IntroductionCell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model.MethodsThe induction of OA was performed surgically through bilateral anterior cruciate ligament transection (ACLT) to achieve eight weeks from ACLT a mild grade of OA. A total of 2 × 106 and 6 × 106 autologous ASCs isolated from inguinal fat, expanded in vitro and suspended in 4% rabbit serum albumin (RSA) were delivered in the hind limbs; 4% RSA was used as the control. Local bio-distribution of the cells was verified by injecting chloro-methyl-benzamido-1,1'-dioctadecyl-3,3,3'3'-tetra-methyl-indo-carbocyanine per-chlorate (CM-Dil) labeled ASCs in the hind limbs. Cartilage and synovial histological sections were scored by Laverty's scoring system to assess the severity of the pathology. Protein expression of some extracellular matrix molecules (collagen I and II), catabolic (metalloproteinase-1 and -3) and inflammatory (tumor necrosis factor- α) markers were detected by immunohistochemistry. Assessments were carried out at 16 and 24 weeks.ResultsLabeled-ASCs were detected unexpectedly in the synovial membrane and medial meniscus but not in cartilage tissue at 3 and 20 days from ASC-treatment. Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.ConclusionsOur data reveal a healing capacity of ASCs in promoting cartilage and menisci repair and attenuating inflammatory events in synovial membrane inhibiting OA progression. On the basis of the local bio-distribution findings, the benefits obtained by ASC treatment could be due to a trophic mechanism of action by the release of growth factors and cytokines.

Whilst the entire world is battling the second wave of COVID-19, a substantial proportion of patients who have suffered from the condition in the past months are reporting symptoms that last for months after recovery, i. e., long-term COVID-19 symptoms. We aimed to assess the current evidence on the long-term symptoms in COVID-19 patients. We did a systematic review on PubMed, Web of Science, EMBASE, and Google Scholar from database inception to February 15, 2021, for studies on long-term COVID-19 symptoms. We included all type of papers that reported at least one long-term COVID-19 symptom. We screened studies using a standardized data collection form and pooled data from published studies. Cohort cross-sectional, case-report, cases-series, case-control studies, and review were graded using specific quality assessment tools. Of 11,361 publications found following our initial search we assessed 218 full-text articles, of which 145 met all selection criteria. We found that 20.70% of reports on long-term COVID-19 symptoms were on abnormal lung functions, 24.13% on neurologic complaints and olfactory dysfunctions, and 55.17% on specific widespread symptoms, mainly chronic fatigue, and pain. Despite the relatively high heterogeneity of the reviewed studies, our findings highlighted that a noteworthy proportion of patients who have suffered from SARS-CoV-2 infection present a “post-COVID syndrome.” The multifaceted understanding of all aspects of the COVID-19 pandemic, including these long-term symptoms, will allow us to respond to all the global health challenges, thus paving the way to a stronger public health.

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Effects of pulsed electromagnetic fields (PEMFs, 75 Hz, 1.6 mT) were investigated in 12 rabbits after placing hydroxyapatite (HA) implants in their femoral condyles. Six animals were stimulated with PEMFs for three consecutive weeks, 6 h/day, while the remaining animals were sham-treated (Control Group). Rabbits were sacrificed at 3 and 6 weeks (after a 3-week non-stimulation period) for histomorphometric analysis and microhardness testing (at 200, 500, 1000, 2000 pm from the implant) around the implants. Histomorphometric analysis did not highlight any significant changes. On the contrary, there were statistically significant differences between the effects produced by PEMFs and Control Groups ( F = 149.70, p < 0.0005) on the Affinity Index results, as well as by the experimental time of 6 and 3 weeks ( F = 17.12, p = 0.001) on the same results. In PEMF-stimulated animals the microhardness (HV) values measured in trabecular bone at a distance of 200 and 500 pm from the implants, were significaiitly higher with respect to controls. At 6 weeks, HV values at the bone-implant interface in PEMF-stimulated animals were not significantly different with respect to normal bone, while they remained significantly lower in control animals. Both morphological and structural results demonstrated a positive therapeutic effect of PEMFs in accelerating HA osteointegration in trabecular bone.

Maxillofacial, orthopedic, oral, and plastic surgery require materials for tissue augmentation, guided regeneration, and tissue engineering approaches. In this study, the aim was to develop and characterize a new extrudable hydrogel, based on agarose gel (AG; 1.5% wt) and to evaluate the local effects after subcutaneous implantation in comparison with collagen and hyaluronic acid. AG chemical-physical properties were ascertained through Fourier transform infrared (FT-IR) spectroscopy and rheological analysis. In vivo subcutaneous implants were performed, and histological and histomorphometric evaluations were done at 1, 4, 12, and 16 weeks. FT-IR confirmed that spectroscopic properties were the same for the baseline agarose and rheological characterization established that AG is a weak hydrogel. Subcutaneous AG implants induced new vessels and fibrous tissue formation rich in neutrophils; the capsule thickness around AG increased until the 12th week but remained thinner than those around hyaluronic acid and collagen. At 16 weeks, the thickness of the capsule significantly decreased around all materials. This study confirmed that 1.5% wt AG possesses some of the most important features of the ideal biocompatible material: safety, effectiveness, costless, and easily obtained with specific chemical and geometrical characters; the AG can represent a finely controllable and biodegradable polymeric system for cells and drug delivery applications.

Extracorporeal shock wave therapy has been used increasingly in musculoskeletal disorders although its biologic mechanisms are not understood completely. The current study evaluated the effects of extracorporeal shock wave therapy on human osteoblastlike cells by using an electrohydraulic shock wave generator and comparing three energy levels. (Group A, 14 kV and 0.15 mJ/mm2; Group B, 21 kV and 0.31 mJ/mm2; Group C, 28 kV and 0.40 mJ/mm2; Control Group, no energy) and two total impulses (500, 1000) for each level. At the end of treatment, a reduction by approximately 76% was observed in Group C cell number versus basal value when compared with the other groups. Viability, biochemical activity, and gene expression of cultured cells were evaluated 24 and 48 hours after treatment. The viability test showed a decrease in Group C viability of approximately 54% at both culture times as compared with the other groups. Significant increases in nitric oxide, osteocalcin, and transforming growth factor-beta1 production ranging from 10% to 35% were found in Group A. All treated groups had lower C-terminal procollagen Type I values than the Control Group, but important increases were observed between 24 and 48 hours in all groups except Group C. This particular finding reveals that osteoblast differentiation in Group A is enhanced strongly during the first 24 hours after exposure leading after another 24 hours to an increase in C-terminal procollagen Type I production and consequently in bone matrix deposition. The current study showed that one of the most important aspects to be considered is not the total number of impulses used, but the energy level of the shock waves, therefore confirming that extracorporeal shock wave therapy has a dose-dependent initial destructive effect on cells when the selected energy is higher than 21 kV.

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Frailty is a condition characterized by a high vulnerability to low-power stressor. Frailty increases with age and is associated with higher complications and mortality. Several indexes have been used to quantify frailty. Spine diseases, both degenerative and oncologic, frequently require surgery which is related to complications and mortality. Aim of the present systematic review was to collect the most frequently used frailty indexes in clinics to predict surgical outcomes in patients affected by spine diseases, taking into account gender differences. Three databases were employed, and 29 retrospective clinical studies were included in this systematic review. The identified spine pathologies were primary and metastatic spine tumors, adult spine deformity (ASD), degenerative spine disease (DSD), cervical deformity (CD) and other pathologies that affected lumbar spine or multiple spine levels. Eleven indexes were identified: modified Frailty Index (mFI), Adult spinal deformity frailty index (ASD-FI), mFI-5, Metastatic Spinal Tumor Frailty Index (MSTFI), Fried criteria, Cervical deformity frailty index (CD-FI), Spinal tumor frailty index (STFI), Frailty Phenotype criteria (FP), Frailty Index (FI), FRAIL scale and Modified CD-FI (mCD-FI). All these indexes correlated well with minor and major postoperative complications, mortality and length of stay in hospital. Results on gender differences and frailty are still conflicting, although few studies show that women are more likely to develop frailty and more complications in the post-operative period than men. This systematic review could help the surgeon in the adoption of frailty indexes, before the operation, and in preventing complications in frail patients.