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Acute or degenerative meniscus tears are the most common knee lesions. Meniscectomy provides symptomatic relief and functional recovery only in the short- to mid-term follow-up but significantly increases the risk of osteoarthritis. For this reason, preserving the meniscus is key, although it remains a challenge. Allograft transplants present many disadvantages, so during the last 20 years preclinical and clinical research focused on developing and investigating meniscal scaffolds. The aim of this systematic review was to collect and evaluate all the available evidence on biosynthetic scaffolds for meniscus regeneration both in vivo and in clinical studies. Three databases were searched: 46 in vivo preclinical studies and 30 clinical ones were found. Sixteen natural, 15 synthetic, and 15 hybrid scaffolds were studied in vivo. Among them, only 2 were translated into clinic: the Collagen Meniscus Implant, used in 11 studies, and the polyurethane-based scaffold Actifit®, applied in 19 studies. Although positive outcomes were described in the short- to mid-term, the number of concurrent procedures and the lack of randomized trials are the major limitations of the available clinical literature. Few in vivo studies also combined the use of cells or growth factors, but these augmentation strategies have not been applied in the clinical practice yet. Current solutions offer a significant but incomplete clinical improvement, and the regeneration potential is still unsatisfactory. Building upon the overall positive results of these “old” technologies to address partial meniscal loss, further innovation is urgently needed in this field to provide patients better joint sparing treatment options., Graphical abstract Image 1, Highlights • Animal studies employed natural, synthetic and hybrid natural/synthetic scaffolds. • Only in a few animal studies scaffold augmentation with cells or GFs was tested. • Only two meniscal scaffolds have reached clinical application: CMI and Actifit. • Clinical results are promising, but complete meniscus regeneration has not been achieved. • There is urgent need for technological innovation in the field of meniscal regeneration.

A systematic review of clinical applications of MSCs in the treatment of knee osteoarthritis (OA). Twenty-three papers were included in the final analysis (10 on BMAC and 13 on SVF). Of these, only 4 were randomised controlled trials (RCTs). The Coleman Score, used for bias risk evaluation, revealed an overall poor quality of the studies. In terms of clinical application, despite the apparent safety and the short-term positive clinical outcomes, clinicians reported different preparation and administration methods. The available literature is not sufficient to make any recommendation on the use of either product in clinical practice, even though they have both shown to be safe and have some short-term beneficial effects.

Purpose: To assess the return to sport rate of young professional athletes, to analyze their careers in terms of matches played and league participation over a minimum period of 6years after Meniscal Allograft Transplantation (MAT), as well as to assess the long-term clinical subjective outcomes and satisfaction. Methods: Thirteen professional athletes (ten soccer and one basketball players, one fencer and one wrestler) with a mean age at surgery of 23.4 ± 4.0 underwent MAT (six medial, seven lateral). The time required to return to sport, post-operative performance level and the number of reoperations were evaluated. At an average follow-up of 9.0 ± 2.8years, Lysholm, KOOS and Cincinnati scores were administered and collected. Results: Thirteen patients (100%) returned to sports practice after an average period of 11.8 ± 3.8months. Nine athletes (69%) returned to sports at the same pre-injury level. Overall, 93%, 85%, 62% and 55% were active until the 3rd, the 5th, the 7th and the 9th season after MAT, respectively. Seven patients (54%) underwent a reoperation after MAT, where only two of them (15%) were related to graft problems (one meniscectomy and one graft suture). Of the ten athletes that completed subjective evaluation, the mean Lysholm score was 72 ± 15 (0% “Excellent”, 10% “Good”, 60% “Fair”, 30% “Poor”). Of the athletes with lower scores, one suffered from patellar tendon rupture, one from post-operative infection and one from a previous femoral fracture. The mean Cincinnati knee score was 77 ± 18, while the average KOOS values were 60 ± 34 for sports. Conclusion: Meniscal Allograft Transplantation (MAT) in young professional athletes involved in strenuous activities allowed all patients to return to pre-injury sport and in nearly 70% of cases at their pre-injury level. After five seasons following MAT, 85% of patients were still active or playing more than 20–30 matches per season. On the other hand, nearly 50% underwent at least one reoperation and only 70% of patients were rated as “Good”, or “Fair” using the Lysholm score. Level of evidence: IV.

This article analyzes the current literature on the use of adipose-derived stem cells (ASCs) to evaluate the available evidence regarding their therapeutic potential in the treatment of cartilage pathology. Seventeen articles were included and analyzed, showing that there is overall a lack of high quality evidence concerning the use of ASCs. Most trials are case series with short-term evaluation. The most adopted approach consists of an intra-articular injection of the stromal vascular fraction (SVF) rather than the expanded cells. Based on the available data, no specific preparation method or formulation could be considered as the preferred choice in clinical practice.

Osteoarthritis (OA) is one of the most common causes of chronic disability in adults due to pain and altered joint function. Although most patients report pain and functional limitation, symptoms, age of onset and disease progression are extremely variable. While inflammation could play a central role in the OA pathogenesis and progression, many underpinning mechanisms are still unclear. A number of proinflammatory mediators have been found in OA joints and could play a role, such as IL-1, IL-6, IL-7, IL-8, IL-15, IL-17, IL-18, TNF-alpha, macrophage chemotactic protein (MCP)-1, interferon-induced protein (IP)-10, monokine induced by interferon (MIG), oncostatin M (OSM), growth-related oncogene (GRO)-alpha, chemokine (C-C-motif) ligand 19 (CCL19), macrophage inflammatory protein (MIP)-1beta, and TGF-alpha. Biological approaches have recently got increasing interest due to their anti-inflammatory and immunomodulatory properties, regenerative potential, and high tolerability. The primary aim of this paper is to report the current concepts on regenerative medicine for knee OA with a particular focus on Autologous Protein solution (APS). APS is a blood derived product obtained by using a proprietary device, made of APS Separator, which isolates WBCs and platelets in a small volume of plasma, and APS Concentrator, which further concentrates platelets, WBCs and plasma proteins. The result is a peculiar formulation differing from other biologic products as it contains high levels of growth factors (EGF, IGF-1, PDGF-AB, PDGF-BB, VEGF, TGF-β1) along with high concentrations of anti-inflammatory mediators (IL-1ra, sIL-1RII, sTNF-RI, sTNF-RII) and low levels of pro-inflammatory cytokines (Il-1β and TNF-α). While emerging evidence supports the use of APS, as confirmed by in vitro studies and preliminary clinical results, the real clinical potential of APS and its benefits are still under investigation.

Background. The use of laboratory-expanded mesenchymal stem cells (MSCs) is subject to several restrictions, resulting in “minimal manipulation” methods becoming the current most popular strategy to increase the use of MSCs in an orthopaedic practice. The aim of the present systematic review is to assess the clinical applications of “minimally” manipulated MSCs, either as bone marrow aspirate concentrate (BMAC) or as stromal vascular fraction (SVF), in the treatment of knee osteoarthritis (OA). Methods. A systematic review of three databases (PubMed, ScienceDirect, and Google Scholar) was performed using the following keywords: “Knee Osteoarthritis” with “(Bone marrow aspirate) OR (bone marrow concentrate)” or with “(adipose-derived mesenchymal stem cells) OR (adipose derived stromal cells) OR (stromal vascular fraction) OR (SVF)” as either keywords or MeSH terms. The reference lists of all retrieved articles were further reviewed for identification of potentially relevant studies. Results. Twenty-three papers were included in the final analysis (10 on BMAC and 13 on SVF). Of these, only 4 were randomized controlled trials (RCTs). Bias risk evaluation, performed using a modified Coleman score, revealed an overall poor quality of the studies. In terms of clinical application, despite the apparent safety of minimally manipulated MSCs and the short-term positive clinical outcomes associated with their use, clinicians reported different preparation and administration methods, ranging from single intra-articular injections to intraosseous applications to administration in combination with other surgical procedures. Conclusions. The available literature is undermined by both the lack of high-quality studies and the varied clinical settings and different protocols reported in the few RCTs presently published. This prevents any recommendation on the use of either product in a clinical practice. Nevertheless, the use of minimally manipulated MSCs (in the form of BMAC or SVF) has been shown to be safe and have some short-term beneficial effects.

In occidental societies, a great number of people practice sport regularly at all ages. In this context, cartilage injury incidences have become higher and higher. They are frequently diagnosed during knee arthroscopy even in asymptomatic patients. However, patients commonly present with pain, recurrent effusion, and loss of function. Concomitantly with the increasing incidence, the expectations of patients about function restore have risen as well. Since articular cartilage is characterized by a poor intrinsic regenerative capacity, treatment of these lesions is particularly challenging.

Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/β catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigated within innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods. A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-β catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-β catenin pathway in the OA setting. Results. Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/β-catenin signalling. Conclusions. While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/β catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies.