Profound Properties of Protein-Rich, Platelet-Rich Plasma Matrices as Novel, Multi-Purpose Biological Platforms in Tissue Repair, Regeneration, and Wound Healing.

Autologous platelet-rich plasma (PRP) preparations are prepared at the point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate), and variable leukocyte bioformulation and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and, ultimately, functional and structural repair. Normally, after PRP preparation, the PPP fraction is discarded. One of the less well-known but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside of the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation and fibrosis, and they promote keratinocyte migration and support tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating, in a fast and efficient manner, plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein-rich, platelet-rich plasma (PR-PRP) biological preparation. After the activation of proteins, mainly fibrinogen, the PR-PRP matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), as well as the embedded concentrated PRP cells and molecules. The administered PR-PRP biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PR-PRP matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of the PR-PRP matrix.

Preliminary osteogenic and antibacterial investigations of wood derived antibiotic-loaded bone substitute for the treatment of infected bone defects.

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection. Methods: Using an "in vitro 3D bone fracture model" to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated. Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation. Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.

Subchondral bone: An emerging target for the treatment of articular surface lesions of the knee.

Purpose: When dealing with the health status of the knee articular surface, the entire osteochondral unit has gained increasing attention, and in particular the subchondral bone, which plays a key role in the integrity of the osteochondral unit. The aim of this article was to discuss the current evidence on the role of the subchondral bone. Methods: Experts from different geographical regions were involved in performing a review on highly discussed topics about the subchondral bone, ranging from its etiopathogenetic role in joint degeneration processes to its prognostic role in chondral and osteochondral defects, up to treatment strategies to address both the subchondral bone and the articular surface. Discussion: Subchondral bone has a central role both from an aetiologic point of view and as a diagnostic tool, and its status was found to be relevant also as a prognostic factor in the follow-up of chondral treatment. Finally, the recognition of its importance in the natural history of these lesions led to consider subchondral bone as a treatment target, with the development of osteochondral scaffolds and procedures to specifically address osteochondral lesions. Conclusion: Subchondral bone plays a central role in articular surface lesions from different points of view. Several aspects still need to be understood, but a growing interest in subchondral bone is to be expected in the upcoming future towards the optimization of joint preservation strategies. Level of Evidence: Level V, expert opinion.

Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

Conservative Treatment for Ankle Cartilage: Cellular and Acellular Therapies: A Systematic Review.

Biological agents like growth factors (ie, platelet rich plasma) and mesenchymal stem cells are rising in popularity among orthopedics. Orthobiologics therapy aims to fill the gap between conventional conservative therapies like hyaluronic acid and surgery, especially for cartilage disease. Ankle cartilage defects are very symptomatic and could lead to a severe decrease of quality of life in patients, because of pain, swelling, and inability to walk without pain. In this scenario, this paper aims to systematically review the current literature available about biological therapies for ankle cartilage.

The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1-Blood-derived products (platelet-rich plasma).

PURPOSE: The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decision-making and administration-related aspects when using blood-derived orthobiologics (for simplicity indicated as PRP-platelet-rich plasma-with PRP being the most common product) for the management of knee osteoarthritis (OA). METHODS: Leading European expert clinicians and scientists were divided into a steering group, a rating group and a peer review group. The steering group prepared 28 question-statement sets divided into three sections: PRP rationale and indications, PRP preparation and characterisation and PRP protocol. The quality of the statements received grades of recommendation ranging from A (high-level scientific support) to B (scientific presumption), C (low-level scientific support) or D (expert opinion). The question-statement sets were then evaluated by the rating group, and the statements scored from 1 to 9 based on their degree of agreement with the statements produced by the steering group. Once a general consensus was reached between the steering and rating groups, the document was submitted to the peer review group who evaluated the geographic adaptability and approved the document. A final combined meeting of all the members of the consensus was held to produce the official document. RESULTS: The literature review on the use of blood-derived products for knee OA revealed that 9 of 28 questions/statements had the support of high-level scientific literature, while the other 19 were supported by a medium-low scientific quality. Three of the 28 recommendations were grade A recommendations: (1) There is enough preclinical and clinical evidence to support the use of PRP in knee OA. This recommendation was considered appropriate with a strong agreement (mean: 8). (2) Clinical evidence has shown the effectiveness of PRP in patients for mild to moderate degrees of knee OA (KL ≤ 3). This recommendation was considered appropriate with a strong agreement (mean: 8.1). (3) PRP injections have been shown to provide a longer effect in comparison to the short-term effect of CS injections. They also seem to provide a safer use profile with less potential related complications. This recommendation was considered appropriate with a very strong agreement (mean: 8.7). Six statements were grade B recommendations, 7 were grade C and 12 were grade D. The mean rating score was 8.2 ± 0.3. CONCLUSIONS: The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1-3. LEVEL OF EVIDENCE: Level II.

An Innovative Topical Medical Device with Hyaluronic Acid and Polypeptides in Patients with Reduced Knee Function.

A topical medical device, AI500®, constituted of a single-chain polypeptide embedded in hyaluronic acid, was tested and evaluated in patients with reduced knee function due to osteoarthritis and other knee conditions. A total of 35 participants with reduced knee function assessed by the WOMAC Physical Function score were recruited. Four study visits were planned, from the first application at V0 to 1 week follow up at V3. Patient symptomatology was evaluated after 24 h (V1) and after 48 h (V2) through phone contact, and after 1 week from V0, on site (V3). The overall duration of the follow up was one week. An amelioration of 40% in WOMAC Physical Functional scores after 1 week of treatment was recorded, thus achieving the primary endpoint of 20%. Furthermore, a reduction of 29% in Physical Functional scores and of 28% in total WOMAC scores between V0-V2 was registered, together with a decrease of 39% between V0 and V3. The NRS scale showed a 29% and 37% reduction in pain between V0-V1 and V0-V2, respectively. Product safety was confirmed by the very low rate of adverse effects, non-device related, observed in only 2 patients out of 35, resolved spontaneously within 24-48 h. No safety concerns or risks associated with the use of the device were highlighted. There are few the studies on the topical use of HA-based gels for the treatment of knee problems. Compared to invasive intra-articular injections and oral pharmacological therapies used in cases of knee pain, the topical application of AI500® is non-invasive, safe, and appreciated by patients. Good results in terms of functional improvement and symptoms resolution were obtained in less than 1 week.

Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

INTRODUCTION: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. METHODS: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. RESULTS: Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. CONCLUSIONS: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

Using Three-Dimensional Printing Technology to Solve Complex Primary Total Hip Arthroplasty Cases: Do We Really Need Custom-Made Guides and Templates? A Critical Systematic Review on the Available Evidence.

The burden of osteoarthritis (OA) is around 300 million people affected worldwide, with the hip representing a commonly affected joint. Total hip arthroplasty (THA) has been used with notable success as a definitive treatment to improve pain and function in hip OA patients. The recent advent of new technologies, such as 3D printing, has pushed the application of these new concepts toward applications for the well-known THA. Currently, the evidence on the use of 3D printing to aid complex primary THA cases is still scarce. METHODS: An extensive literature review was conducted to retrieve all articles centered on the use of 3D printing in the setting of primary THA. RESULTS: A total of seven studies were included in the present systematic review. Four studies investigated the use of 3D-printed surgical guides to be used during surgery. The remaining three studies investigated the benefit of the use of 3D-printed templates of the pelvis to simulate the surgery. CONCLUSIONS: The use of 3D printing could be a promising aid to solve difficult primary total hip arthroplasty cases. However, the general enthusiasm in the field is not supported by high-quality studies, hence preventing us from currently recommending its application in everyday practice.

Synthetic peptides of IL-1Ra and HSP70 have anti-inflammatory activity on human primary monocytes and macrophages: Potential treatments for inflammatory diseases.

Chronic inflammatory diseases are increasing in developed societies, thus new anti-inflammatory approaches are needed in the clinic. Synthetic peptides complexes can be designed to mimic the activity of anti-inflammatory mediators, in order to alleviate inflammation. Here, we evaluated the anti-inflammatory efficacy of tethered peptides mimicking the interleukin-1 receptor antagonist (IL-1Ra) and the heat-shock protein 70 (HSP70). We tested their biocompatibility and anti-inflammatory activity in vitro in primary human monocytes and differentiated macrophages activated with two different stimuli: the TLR agonists (LPS + IFN-γ) or Pam3CSK4. Our results demonstrate that IL-1Ra and HSP70 synthetic peptides present a satisfactory biocompatible profile and significantly inhibit the secretion of several pro-inflammatory cytokines (IL-6, IL-8, IL-1ß and TNFα). We further confirmed their anti-inflammatory activity when peptides were coated on a biocompatible material commonly employed in surgical implants. Overall, our findings support the potential use of IL-1Ra and HSP70 synthetic peptides for the treatment of inflammatory conditions.

An in vitro model for osteoarthritis using long-cultured inflammatory human macrophages repeatedly stimulated with TLR agonists.

Osteoarthritis (OA) is characterized by an abundance of inflammatory M1-like macrophages damaging local tissues. The search for new potential drugs for OA suffers from the lack of appropriate methods of long-lasting inflammation. Here we developed and characterized an in vitro protocol of long-lasting culture of primary human monocyte-derived macrophages differentiated with a combination of M-CSF+GM-CSF that optimally supported long-cultured macrophages (LC-Mϕs) for up to 15 days, unlike their single use. Macrophages repeatedly stimulated for 15 days with the TLR2 ligand Pam3CSK4 (LCS-Mϕs), showed sustained levels over time of IL-6, CCL2, and CXCL8, inflammatory mediators that were also detected in the synovial fluids of OA patients. Furthermore, macrophages isolated from the synovia of two OA patients showed an expression profile of inflammation-related genes similar to that of LCS-Mϕs, validating our protocol as a model of chronically activated inflammatory macrophages. Next, to confirm that these LCS-Mϕs could be modulated by anti-inflammatory compounds, we employed dexamethasone and/or celecoxib, two drugs widely used in OA treatment, that significantly inhibited the production of inflammatory mediators. This easy-to-use in vitro protocol of long-lasting inflammation with primary human macrophages could be useful for the screening of new compounds to improve the therapy of inflammatory disorders.

Early application of extracorporeal shock wave therapy improves pain control and functional scores in patients undergoing total knee arthroplasty: a randomized controlled trial.

PURPOSE: The use of biophysical stimuli produced by extracorporeal shock wave therapy (ESWT) can improve the rehabilitation treatment of patients undergoing total knee arthroplasty (TKA). The aim of our study is to evaluate the short-term efficacy of early postoperative ESWT in combination with physiotherapy in terms of pain reduction and motor function recovery of patients undergoing TKA and compare it with conventional physiotherapy treatment. METHODS: Fifty-six patients undergoing TKA were enrolled in the study from January 2019 to February 2020. Patients received two sessions of physiotherapy daily, with (experimental group) or without (control group) four sessions of ESWT within seven days after surgery. Patients were prospectively evaluated at baseline and at post-operative day two and seven. Assessment included active knee range of motion (aROM), timed up and go (TUG) test, visual analogue scale (VAS) for pain, and Borg scale. RESULTS: Fifty patients completed the study. Both treatments proved to be effective in reducing pain and improving the knee range of motion and functional scores at seven days after surgery: the aROM in the ESWT group was 36.8 ± 11.0 grades (p < 0.001), while in control group was 19.8 ± 7.8 grades (p < 0.001). TUG, VAS, and BORG scores showed a similar trend. Comparative analysis revealed superior clinical results for the experimental group in all the outcomes, in particular aROM (96.0 ± 5.40 vs. 81.20 ± 11.01, p < 0.001) and TUG test (17.4 ± 5.61 vs. 21.24 ± 5.88, p < 0.001), at day seven after surgery. CONCLUSION: Early application of ESWT in addition to physiotherapy can positively influence the rehabilitation process after TKA. The treatment proved to be well tolerated and safe. Preliminary results demonstrated better pain control and functional scores compared to physiotherapy alone.

Placenta-Derived Products Demonstrate Good Safety Profile and Overall Satisfactory Outcomes for Treating Knee Osteoarthritis: A Systematic Review of Clinical Evidence.

PURPOSE: To summarize the available evidence regarding the clinical application of placenta-derived products to treat knee osteoarthritis (OA), underlining the differences existing among products, their preparation methods, and the clinical results reported so far. METHODS: A research on PubMed, Cochrane, and Google Scholar databases was performed. The following inclusion criteria for relevant articles were used: (1) randomized controlled trials (RCTs), prospective and retrospective studies, on humans; (2) written in English; (3) published in indexed journals in the last 10 years (2011-2022); and (4) dealing with the use of placenta-derived products for the treatment of knee OA. Exclusion criteria were articles written in other languages; animals or in vitro trials; reviews; and trials analyzing other applications of placenta-derived products not related to knee OA. RESULTS: In total, 16 studies were included in the present systematic review. Five studies investigated placenta-derived products as an augmentation during surgical procedures, whereas 11 studies were focused on the injective approach only. Of these, only 4 were RCTs and were all from the injective approach group. Potential risk of bias was carried out using Cochrane Risk of Bias 2 tool for RCTs and a modified Coleman approach for nonrandomized studies, revealing for both an overall insufficient quality. Clinical outcomes reveal excellent safety profile and notable efficacy, despite the different types of products used and different administration methods adopted. CONCLUSIONS: Placental products showed a good safety profile and overall satisfactory outcomes for the treatment of knee OA. LEVEL OF EVIDENCE: Level IV, systematic review of Level II, III and IV studies.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

AIMS: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. MATERIALS AND METHODS: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. RESULTS: NInject was cost-effective compared to microfracture (ICER: £5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of £20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: £69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. LIMITATIONS AND CONCLUSION: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

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.

Bone marrow aspirate concentrate quality is affected by age and harvest site.

PURPOSE: To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages. METHODS: BMAC was obtained from two groups of patients based on age (n = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression. RESULTS: Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 107) compared to older patients (1.2 ± 0.8 × 107) (p < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 107, p < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p = 0.006). CONCLUSION: Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.

Chitosan based scaffold applied in patellar cartilage lesions showed positive clinical and MRI results at minimum 2 years of follow up.

PURPOSE: New scaffold-based cartilage regeneration techniques have been developed to improve the results of microfractures also in complex locations like the patello-femoral joint. The aim of this study was to analyse the results obtained in patellar lesions treated with a bioscaffold,  a mixture composed by a chitosan solution, a buffer, and the patient's whole blood  which forms a stable clot into the lesion. METHODS: Fifteen patients with ICRS grade 3-4 cartilage lesions of the patellar surface were treated with a chitosan bioscaffold. Fourteen patients were clinically and radiologically evaluated prospectively for a minimum follow-up of 2 years with IKDC, KOOS, Tegner score, and MRI. The mean age of patients at the time of surgery was 31.8 ± 11.9 and nine patients presented degenerative aetiology, four patients with previous trauma, and 1 patient with osteochondritis dissecans.  RESULTS: The IKDC subjective score improved from 46.2 ± 19.3 preoperatively to 69.5 ± 20.3 (p < 0.05) and 74.1 ± 23.2 (p < 0.05) at 12 and 24 months, respectively. Also KOOS Pain, KOOS Sport/Rec and KOOS QOL showed a significant improvement from baseline to 12 months and to the final follow-up. MRI evaluation showed a complete filling of the cartilage defect at the final follow-up in 70% of the lesions, obtaining a total MOCART 2.0 score of 71.5 ± 13.6 at 24 months after surgery. CONCLUSION: Chondral patellar lesions represent a complex pathology, with lower results compared to other sites. This bioscaffold represents a safe surgical treatment providing a significant clinical improvement at 24 months in the treatment of patellar cartilage lesions. LEVEL OF EVIDENCE: IV.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Conservative vs. Surgical Management for Femoro-Acetabular Impingement: A Systematic Review of Clinical Evidence.

Femoro-acetabular impingement (FAI) syndrome is one of the most studied conditions in sports medicine. Surgical or conservative approaches can be proposed for treating FAI, although the best standard of care is not established yet. Our aim is to provide a comprehensive review of the best treatment for FAI syndrome evaluating differences in outcomes between surgical and non-operative management. A literature search was carried out on the PubMed, EMBASE, Scopus, and PEDro databases, using the following keywords: "femoroacetabular impingement", "FAI", in association with "surgery", "arthroscopy", "surgical" and "conservative", "physiotherapy", "physical therapy", "rehabilitation", "exercise". Only Level I RCTs were included. Four articles were selected for this systematic review. Our analysis showed different therapeutic protocols, follow-up periods, and outcomes; however, three out of the four studies included favored surgery. Our study demonstrates beneficial effects for both arthroscopic treatment and a proper regimen of physical therapy, nevertheless a surgical approach seemed to offer superior short-term results when compared to conservative care only. Further trials with larger sample sizes and longer follow-ups are needed to assess the definitive approach to the FAI condition.