The Dual-Responsive Interaction of Particulated Hyaline Cartilage and Plasma Rich in Growth Factors (PRGF) in the Repair of Cartilage Defects: An In Vitro Study.

The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy.

Particulated Autologous Chondral-Platelet-Rich Plasma Matrix Implantation (PACI) for Treatment of Full-Thickness Cartilage Osteochondral Defects.

Articular hyaline cartilage injuries can occur as a result of either traumatic of progressive degeneration. When the articular cartilage in a joint is damaged, it can cause joint pain and dysfunction, predisposing patients for the development of early-onset osteoarthritis. There are many restoration procedures available to treat these injuries, such as bone marrow-stimulation techniques, osteoarticular auto/allograft transplants, and autologous chondrocyte implantation. Each of these techniques has its own limitations, which led researchers to explore new regenerative and repair techniques to produce normal hyaline cartilage. The purpose of this Technical Note is to describe in detail the particulated autologous chondral-platelet-rich plasma matrix implantation (PACI) technique that could be used as a single-stage cartilage restoration procedure for treatment of full-thickness cartilage and osteochondral defects.

Outcomes at 2-Years Follow-Up After Hip Arthroscopy Combining Bone Marrow Concentrate.

Introduction: The cartilage injuries are related to femoroacetabular impingement (FAI). The prognostic of the injury depends on the grade of itself. Using bone marrow concentrate (BMC), which contains stem cells, is related to the improvement in diverse tissues. The purpose of this study was to evaluate the improvement of the patients after a FAI arthroscopic intervention using BMC. We compared the results to those of a previous cohort of patients who had identical surgery but without BMC. Methods: A cohort study was conducted between 2015 and 2017. Forty patients with FAI that underwent hip arthroscopy surgery combined with BMC were included. A control group of 40 patients with identical characteristics operated without BMC therapy. VAS, mHHS, and iHOT-33 preoperatively and at 3, 6, 12, and 24 months data were obtained and analyzed. Results: Significant differences between two groups where found at 12 and 24 months of follow-up. VAS values were significantly lower (p = 0.007 and p = 0.000). Pain and functional scales mHHS (p = 0.004 and p = 0.001) and iHOT (p = 0.033 and p = 0.024) were significantly higher in the study group.Conclusions: The use of BMC as coadyuvant in arthroscopic intervention of FAI injuries results in pain reduction and improvement in functionality as showed in VAS, mHHS, and iHOT-33 scores at 12 and 24 months of follow-up. Level of Evidence: Level of Evidence III, Case control study.

A novel autologous-made matrix using hyaline cartilage chips and platelet-rich growth factors for the treatment of full-thickness cartilage or osteochondral defects: Preliminary results.

PURPOSE: To report the clinical, functional, and magnetic resonance imaging (MRI)-based outcomes of a novel autologous-made matrix consisting of hyaline cartilage chips combined with mixed plasma poor rich in platelets clot and plasma rich in growth factors (PRGF) for the treatment of knee full-thickness cartilage or osteochondral defects. METHODS: Between July 2015 and January 2018, all patients with full-thickness cartilage or osteochondral defects undergoing this novel cartilage restoration surgical technique were approached for eligibility. Indications for this procedure included traumatic or atraumatic full-thickness knee cartilage defects or osteochondritis dissecans. Patients were included if they had no concomitant use of stem cells, previous ipsilateral cartilage repair procedure, or follow-up was less than 10 months. The outcomes included data on current symptoms, physical exam, patient-reported, and functional outcomes (visual analogue scale (VAS) for pain, Lysholm score, Tegner activity scale, International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lequesne index, and short form-12 (SF-12)) and the magnetic resonance observation of cartilage repair tissue (MOCART) score. These outcomes were compared to preoperative values, except for the MOCART score. RESULTS: Fifteen patients were included in this preliminary study: mean (standard deviation (SD), range) follow-up 15.9 months (7.2, 10-32), age 26.8 years (12.1, 16-58), and body mass index 23.2 (2.1, 19.3-26.9). There were 14 men (93%) and 1 woman (7%). There was a statistically significant improvement between pre- and postoperative periods for VAS for pain (p = 0.003), Lysholm score (p = 0.002), IKDC subjective form (p = 0.003), WOMAC for pain (p = 0.005), WOMAC for stiffness (p = 0.01), WOMAC for function (p = 0.002), Lequesne Index (p = 0.002), and SF-12 physical component summary (p = 0.007). The postoperative mean (SD; range) MOCART score was 70 (12.4; 40-85). CONCLUSIONS: The use of this novel cartilage restoration surgical technique provides excellent clinical, functional, and MRI-based outcomes in young, active individuals with full-thickness cartilage or osteochondral defects. LEVEL OF EVIDENCE: Level IV-Therapeutic case series.

Effects of autologous adipose-derived regenerative stem cells administered at the time of anterior cruciate ligament reconstruction on knee function and graft healing.

PURPOSE: To compare the healing and clinical outcomes of anterior cruciate ligament (ACL) reconstruction between patients with or without intraoperative administration of adipose-derived regenerative stem cells (ADRC). METHODS: Between 2013 and 2014, the outcomes of 20 soccer players undergoing ACL reconstruction using bone-patellar tendon-bone autograft infiltrated with ADRC at the end of the procedure were compared to a historical, matched cohort of 19 soccer players undergoing the same procedure without ADRC. Outcomes were obtained at baseline, and 6 and 12 months postop for IKDC (International Knee Documentation Committee), Lysholm, and Lequesne, and at 2, 4, 6, and 12 months postop for VAS (visual analogue scale) for pain and graft maturation to evaluate the ligamentization process (magnetic resonance imaging (MRI)-based). RESULTS: Both groups significantly improved the IKDC (p < 0.001 in both groups), Lysholm (p < 0.001 in both groups), Lequesne index (p < 0.001 in both groups), VAS for pain (p = 0.002 for the ADRC and p < 0.001 for the control group), and MRI scores (p < 0.001 in both groups) in the 12 months postop compared to baseline scores. However, there were no significant differences in the improvement of the outcomes between groups across time (p > 0.05). All patients returned to sports after surgery, but 8 (40%) patients in the ADRC and 13 (68.4%) patients in the control group had lower Tegner activity score at 12 months postop. CONCLUSIONS: Patients receiving ADRC at the time of ACL reconstruction significantly improved knee function and healing/maturation of the graft at 12 months. However, this improvement was not statistically significant compared to a control group undergoing ACL reconstruction alone.

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis.

The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

Effects of plasma rich in growth factors (PRGF) on biomechanical properties of Achilles tendon repair.

PURPOSE: To assess the biomechanical effects of intra-tendinous injections of PRGF on the healing Achilles tendon after repair in a sheep model. METHODS: Thirty sheep were randomly assigned into one of the six groups depending on the type of treatment received (PRGF or placebo) and survival time (2, 4 and 8 weeks). The Achilles tendon injury was repaired by suturing the tendinous edges employing a three-loop pulley pattern. A trans-articular external fixation system was then used for immobilization. The PRGF or placebo was administered on a weekly basis completing a maximum of three infiltrations. The force, section and tension values were compared between the operated and healthy Achilles tendons across all groups. RESULTS: The PRGF-treated tendons had higher force at 8 weeks compared with the placebo group (p = 0.007). Between 2 and 4 weeks, a significant increase in force in both the PRGF-treated tendon (p = 0.0027) and placebo group (p = 0.0095) occurred. No significant differences were found for section ratio between PRGF-treated tendons and the placebo group for any of the time periods evaluated. At 2 weeks, PRGF-treated tendons had higher tension ratio compared with placebo group tendons (p = 0.0143). Both PRGF and placebo treatments significantly improved the force (p < 0.001 and p = 0.0095, respectively) and tension (p = 0.009 and p = 0.0039, respectively) ratios at 8 weeks compared with 2 weeks. CONCLUSION: The application of PRGF increases Achilles tendon repair strength at 8 weeks compared with the use of placebo. The use of PRGF does not modify section and tension ratios compared with placebo at 8 weeks. The tension ratio progressively increases between 2 and 8 weeks compared with the placebo.

Biologic enhancement of cartilage repair: the role of platelet-rich plasma and other commercially available growth factors.

In part, people's quality of life depends on the "health" of their cartilage because its damage or deterioration causes pain that limits mobility and reduces autonomy. Predisposing genetic factors and modern-life environmental factors, such as diet, excessive physical exercise, or the absence of any physical exercise, in addition to injuries that can occur, all contribute to the onset and development of chronic degenerative diseases such as osteoarthritis. Regenerative medicine focuses on the repair, replacement, or regeneration of cells, tissues, or organs to restore impaired function from any cause, including congenital defects, disease, and trauma.

Healing of donor site in bone-tendon-bone ACL reconstruction accelerated with plasma rich in growth factors: a randomized clinical trial.

PURPOSE: To determine whether the use of plasma rich in growth factors accelerates healing of the donor site in bone-tendon-bone anterior cruciate ligament (ACL) reconstruction (patellar graft). The use of the patellar graft presents post-operative problems such as anterior knee pain, which limits its use and leads to preference being taken for alternative grafts. METHODS: A double-blind, randomized, clinical trial was performed comparing two groups of patients who underwent ACL reconstruction using patellar tendon graft and comparing the use of plasma rich in growth factors at the donor site after graft harvest in terms of local regeneration by ultrasound assessment. RESULTS: The plasma rich in growth factors group shows earlier donor site regeneration in comparison with the control group (2 months earlier), with significant differences in the first 4 months of the follow-up. CONCLUSION: The application of plasma rich in growth factors shows accelerated tissue regeneration processes with respect to the control group. This fact, together with the previously published with similar conclusions, can create a knowledge basis in order to set out new recovery guidelines following ACL reconstruction. LEVEL OF EVIDENCE: Therapeutic study, Level I.

Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep.

BACKGROUND: The use of plasma rich in growth factors (PRGF) has been proposed to improve the healing of Achilles tendon injuries, but there is debate about the effectiveness of this therapy. The objective of the present study was to evaluate the histological effects of PRGF, which is a type of leukocyte-poor platelet-rich plasma, on tendon healing. METHODS: The Achilles tendons of twenty-eight sheep were divided surgically. The animals were randomly divided into four groups of seven animals each. The repaired tendons in two groups received an infiltration of PRGF intraoperatively and every week for the following three weeks under ultrasound guidance. The tendons in the other two groups received injections with saline solution. The animals in one PRGF group and one saline solution group were killed at four weeks, and the animals in the remaining two groups were killed at eight weeks. The Achilles tendons were examined histologically, and the morphometry of fibroblast nuclei was calculated. RESULTS: The fibroblast nuclei of the PRGF-treated tendons were more elongated and more parallel to the tendon axis than the fibroblast nuclei of the tendons in the saline solution group at eight weeks. PRGF-treated tendons showed more packed and better oriented collagen bundles at both four and eight weeks. In addition to increased maturation of the collagen structure, fibroblast density was significantly lower in PRGF-infiltrated tendons. PRGF-treated tendons exhibited faster vascular regression than tendons in the control groups, as demonstrated by a lower vascular density at eight weeks. CONCLUSIONS: PRGF was associated with histological changes consistent with an accelerated early healing process in repaired Achilles tendons in sheep after experimental surgical disruption. PRGF-treated tendons showed improvements in the morphometric features of fibroblast nuclei, suggesting a more advanced stage of healing. At eight weeks, histological examination revealed more mature organization of collagen bundles, lower vascular densities, and decreased fibroblast densities in PRGF-treated tendons than in tendons infiltrated with saline solution. These findings were consistent with a more advanced stage of the healing process. CLINICAL IMPLICATIONS: Based on the findings in this animal model, PRGF infiltration may improve the early healing process of surgically repaired Achilles tendons.

Platelet-rich plasma for calcific tendinitis of the shoulder: a case report.

We report a 44-year-old woman with calcific tendinitis of the shoulder treated with platelet-rich plasma injection. Prior to this, she had no improvement of the symptoms after 6 weeks of ultrasound treatment, Codman exercises, and anti-inflammatory treatment. Platelet-rich plasma was injected into the subacromial area 3 times at 2-week intervals. She had progressive improvement of pain after 2 weeks, and was asymptomatic at week 6. The patient then underwent the previous protocol of rehabilitation. At the one-year follow-up, the patient was pain-free and had complete resolution of calcific tendinitis. The patient had regained full range of movement and had resumed all her activities.

Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life.

PURPOSE: Osteoarthritis (OA) is a highly prevalent, chronic, degenerative condition that generates a high expense. Alternative and co-adjuvant therapies to improve the quality of life and physical function of affected patients are currently being sought. METHODS: A total of 808 patients with knee pathology were treated with PRGF (plasma rich in growth factors), 312 of them with OA of the knee (Outerbridge grades I-IV) and symptoms of >3 months duration met the inclusion criteria and were evaluated to obtain a sample of 261 patients, 109 women and 152 men, with an average age of 48.39. Three intra-articular injections of autologous PRGF were administered at 2-week intervals in outpatient surgery. The process of obtaining PRGF was carried out following the Anitua Technique. Participants were asked to fill out a questionnaire with personal data and the following assessment instruments: VAS, SF-36, WOMAC Index and Lequesne Index before the first infiltration of PRGF and 6 months after the last infiltration. RESULTS: Statistically significant differences (P < 0.0001) between pre-treatment and follow-up values were found for pain, stiffness and functional capacity in the WOMAC Index; pain and total score, distance and daily life activities in the Lequesne Index; the VAS pain score; and the SF-36 physical health domain. There were no adverse effects related to PRGF infiltration. CONCLUSION: At 6 months following intra-articular infiltration of PRGF in patients with OA of the knee, improvements in function and quality of life were documented by OA-specific and general clinical assessment instruments. These favourable findings point to consider PRGF as a therapy for OA.

Arthroscopic meniscal allograft transplantation without bone plugs.

Partial or total meniscectomy are common procedures performed at Orthopedic Surgery departments. Despite providing a great relief of pain, it has been related to early onset knee osteoarthritis. Meniscal allograft transplantation has been proposed as an alternative to meniscectomy. The purposes of this study were to describe an arthroscopic meniscal allograft transplantation without bone plugs technique and to report the preliminary results. All meniscal allograft transplantations performed between 2001 and 2006 were approached for eligibility, and a total of 35 patients (involving 37 menisci) were finally engaged in the study. Patients were excluded if they had ipsilateral knee ligament reconstruction or cartilage repair surgery before meniscal transplantation or other knee surgeries after the meniscal transplantation. Scores on Lysholm, Subjective IKDC Form, and Visual Analogue Scale (VAS) scale for pain were obtained at a mean follow-up of 38.6 months and compared to pre-operative data. Data on chondral lesions were obtained during the arthroscopic procedure and through imaging (radiographs and MRI) studies pre-operatively. Two graft failures out of 59 transplants (3.4%) were found. Daily life accidents were responsible for all graft failures. Significant improvements for Lysholm, Subjective IKDC Form, and VAS for pain scores following the meniscal allograft transplantation were found (P < 0.0001). Controlling for chondral lesion, there was no significant interactions for Lysholm (n.s.), Subjective IKDC Form (n.s.), and VAS for pain scores (n.s.). This study demonstrated that an arthroscopic meniscal allograft transplantation without bone plugs improved knee function and symptoms after a total meniscectomy. Improvements were observed independently of the degree of chondral lesion.

Delayed union of the clavicle treated with plasma rich in growth factors.

Nonunion is an uncommon complication of fracture of the clavicle; it is usually treated surgically. The use of biological treatments in this type of condition is increasingly more common because of their ease of application. Plasma rich in growth factors (PRGF) has been used in delayed healing and in nonunion of fractures. We report a case of delayed union fracture of the clavicle in which biological treatment was chosen before considering surgery. Three percutaneous injections of PRGF, one every 2 weeks, were delivered into the delayed union site. The autologous PGRF used was obtained through the patented PRGF system. Three months after the final dose, computed tomography study showed healing of the bone. The patient regained complete mobility of the shoulder without pain. Currently she is able to carry out all the normal life activities and experiences no pain.

Superior dislocation of the patella: a case report.

BACKGROUND: Superior dislocation of the patella is an uncommon condition that mainly occurs in knees with a high patella and medial femorotibial degenerative arthritis. There are no previous reports of this condition occurring in association with tibial valgus osteotomy. CASE REPORT: We report the case of a patient in whom vertical dislocation recurred twice at 4 months after tibial valgus osteotomy. To avert additional recurrence or new dislocations, the patient was treated surgically to remove the existing osteophytes. CONCLUSIONS: An arthroscopic approach was decided because of the lower associated morbidity and good results with this technique compared to open surgery.