Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects, and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

/pdf/platelet-rich-plasma-new-performance-understandings-and-1ip2hrbii1.pdf

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

Low back pain (LBP), as a leading cause of disability, is a common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration, a significant contributor to LBP. Inflammatory mediators also play an indispensable role in discogenic LBP. The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies. Here, an overview of the advances in inflammation-related pain in disc degeneration is provided, with a discussion on the role of inflammation in IVD degeneration and pain induction. Puncture models, mechanical models, and spontaneous models as the main animal models to study painful disc degeneration are discussed, and the underlying signaling pathways are summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing clinical trials, to suppress discogenic LBP by eliminating inflammation are explored. We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.

/pdf/painful-intervertebral-disc-degeneration-and-inflammation-2hn485rh6r.pdf

Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions.

Although platelets are widely recognized as having a critical role in primary hemostasis and thrombosis, increasing experimental and clinical evidence identifies these enucleated cells as relevant modulators of other physiopathological processes including inflammation and tissue regeneration. These phenomena are mediated through the release of growth factors, cytokines, and extracellular matrix modulators that sequentially promote (i) revascularization of damaged tissue through the induction of migration, proliferation, differentiation, and stabilization of endothelial cells in new blood vessels; (ii) restoration of damaged connective tissue through migration, proliferation, and activation of fibroblasts; and (iii) proliferation and differentiation of mesenchymal stem cells into tissue-specific cell types. For these reasons, platelet-rich plasma (PRP) derivatives are used in regenerative medicine for the treatment of several clinical conditions including ulcers, burns, muscle repair, bone diseases, and tissue recovery following surgery. The benefits of PRP administration are associated with an economical advantage, taking into consideration that PRP administration does not require complex equipment or training for its execution. Moreover, due to their primary autologous origin, concerns of disease transmission or immunogenic reactions can be disregarded. Thus, platelet-enriched materials have become highly relevant in the last decade and constitute a growing focus of experimental and clinical study in the context of wound healing and tissue regeneration. However, despite the diverse applications, the efficacy of regenerative treatments using PRP is being called into question due to the lack of large controlled clinical trials and the lack of consensus regarding the PRP preparation techniques. This review describes the biological mechanisms underlying PRP's regenerative effects, the different methods of preparation and application of these biomaterials, and the controversies and future prospects related to the use of PRP in regenerative medicine.

Platelets in wound healing and regenerative medicine.

Substantial advancements have been made in the cause, diagnosis, imaging, and treatment options available for patients with lumbar disc herniation (LDH). We examined the current evidence and highlight the concepts on the frontline of discovery in LDH. There are a myriad of novel etiologies of LDH detailed in recent literature including inflammatory factors and infectious microbes. In the clinical setting, recent data focuses on improvements in computer tomography as a diagnostic tool and non-traditional injection options including tumor necrosis alpha inhibitors and platelet-rich plasma. Operative treatment outcomes have focused on minimally invasive endoscopic approaches and demonstrated robust 5-year post-operative outcomes. Advances in the molecular etiology of LDH will continue to drive novel treatment options. The role of endoscopic treatment for LDH will continue to evolve. Further research into10-year outcomes will be necessary as this surgical approach continues to gain widespread popularity.

Lumbar Disc Herniation.

Objective To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Design Prospective, double-blind, randomized controlled study. Setting Outpatient physiatric spine practice. Participants Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Methods Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Main Outcome Measures Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Results Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) ( P = .02), function (FRI) ( P = .03), and patient satisfaction (NASS Outcome Questionnaire) ( P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Conclusion Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP injectate.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study

Objective: To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Design: Prospective, double-blind, randomized controlled study. Setting: Outpatient physiatric spine practice. Participants: Adults with chronic (� 6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Methods: Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Main Outcome Measures: Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Results: Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P ¼ .02), function (FRI) (P ¼ .03), and patient satisfaction (NASS Outcome Questionnaire) (P ¼ .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Conclusion: Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP injectate.

Original ResearchdCME Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study

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Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study

Original ResearchdCME Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study