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Background: The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in knee chondroplasty and osteoarthritis (OA); however, little evidence of its efficacy in hip OA exists. Purpose: To compare the therapeutic efficacy of autologous PRP, hyaluronic acid (HA), or a combination of both (PRP+HA) in hip OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients aged between 18 and 65 years who were treated with outpatient surgery and who had hip OA and pain intensity at baseline of >20 on a 100-mm visual analog scale (VAS) were recruited for this study. Exclusion criteria were extensive surgery; presence of excessive deformities; or rheumatic, infective, cardiovascular, or immune system disorders. The primary outcome measure was a change in pain intensity as assessed by the VAS at 2, 6, and 12 months after treatment. Secondary outcome measures were the Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and concentration of growth factors in PRP and their correlation with clinical outcomes. Clinical outcomes were evaluated by assessors and collectors blinded to the type of treatment administered. Results: A total of 111 patients were randomly assigned to 3 groups and received 3 weekly injections of either PRP (44 patients), PRP+HA (31 patients), or HA (36 patients). At all follow-ups, the PRP group had the lowest VAS scores. In particular, at 6-month follow-up, the mean VAS score was 21 (95% CI, 15-28) in the PRP group, 35 (95% CI, 26-45) in the PRP+HA group, and 44 (95% CI, 36-52) in the HA group ( P < .0005 [PRP vs HA] and P = .007 [PRP vs PRP+HA]; F = 0.663). The WOMAC score of the PRP group was significantly better at 2-month follow-up (mean, 73; 95% CI, 68-78) and 6-month follow-up (mean, 72; 95% CI, 67-76) but not at 12-month follow-up. A significant, “moderate” correlation was found between interleukin-10 and variations of the VAS score ( r = 0.392; P = .040). Significant improvements were achieved in reducing pain and ameliorating quality of life and functional recovery. Conclusion: Results indicated that intra-articular PRP injections offer a significant clinical improvement in patients with hip OA without relevant side effects. The benefit was significantly more stable up to 12 months as compared with the other tested treatments. The addition of PRP+HA did not lead to a significant improvement in pain symptoms.

Mesenchymal stem cells (MSCs) from bone marrow (BM) are widely used for bone and less for cartilage tissue regeneration due to their self-renewal and differentiating properties into osteogenic or chondrogenic lineages. This review considers the last decade of clinical trials involving a two-step procedure, by expanding in vitro MSCs from BM, or the so called "one-step" procedure, using BM in toto or BM concentrate, for the regeneration of cartilage and osteochondral tissue defects. The following conclusions were drawn: (1) Cartilage defects that can be repaired by the two-step technique are about twice the size as those where the one-step method is used; (2) the two-step procedure is especially used for the treatment of osteoarthritic lesions, whereas the one-step procedure is used for osteochondral defects; (3) the number of transplanted cells ranges between 3.8×10(6) and 11.2×10(6) cells/mL, and the period of cell culture expansion of implanted MSCs varies widely with regard to the two-step procedure; (4) hyaluronic or collagenic scaffolds are used in all the clinical studies analyzed for both techniques; (5) the follow-up of the two-step procedure is longer than that of the one-step method, despite having a lower number of patients; and, finally, (6) the mean age of the patients (about 39 years old) is similar in both procedures. Clinical results underline the safety and good and encouraging outcomes for the use of MSCs in clinics. Although more standardized procedures are required, the length of follow-up and the number of patients observed should be augmented, and the design of trials should be implemented to achieve evidence-based results.

From the observations, it is possible to demonstrate that Hyaff-11, a hyaluronan-based scaffold, has potential for MSC implantation and that may have application for the treatment of early OA in humans.

Purpose Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to other therapies. Methods After ultrasonographic localisation of the lesion, the autologous BMMNC suspension and PRP were injected directly into the core lesion. BMMNC and platelet count as well as growth factors in PRP were measured to determine factors influencing the clinical outcome. Results Horses showed a marked improvement in their degree of lameness and 84.6% were able to return to competition. Among all the factors studied, the platelet concentration predicted the healing time: significantly faster recovery (p= 0.049) was observed in cases of PRP with more than 750× 10 3 /μl platelets. Conclusions Competition horses are involved in highly demanding activities, thus being a similar model for the high mechanical overload typical of human athletes. The promising results obtained suggest that this combined biological approach may be useful even for the treatment of recalcitrant overuse musculoskeletal injuries in highly demanding patients if the appropriate dose of cells and GFs is applied.

The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided into three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes, and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At a 12-month gross assessment, histology and histomorphometry were used to assess the meniscus implant, knee joint, and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. The implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those underwent meniscectomy (p<0.0005), and the Osteoarthritis Research Society International score showed that osteoarthritic changes were significantly less in the cell-seeded group than in the meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated. Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology.

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