finally, the amount of biofilm produced on cobalt-chromium surfaces was always more significant than that formed on titanium surfaces. This study highlights how bacterial adhesion through biofilm formation is favored on the surfaces of higher irregularity and that staphylococci are able to increase sessile biomass on CoCr surfaces. These preliminary results show how surface modifications on the implants may play a key role in bacterial adhesion, opening an exciting field for future research.

Management of Osteoarthritis During the COVID-19 Pandemic.

The pandemic spread of the new coronavirus disease 2019 (COVID-19) infection in China first, and all over the world at present, has become a global health emergency due to the rapidly increasing number of affected patients. Currently, a clear relationship between COVID-19 infection incidence and/or complications due to chronic or occasional treatments for other pathologies is still not clear, albeit the COVID-19 pandemic may condition the treatment strategy of complex disorders, such as osteoarthritis (OA). Importantly, OA is the most common age-related joint disease, affecting more than 80% of people older than the age of 55, an age burden also shared with the highest severity in COVID-19 patients. OA patients often show a large array of concomitant pathologies, such as diabetes, inflammation, and cardiovascular diseases that are again shared with COVID-19 patients and may therefore increase complications. Moreover, different OA treatments, such as NSAIDs, paracetamol, corticosteroids, opioids, or other molecules have a wide array of iatrogenic effects, potentially increasing COVID-19 secondary infection incidence or complications. In this review we critically analyze the evidence on either negative or positive effects of drugs commonly used to manage OA in this particular scenario. This would provide orthopedic surgeons in particular, and physicians, pharmacologists, and clinicians in general, a comprehensive description about the safety of the current pharmacological approaches and a decision-making tool to treat their OA patients as the coronavirus pandemic continues.

Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.

Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.

Osteochondral repair by a novel interconnecting collagen-hydroxyapatite substitute: a large-animal study.

A novel three-dimensional bicomponent substitute made of collagen type I and hydroxyapatite was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase. Thirty-six osteochondral lesions were created in the trochlea of six pigs; in each pig, two lesions were treated with scaffolds seeded with autologous chondrocytes (cell+group), two lesions were treated with unseeded scaffolds (cell- group), and the two remaining lesions were left untreated (untreated group). After 3 months, the animals were sacrificed and the newly formed tissue was analyzed to evaluate the degree of maturation. The International Cartilage Repair Society (ICRS) macroscopic assessment showed significantly higher scores in the cell- and untreated groups when compared with the cell+ group. Histological evaluation showed the presence of repaired tissue, with fibroblast-like and hyaline-like areas in all groups; however, with respect to the other groups, the cell- group showed significantly higher values in the ICRS II histological scores for "cell morphology" and for the "surface/superficial assessment." While the scaffold seeded with autologous chondrocytes promoted the formation of a reparative tissue with high cellularity but low glycosaminoglycans (GAG) production, on the contrary, the reparative tissue observed with the unseeded scaffold presented lower cellularity but higher and uniform GAG distribution. Finally, in the lesions treated with scaffolds, the immunohistochemical analysis showed the presence of collagen type II in the peripheral part of the defect, indicating tissue maturation due to the migration of local cells from the surroundings. This study showed that the novel osteochondral scaffold was easy to handle for surgical implantation and was stable within the site of lesion; at the end of the experimental time, all implants were well integrated with the surrounding tissue and no signs of synovitis were observed. The quality of the reparative tissue seemed to be superior for the lesions treated with the unseeded scaffolds, indicating the promising potential of this novel biomaterial for use in a one-stage procedure for osteochondral repair.

Collagen scaffold for cartilage tissue engineering: the benefit of fibrin glue and the proper culture time in an infant cartilage model.

This study (i) developed a scaffold made of collagen I designed for hosting the autologous chondrocytes, (ii) focused on the optimization of chondrocytes seeding by the addition of the fibrin glue, and (iii) investigated the culture time for the ideal scaffold maturation in vitro. In the first part of the study, fresh chondrocytes were isolated from infant swine articular cartilage, and immediately seeded onto the collagen sponges either in medium or in fibrinogen in order to show the contribute of fibrin glue in cell seeding and survival into the scaffold. In the second part of the study, chondrocytes were first expanded in vitro and then resuspended in fibrinogen, seeded in collagen sponges, and cultured for 1, 3, and 5 weeks in order to identify the optimal time for the rescue of cell phenotype and for the scaffold maturation into a tissue with chondral properties. The histological and immunohistochemical data from the first part of the study (study with primary chondrocytes) demonstrated that the presence of fibrin glue ameliorated cell distribution and survival into the chondral composites. The second part of this work (study with dedifferentiated chondrocytes) showed that the prolongation of the culture to 3 weeks promoted a significant restoration of the cell phenotype, resulting in a composite with proper morphological features, biochemical composition, and mechanical integrity. In conclusion, this study developed a collagenic-fibrin glue scaffold that was able to support chondrocyte survival and synthetic activity in a static culture; in particular, this model was able to turn the engineered samples into a tissue with chondral-like properties when cultured in vitro for at least 3 weeks.