Plasma Rich in Growth Factors (PRGF) in the Treatment of Patients With Chronic Cervical and Lumbar Pain: A Prospective Observational Clinical Study.

BACKGROUND: Chronic back pain is a long-lasting disorder, whose main source of pain is often the intervertebral disc that undergoes a degenerative process associated with low-grade inflammation, leading to a reduced quality of life. OBJECTIVES: The aim of our study was to assess the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) in patients with chronic clinical symptoms due to intervertebral disc (IVD) degeneration. STUDY DESIGN: Prospective observational study. SETTING: A single spine unit in a private clinic. METHODS: Thirty-two patients with cervical and lumbar chronic pain due to IVD degeneration were treated with 2 or 3 series of intradiscal and epidural PRGF infiltrations with 2 weeks between each procedure. The procedures were performed under fluoroscopic guidance and grade 3 sedation in an operating theater. Treatment efficacy was evaluated using the Spine Tango Core Outcome Measure Index questionnaire, Numeric Rating Scale for back pain, and the Oswestry Disability Index questionnaire. In addition, the number of patients who successfully achieved the minimal clinically important change was also determined. These assessments were evaluated at pretreatment (baseline) and at one, 3, and 6 months posttreatment. RESULTS: The Oswestry Disability Index, COMI Spine Tango Core Outcome Measure Index total score, and Numeric Rating Scale showed a statistically significant reduction from the baseline level to the posttreatment first month, third month, and sixth month (P < 0.001). Moreover, 78.1% of the patients reached a pain reduction superior to 30% one month posttreatment, and 87.5% at 6 months posttreatment, which is considered as a clinically significant improvement. LIMITATIONS: This study was prospective and did not have a control group. Only patient-reported outcomes were evaluated. CONCLUSIONS: This observational, prospective study of patients with chronic back pain showed that 2-3 intradiscal and epidural injections of PRGF significantly decreased pain and disability at one month posttreatment and this improvement was maintained, and in some patients even improved, at 3, and 6 months posttreatment.

Surgical Treatment of Saphenous Nerve Injury Assisted by Plasma Rich in Growth Factors (PRGF): Lessons from a Case Report.

The infrapatellar branch of the saphenous nerve (SN) is a widely described anatomic and functional structure; however, its relevance in daily clinical practice is underestimated. All surgical procedures performed on the anteromedial aspect of the knee are associated with a risk of iatrogenic injury to this nerve, including knee arthroscopy, knee arthroplasty, tibial nailing, etc. We present the case of a saphenous nerve neuroma after treatment with radiofrequency thermal ablation due to a knee pain problem. After conducting an anaesthetic suppression test, we decided to perform a denervation of the medial saphenous nerve in Hunter's canal. We performed surgery on the anteromedial aspect of the knee. The distal end of the medial SN was coagulated with a bipolar scalpel. The proximal end of the nerve was released proximally, and a termino-lateral suture was made at the free end of the nerve after creating an epineural window to inhibit its growth. A double crush was produced proximally to the suture site to create a grade II-III axonal injury. Autologous plasma rich in growth factors (PRGF) was used to reduce potential post-surgical adhesions and to stimulate regeneration of the surgical lesions. One year after surgery, the patient was living a completely normal life.

An evolutionary history of F12 gene: Emergence, loss, and vulnerability with the environment as a driver.

In the context of macroevolutionary transitions, environmental changes prompted vertebrates already bearing genetic variations to undergo gradual adaptations resulting in profound anatomical, physiological, and behavioral adaptations. The emergence of new genes led to the genetic variation essential in metazoan evolution, just as was gene loss, both sources of genetic variation resulting in adaptive phenotypic diversity. In this context, F12-coding protein with defense and hemostatic roles emerged some 425 Mya, and it might have contributed in aquatic vertebrates to the transition from water-to-land. Conversely, the F12 loss in marine, air-breathing mammals like cetaceans has been associated with phenotypic adaptations in some terrestrial mammals in their transition to aquatic lifestyle. More recently, the advent of technological innovations in western lifestyle with blood-contacting devices and harmful environmental nanoparticles, has unfolded new roles of FXII. Environment operates as either a positive or a relaxed selective pressure on genes, and consequently genes are selected or lost. FXII, an old dog facing environmental novelties can learn new tricks and teach us new therapeutic avenues.

Office-Based Intraosseous Infiltrations of PRGF as an Effective Treatment for Knee Osteoarthritis: A Retrospective Observational Clinical Study.

The aim of this study was to explore and assess office-based ultrasound-guided intraosseous and intra-articular infiltrations of plasma rich in growth factors (PRGF) in patients with moderate and severe knee osteoarthritis (KOA). Seventy-nine patients (30 women and 49 men) with grade 3-4 KOA according to the Kellgren-Lawrence classification participated in the study. All patients were treated with a minimally invasive technique using local anesthesia WALANT (wide-awake local anesthesia no tourniquet) in the ambulatory setting. A PRGF intra-articular infiltration and two intraosseous infiltrations in the tibial plateau and femoral condyle were performed weekly for a total of three sessions. The evaluation of the results was carried out using knee injury and osteoarthritis outcome score (KOOS) at baseline and post-treatment. After a follow-up period of 11 months (median) [interquartile range, 7-14], all the KOOS domains showed statistically significant improvement (p < 0.001). Moreover, 88% of the patients showed a pain reduction of at least 10 points (minimally clinically important improvement) from pre- to post-treatment. Our retrospective study using the in-office procedure of ultrasound-guided combination of intra-articular and intraosseous infiltrations of PRGF is a safe and efficacious approach for the treatment of grade 3-4 knee osteoarthritis.

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.

Plasma rich in growth factors versus corticosteroid injections for management of chronic rotator cuff tendinopathy: a prospective double-blind randomized controlled trial with 1 year of follow-up.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a painful and dysfunctional shoulder condition traditionally considered as a degenerative pathology. However, evidence is pointing to immunocompetent cells and activated stromal fibroblasts as the drivers of a nonresolved inflammatory condition in RCT. As potent anti-inflammatory agents, corticosteroid injections have been among the first-line and the most common therapeutic strategies. Recently, another adjuvant therapy to treat musculoskeletal inflammation-driven painful conditions, namely, platelet-rich plasma (PRP), has emerged as safe and effective. The aim of this study was to compare the clinical efficacy of intratendinous injections of plasma rich in growth factors (PRGF) with conventional intratendinous corticosteroid injections on patients with chronic RCT using patient-reported outcome measures. METHODS: A total of 39 patients received PRGF treatment (3 infiltrations, 1 every other week), whereas 40 patients, as a control group, received corticosteroid (3 infiltrations, 1 every other week). Patients were evaluated before treatment and at 3, 6, and 12 months of follow-up using the University of California Los Angeles (UCLA) scale, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Constant test. The primary outcome of the study was a 15% superior improvement of the PRGF group compared with the corticosteroid group in the UCLA scale and QuickDASH test at 6 months of follow-up, considering this difference to be clinically relevant. RESULTS: Both PRGF and corticosteroid groups showed significant clinical improvement in the 3 scores at all time points of the study compared with baseline. However, at 6 and 12 months of follow-up, the PRGF group had 22.1% and 21.2% superior improvement of the UCLA test, 14.3% and 13.5% for QuickDASH, and 16.4% and 20.2% for the Constant-Murley test, respectively, compared to the corticosteroid group. CONCLUSIONS: Three PRGF intratendinous injections every other week in patients with chronic rotator cuff tendinopathy show significantly superior and sustained pain-relieving and functional improvements compared with corticosteroid intratendinous injections assessed by 3 patient-reported outcome scales at 6 and 12 months of follow-up.

Reconstruction of Chronic Proximal Hamstring Tear: A Novel Surgical Technique with Semitendinosus Tendon Allograft Assisted with Autologous Plasma Rich in Growth Factors (PRGF).

The reconstruction of a chronic proximal hamstring tear is a challenging pathology that posits difficulties to surgeons due to the distal retraction of the hamstring tendon stumps and the entrapment of the sciatic nerve within the scar formed around the torn hamstring tendon. We describe a novel surgical technique using a semitendinosus tendon allograft sutured in a "V inversion" manner, thereby avoiding an excess of tension and length of the new reconstructed hamstring tendons. In addition, and in order to speed up the healing process and avoid new sciatic entrapment, we assisted the surgery with liquid plasma rich in growth factors (PRGF) injected intraosseously, intratendinously and within the suture areas, as well as wrapping the sciatic nerve with a PRGF membrane. In conclusion, this novel approach offers mechanical and biological advantages to tackle the large retraction of hamstring stumps and the entrapment of the sciatic nerve within the scar.

The Effectiveness of Plasma Rich in Growth Factors (PRGF) in the Treatment of Nerve Compression Syndromes of the Upper Extremity: A Retrospective Observational Clinical Study.

Background: Nerve compression syndromes of the upper extremity are a common cause of neuropathic pain and functional impairment. Recently, platelet-rich plasma (PRP) infiltrations have emerged as an effective biological approach to the treatment of this type of injury. The objectives of this retrospective observational study were to assess clinical improvement in patients with median and ulnar nerve entrapment syndrome after undergoing biologically-assisted nerve release surgery with plasma-rich-in-growth-factors (PRGF) technology. Methods: Participants (n = 39) with moderate-to-severe nerve compression syndrome of the upper limb diagnosed by both electromyography and clinical examination, and who were treated with PRGF, were identified from the center's medical records. The evaluation was based on patient-reported outcomes. Pre- and post-treatment differences in the Visual analog scale (VAS), the Boston carpal tunnel questionnaire (BCTQ), and the Quick-DASH score were assessed. Results: Three study groups were conducted: patients with carpal tunnel syndrome (n = 16), with recurrent carpal tunnel syndrome (n = 8), and with ulnar nerve entrapment (n = 15). The median follow-up was 12 months (interquartile range (IQR), 9−16). In comparison to pre-treatment values, all three study groups obtained statistically significant improvements for the three analyzed scales at the end of the follow-up, with p < 0.001 for all scales in the carpal tunnel syndrome and ulnar nerve entrapment groups and p < 0.01 for all scales in the recurrent carpal tunnel syndrome group. There were no serious adverse effects in the analyzed patients. Conclusion: PRGF-assisted open surgical nerve release treatment (intraneural and perineural liquid PRGF infiltrations and nerve wrapping with PRGF membrane) exerts long-term beneficial effects on pain reduction and functional improvement in the nerve and nerve−muscle unit in patients with upper extremity compression syndromes.

Evolutionary Insight into Immunothrombosis as a Healing Mechanism.

Both invertebrates and vertebrates possess a cluster of immediate and local wound-sealing, pathogen-killing, and tissue healing responses known as immunoclotting and immunothrombosis, respectively, to cope with two life-threatening emergencies, namely, bleeding and microbial invasion. Despite their convergence in function, immunoclotting and immunothrombosis are deployed by different blood cells and intravascular multidomain proteins. In vertebrates, these proteins share some domains with intrinsic chemical affinities useful in generating cooperative networks such as pathogen and damage pattern recognition molecules. Moreover, many of the proteins involved in coagulation and fibrinolysis in humans are multifunctional molecules playing roles in other processes from inflammation to healing and beyond. In our modern society, however, the interaction of activated intravascular allosteric proteins with one another and with blood cells entails vulnerabilities posing a biological paradox: intravascular proteins that locally operate as tissue repair enhancers can nevertheless generate pathogenic processes by acting systemically. In this manuscript, we contextualize and frame the coagulation system and hemostasis through an evolutionary time scale, illustrating their role as dual players in the defense against exsanguination and pathogens while significantly influencing wound healing.

Office-Based Intraosseous Infiltrations of PRGF in Knee Osteoarthritis: Description of Technique.

Knee osteoarthritis is a low-degree inflammatory condition that involves the whole synovial joint tissues as an organ. Recently, a biological approach using plasma rich in growth factors (PRGF) to tackle not only the synovial joint with intraarticular injections of PRGF, but also the subchondral bone with intraosseous infiltrations has been implemented with promising results. However, this procedure requires sedation, which limits the implementation of the procedure to operating room. We propose a modified and less cumbersome PRGF intraosseous infiltration approach for moderate and severe knee osteoarthritis, conducting the procedure in the ambulatory setting assisted with WALANT (wide-awake local anesthesia no tourniquet) technique. The proposed technique with a minimally invasive local anesthesia involves subcutaneous infiltration of lidocaine and epinephrine in a solution without sedation, and using ultrasound guidance, thereby streamlining the original procedure. This procedure is both a cost-effective and safe approach that may contribute to the widespread use of intraosseous infiltrations.

Healing through the lens of immunothrombosis: Biology-inspired, evolution-tailored, and human-engineered biomimetic therapies.

Evolution, from invertebrates to mammals, has yielded and shaped immunoclotting as a defense and repair response against trauma and infection. This mosaic of immediate and local wound-sealing and pathogen-killing mechanisms results in survival, restoration of homeostasis, and tissue repair. In mammals, immunoclotting has been complemented with the neuroendocrine system, platelets, and contact system among other embellishments, adding layers of complexity through interconnecting blood-born proteolytic cascades, blood cells, and the neuroendocrine system. In doing so, immunothrombosis endows humans with survival advantages, but entails vulnerabilities in the current unprecedented and increasingly challenging environment. Immunothrombosis and tissue repair appear to go hand in hand with common mechanisms mediating both processes, a fact that is underlined by recent advances that are deciphering the mechanisms of the repair process and of the biochemical pathways that underpins coagulation, hemostasis and thrombosis. This review is intended to frame both the universal aspects of tissue repair and the therapeutic use of autologous fibrin matrix as a biology-as-a-drug approach in the context of the evolutionary changes in coagulation and hemostasis. In addition, we will try to shed some light on the molecular mechanisms underlying the use of the autologous fibrin matrix as a biology-inspired, evolution-tailored, and human-engineered biomimetic therapy.

Plasma Rich in Growth Factors (PRGF) in the Treatment of Cervical and Lumbar Back Pain: A Retrospective Observational Clinical Study.

BACKGROUND: Plasma rich in growth factors (PRGF) is a leukocyte-free platelet-rich plasma (PRP) that is an effective biological approach to tissue repair and has been demonstrated to significantly improve multiple conditions, including low back pain and degenerative disc pathology. OBJECTIVES: The objective of this retrospective study was to analyze the effectiveness of treating both cervical and lumbar spine pain with minimally invasive infiltrations of PRGF-Endoret. STUDY DESIGN: Retrospective study design. SETTING: Outpatient private practice facility. METHODS: The effectiveness of PRGF has been assessed by patient-reported outcomes (PRO) through validated questionnaires, namely Numeric Rating Scale (NRS) for back pain, Spine Tango Core Outcome Measure Index (COMI) Questionnaire for lumbar and cervical pain, and OSWESTRY Disability Index questionnaire for lumbar pain cases. Score differences between pre- and post-treatment have also been assessed stratified for multiple sub-groups of patients based on the sector of the column treated, gender, and age. RESULTS: This study includes 65 patients (18 with cervical pain and 47 with lumbar back pain). The average time of back pain evolution was 10 years. Patients received at least 2 PRGF infiltration series about one month apart. Each patient received intervertebral disc and epidural infiltrations, root infiltrations, in case of radicular injury, and intraarticular infiltrations, in case of osteoarthritis of the facet joints. Results show statistically significant (P < 0.05) improvements on all analyzed scores. Regarding the stratified analyses, 249 (99%) sub-groups showed an improvement in all tests (252 cases overall). From the 249 improving cases, 154 (62%) showed a statistically significant difference between the pre- and the post- treatment periods. LIMITATIONS: This research is a retrospective study with a relatively small sample cohort. Only PRO have been assessed. CONCLUSIONS: According to the results obtained in this study, and taking into account their limitations, PRGF infiltrations are an effective and minimally invasive biological strategy in the treatment of both cervical and lumbar pain, evaluated according to PRO.

Platelet-Rich Plasma Applications for Achilles Tendon Repair: A Bridge between Biology and Surgery.

Achilles tendon ruptures are very common tendon ruptures and their incidence is increasing in modern society, resulting in work incapacity and months off sport, which generate a need for accelerated and successful therapeutic repair strategy. Platelet-rich plasma (PRP) is emerging as adjuvant human blood-derived constructs to assist Achilles tendon rupture treatment. However, myriad PRP preparation methods in conjunction with poor standardization in the modalities of their applications impinge on the consistent effectiveness of clinical and structural outcomes regarding their therapeutic efficacy. The purpose of this review is to provide some light on the application of PRP for Achilles tendon ruptures. PRP has many characteristics that make it an attractive treatment. Elements such as the inclusion of leukocytes and erythrocytes within PRP, the absence of activation and activation ex vivo or in vivo, the modality of application, and the adjustment of PRP pH can influence the biology of the applied product and result in misleading therapeutic conclusions. The weakest points in demonstrating their consistent effectiveness are primarily the result of myriad PRP preparation methods and the poor standardization of modalities for their application. Selecting the right biological scaffold and applying it correctly to restitutio ad integrum of ruptured Achilles tendons remains a daunting and complex task.

Vertebral intraosseous plasma rich in growth factor (PRGF-Endoret) infiltrations as a novel strategy for the treatment of degenerative lesions of endplate in lumbar pathology: description of technique and case presentation.

BACKGROUND: Motivation and necessity to adopt minimally invasive therapies in the field of spinal regenerative medicine is increasing. Autologous platelet-rich plasma (PRP) therapy has recently been used as an effective technological and biological approach to tissue repair and has shown to improve multiple conditions including back pain and degenerative disc pathology. In addition, it is well established that the anatomic elements of the spinal system affected by degenerative pathology include the intervertebral disc (IVD) and vertebral subchondral bone (VSB), which play a crucial role in maintaining a healthy spinal column. Both elements are the target of a novel biological approach to the treatment of low back pain. METHODS: A novel minimally invasive regenerative therapeutic approach is presented herein with a protocol based on combining vertebral intraosseous (VIO) and intradiscal (ID) infiltrations of plasma rich in growth factors (PRGF-Endoret), a type of leukocyte-free PRP, for the treatment of disc degeneration pathology. RESULTS: We describe a novel technique applied in a patient treated for IVD degeneration and VSB damage, showing significant improvement on magnetic resonance imaging, including partial regression of protruded disc and significant resorption of intravertebral herniations (Schmörl's nodes), after PRGF therapy. CONCLUSIONS: To the best of our knowledge, we present the first reported case description of the utilization of VIO and ID PRP infiltrations to treat protruded discs and intravertebral herniations with a successful clinical outcome.

Platelet-rich plasma combined with allograft to treat osteochondritis dissecans of the knee: a case report.

BACKGROUND: Osteochondritis dissecans of the knee is a prevalent pathology in young, active people that is brought about by either traumatic, developmental, or iatrogenic etiologies. CASE PRESENTATION: A 40-year-old Caucasian man reporting pain, swelling, and functional reduction was evaluated and diagnosed with internal condyle osteochondritis dissecans of the knee. Harnessing the trophic, chondroprotective, anti-inflammatory, and immunomodulatory properties of platelet-rich plasma, we carried out a knee open-sky surgical technique in which we combined autologous therapy with osteochondral allograft to treat the focal, large, and deep traumatic-iatrogenic osteochondritis dissecans of the knee. The axial computed tomographic scan taken 1 year after surgery revealed an area of abnormal signal intensity that was reduced on a computed tomographic scan 2 years later. The computed tomographic scan obtained 2 years later and the magnetic resonance imaging scan 3 years later also showed a clear reattachment and incorporation of the graft. Seven years after the surgery, the patient resumed his daily routine without any recurrent symptoms. CONCLUSION: Platelet-rich plasma application in osteochondral allograft implantation open surgery could enhance the healing process of medial condyle osteochondritis dissecans of the knee.

Treating Severe Knee Osteoarthritis with Combination of Intra-Osseous and Intra-Articular Infiltrations of Platelet-Rich Plasma: An Observational Study.

OBJECTIVE: Assessing the therapeutic effects of a combination of intra-articular and intra-osseous infiltrations of platelet-rich plasma (PRP) to treat severe knee osteoarthritis (KOA) using intra-articular injections of PRP as the control group. DESIGN: In this observational study, 60 patients suffering from severe KOA were treated with intra-articular infiltrations of PRP (IA group) or with a combination of intra-osseous and intra-articular infiltrations of PRP (IO group). Both groups were matched for sex, age, body mass index, and radiographic severity (III and IV degree according to Ahlbäck scale). Clinical outcome was evaluated at 2, 6, and 12 months, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires. RESULTS: At 2, 6 and 12 months after treatment, IO group had a significant improvement in all KOOS and WOMAC subscales ( P < 0.05). On the contrary, patients of the IA group did not improve in any of the scores. Sixteen out of 30 IO group patients showed minimal clinically important improvement (MCII) whereas 8 out of 30 IA group patients showed this response at 6 months (26.7%; 95% CI -0.4 to 49.9; P = 0.037). At 12 months, 14 patients of IO group and 5 patients of the IA group showed MCII (30%; 95% CI 4.3 to 51.9; P = 0.013). No differences between groups were observed at 2 months. CONCLUSIONS: PRP intra-articular injections in severe KOA were not effective and did not provide any benefit. Combination of intra-articular and intra-osseous infiltrations of PRP was not clinically superior at 2 months, but it showed superior clinical outcomes at 6 and 12 months when compared with intra-articular injections of PRP.