Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl₂, 10% of autologous thrombin, 10% of a mixture of CaCl₂+ thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl₂, thrombin, and CaCl₂/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl₂/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl₂induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Introduction: Cell 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. Methods: The 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. Results: Labeled-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. Conclusions: Our 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.

There has been considerable advancement over the last few years in the treatment of osteoarthritis, common chronic disease and a major cause of disability in older adults. In this pathology, the entire joint is involved and the regeneration of articular cartilage still remains one of the main challenges, particularly in an actively inflammatory environment. The recent strategies for osteoarthritis treatment are based on the use of different therapeutic solutions such as cell and gene therapies and tissue engineering. In this review, we provide an overview of current regenerative strategies highlighting the pros and cons, challenges and opportunities, and we try to identify areas where future work should be focused in order to advance this field.

Elbow stiffness is a common complication after elbow trauma. The elbow capsule is often thickened, fibrotic, and contracted at the time of surgical release. The limited studies available suggest that the capsule is contracted because of fibroblast-to-myofibroblast differentiation. We hypothesize that myofibroblasts are absent in normal elbow capsules and in acute trauma and that they are subsequently elevated in patients with posttraumatic elbow contracture. We obtained twenty-one human elbow joint capsules within fourteen days after an elbow fracture and/or dislocation and thirty-four elbow joint capsules in thirty-four patients who had undergone operative release of posttraumatic contractures more than five months after injury. Myofibroblasts in the joint capsules were quantified with use of immunohistochemistry. Alpha-smooth muscle actin was used as a marker for myofibroblasts. Samples were characterized and were scored by an independent pathologist blinded for clinical data. Eleven capsules were associated with the acute phase after trauma (hours to less than seven days), and staining for alpha-smooth muscle actin was negative in all but one capsule. Ten capsules were associated with a later posttraumatic phase with myofibroblasts staining positive for alpha-smooth muscle actin in all but two capsules. Thirty-two long-standing contractures showed a histological pattern consistent with chronic stages of fibrosis, characterized by increased fibroblast-like cell proliferation and higher cellular density of fibroblast-like cells with highly unstructured collagen. Two joint capsules showed an earlier phase of fibrosis. Only two of the long-standing contractures had staining of alpha-smooth muscle actin in fibroblast-like cells; the lack of staining in the other contractures suggested an absence of myofibroblasts. This study presents negative results on the hypothesis that myofibroblast numbers are elevated in long-standing (more than five months) human posttraumatic elbow capsules. The absence of myofibroblasts in long-standing elbow contracture capsules is in contrast to most other studies on human tissue in the literature to date.