Advances in Autologous PRP Therapy

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 26560

Special Issue Editor


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Guest Editor
1. Cell Therapy Department, Marseille University Hospital, APHM, 13005 Marseille, France
2. Center of Cardiovascular Research & Nutrition, Pharmacy Faculty, Aix Marseille University, 13385 Marseille, France
3. Bioengineering Department, Pharmacy Faculty, Aix Marseille University, 13385 Marseille, France
Interests: regenerative medicine; platelet-rich plasma; stem cell therapy; adipose tissue

Special Issue Information

Dear Colleagues,

Platelet rich plasma (PRP) is an autologous biological product defined by a supraphysiological concentration of platelets and containing bioactive proteins, such as growth, factors, cytokines, and chemokines. Autologous PRP therapies have been used for more than 30 years, resulting in considerable interest in the field of regenerative medicine among diverse specialties. On one hand, PRP therapies are becoming suitable treatment options with clinical benefits and encouraging patient outcomes reported. On the other hand, production heterogeneity of PRP, the absence of systematic and standardized biological characterization, and an unclear mechanism of action have led to controversial results compared to other reference treatments and contributed to the fact that this therapy is struggling to be recognized as effective by the learned societies and still not covered by insurance companies.

This Special Issue of Bioengineering, titled “Advances in Autologous Platelet-Rich Plasma Therapy”, will focus on recent advances in autologous PRP therapy research for therapeutic purposes, with no limit regarding the specialties using PRP. Contributions of this Special Issue will include a broad spectrum of scientific articles involving original research, reviews, or meta-analyses. The research work submitted may be in vitro or in vivo experiments with a special interest for papers focusing on comprehension of PRP and platelets extracellular vesicles mechanism of action, as well as clinical studies, case series, or real-life studies in a context of therapeutic use.

Authors are invited to detail the qualitative and quantitative composition of the autologous biological products studied.

Dr. Jeremy Magalon
Guest Editor

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Keywords

  • platelets
  • growth factors
  • platelet-rich plasma
  • regenerative medicine
  • autologous biological product
  • extracellular vesicles
  • exosome
  • biological characterization
  • quality control
  • real world evidence

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Published Papers (9 papers)

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Research

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11 pages, 298 KiB  
Article
SAS-PRP Study: A Real-Life Satisfaction Assessment in Patients with Cartilage Lesions of the Knee Treated by Platelet-Rich Plasma
by Romain Verron, Lucie Zhang, Hélène Bisseriex, Ronan Grimandi, Alix Verrando, Claire Verdaguer, Marie Thomas, Julia Facione and Leo Borrini
Bioengineering 2023, 10(11), 1276; https://doi.org/10.3390/bioengineering10111276 - 2 Nov 2023
Cited by 1 | Viewed by 1749
Abstract
Platelet-rich plasma (PRP) is a rising therapy treating locomotor system lesions such as knee osteoarthritis. The objective of this study was to evaluate patients’ satisfaction 6 to 12 months after a PRP injection for cartilage lesions of their knee under real-life conditions. Patients’ [...] Read more.
Platelet-rich plasma (PRP) is a rising therapy treating locomotor system lesions such as knee osteoarthritis. The objective of this study was to evaluate patients’ satisfaction 6 to 12 months after a PRP injection for cartilage lesions of their knee under real-life conditions. Patients’ satisfaction was assessed by a specific questionnaire named SATMED-Q©, which explores six different dimensions of a given treatment. In addition, pain and function were assessed thanks to VAS pain, WOMAC, and IKDC scores. Responders were identified through the OMERACT-OARSI criteria. We observed excellent satisfaction after a PRP injection with a SATMED-Q© score of 80.81% 6 to 12 months after the procedure. Even when there was no significant improvement in pain and function scores, 52% of the evaluated population fulfilled the OMERACT-OARSI criteria and were considered responders. According to the sub-group analysis, patients with less osteoarthritis damage (i.e., Kellgren–Lawrence grades 1–2) and older study subjects (i.e., >40 years old) with focal chondropathy had benefited most from their PRP injection. Thus, platelet-rich plasma seems to be a well-tolerated and efficient therapy for cartilage lesions of the knee. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
14 pages, 2402 KiB  
Article
Optimizing Platelet-Rich Plasma: Spin Time and Sample Source
by Theodore E. Harrison, Jannice Bowler, Chin-I Cheng and Kenneth Dean Reeves
Bioengineering 2023, 10(11), 1270; https://doi.org/10.3390/bioengineering10111270 - 31 Oct 2023
Cited by 2 | Viewed by 2382
Abstract
The buff-colored layer separating the plasma from red blood cells (RBCs) in centrifuged blood was named the “buffy coat” in the late 19th century. The division of platelets (PLTs) and leukocytes (WBCs) between the buffy coat, plasma, and RBC layers in centrifuged blood [...] Read more.
The buff-colored layer separating the plasma from red blood cells (RBCs) in centrifuged blood was named the “buffy coat” in the late 19th century. The division of platelets (PLTs) and leukocytes (WBCs) between the buffy coat, plasma, and RBC layers in centrifuged blood has not been described before. In this study, we centrifuged 8.5 mL anticoagulated blood samples at 1000× g for 1, 2, 3, 5, 10, and 20 min. We then divided each sample into ten layers and analyzed each layer for cellular composition and mean platelet volume (MPV). Our results show that even after 20 min of centrifugation, about 15% of platelets remain in the plasma layers and 65% in the RBC layers. We found that the platelet count achieved from aspiration of 1 mL volume was optimal, with aspiration beginning 1/2 mL below the buffy coat and extending 1/2 mL above the buffy coat rather than beginning at the buffy coat itself and aspirating only plasma. Using this method of aspiration, we found that the total platelet count means reached a maximum in the 1 mL around the buffy coat after only 5 min of centrifugation. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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9 pages, 517 KiB  
Communication
Retrospective Analysis of Responders and Impaired Patients with Knee Osteoarthritis Treated with Two Consecutive Injections of Very Pure Platelet-Rich Plasma (PRP)
by Alain Silvestre, Pierre-Francois Lintingre, Lionel Pesquer, Philippe Meyer, Marie-Hélène Moreau-Durieux and Benjamin Dallaudiére
Bioengineering 2023, 10(8), 922; https://doi.org/10.3390/bioengineering10080922 - 3 Aug 2023
Cited by 3 | Viewed by 2048
Abstract
Objectives: To assess the effectiveness of two consecutive intraarticular injections of PRP to treat knee osteoarthritis (KOA), discriminating between responders and impaired patients. Methods: This retrospective study included 73 consecutive patients who were referred for two intra-articular PRP injections (one week apart) for [...] Read more.
Objectives: To assess the effectiveness of two consecutive intraarticular injections of PRP to treat knee osteoarthritis (KOA), discriminating between responders and impaired patients. Methods: This retrospective study included 73 consecutive patients who were referred for two intra-articular PRP injections (one week apart) for treating symptomatic moderate/severe KOA. Biological characterization of the PRP, including platelets, leukocytes and erythrocytes, was evaluated. Patient’s subjective symptoms were recorded before the treatment and 1 year after the second injection using pain VAS and WOMAC scores. Responders were defined by an improvement of 10 points on WOMAC. Results: At a 1-year follow up, we found 36 (49.3%) patients who fulfilled the criteria of responders, and 21 (28.8%) patients were impaired. A statistically and clinically significant global improvement of −29.2 ± 14.3 (p < 0.001) points in WOMAC score was observed 1 year after treatment in the responder group, with a higher response rate in patients with KL 2 (57.7%) compared to KL IV (28.6%). The percentage of patients with KL IV was higher in the impaired group (48.0%) compared to the responders (16.6%). As expected, the evaluation of the functionality of the knee in the impaired group indicates that it significantly worsened after one year from treatment (p = 0.027). However, the average pain score remained stable with no significant differences after 1 year (p = 0.843). No clinical complications or severe adverse events after the PRP injections were reported. Conclusion: The present study suggests that two intra-articular injections of 10 mL of very pure PRP provide pain and functional improvement in symptomatic KOA. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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14 pages, 3342 KiB  
Article
Mechanism of Pulp Regeneration Based on Concentrated Growth Factors Regulating Cell Differentiation
by Sijing Yu, Yi Zheng, Qiang Guo, Wenxu Li, Ling Ye and Bo Gao
Bioengineering 2023, 10(5), 513; https://doi.org/10.3390/bioengineering10050513 - 25 Apr 2023
Cited by 4 | Viewed by 2248
Abstract
Concentrated growth factors (CGF) is the newest generation platelet concentrate product, which has been reported to promote the proliferation and differentiation of human dental pulp cells (hDPCs). However, the effect of liquid phase of CGF (LPCGF) has not been reported. This study was [...] Read more.
Concentrated growth factors (CGF) is the newest generation platelet concentrate product, which has been reported to promote the proliferation and differentiation of human dental pulp cells (hDPCs). However, the effect of liquid phase of CGF (LPCGF) has not been reported. This study was aimed to evaluate the influence of LPCGF on the biological properties of hDPCs, and to explore the in vivo mechanism of dental pulp regeneration based on the hDPCs-LPCGF complex transplantation. It was found that LPCGF could promote the proliferation, migration and odontogenic differentiation of hDPCs, and 25% LPCGF induced the most mineralization nodule formation and the highest DSPP gene expression. The heterotopic transplantation of the hDPCs-LPCGF complex resulted in the formation of regenerative pulp tissue with newly formed dentin, neovascularization and nerve-like tissue. Together, these findings provide key data on the effect of LPCGF on the proliferation, migration, odontogenic/osteogenic differentiation of hDPCs, and the in vivo mechanism of hDPCs-LPCGF complex autologous transplantation in pulp regeneration therapy. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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22 pages, 3124 KiB  
Article
Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital
by Patrick Sebbagh, Nathalie Hirt-Burri, Corinne Scaletta, Philippe Abdel-Sayed, Wassim Raffoul, Vincent Gremeaux, Alexis Laurent, Lee Ann Applegate and Gerald Gremion
Bioengineering 2023, 10(4), 409; https://doi.org/10.3390/bioengineering10040409 - 25 Mar 2023
Cited by 8 | Viewed by 2392
Abstract
Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite [...] Read more.
Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite for sound and homogeneous clinical efficacy evaluation. This retrospective study (2013–2020) considered the standardized GMP manufacturing and sports medicine-related clinical use of autologous PRP for tendinopathies at the Lausanne University Hospital (Lausanne, Switzerland). This study included 48 patients (18–86 years of age, with a mean age of 43.4 years, and various physical activity levels), and the related PRP manufacturing records indicated a platelet concentration factor most frequently in the range of 2.0–2.5. The clinical follow-up showed that 61% of the patients reported favorable efficacy outcomes (full return to activity, with pain disappearance) following a single ultrasound-guided autologous PRP injection, whereas 36% of the patients required two PRP injections. No significant relationship was found between platelet concentration factor values in PRP preparations and clinical efficacy endpoints of the intervention. The results were in line with published reports on tendinopathy management in sports medicine, wherein the efficacy of low-concentration orthobiologic interventions appears to be unrelated to sport activity levels or to patient age and gender. Overall, this study confirmed the effectiveness of standardized autologous PRP preparations for tendinopathies in sports medicine. The results were discussed in light of the critical importance of protocol standardization for both PRP manufacturing and clinical administration to reduce biological material variability (platelet concentrations) and to enhance the robustness of clinical interventions (comparability of efficacy/patient improvement). Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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20 pages, 844 KiB  
Article
Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine
by Patrick Sebbagh, Alessandro Cannone, Gerald Gremion, Vincent Gremeaux, Wassim Raffoul, Nathalie Hirt-Burri, Murielle Michetti, Philippe Abdel-Sayed, Alexis Laurent, Nathalie Wardé and Lee Ann Applegate
Bioengineering 2023, 10(3), 292; https://doi.org/10.3390/bioengineering10030292 - 24 Feb 2023
Cited by 14 | Viewed by 4411
Abstract
Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in [...] Read more.
Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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Review

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18 pages, 1980 KiB  
Review
Standardization of Animal Models and Techniques for Platelet-Rich Fibrin Production: A Narrative Review and Guideline
by Carlos Fernando Mourão, Adam Lowenstein, Rafael Coutinho Mello-Machado, Shahram Ghanaati, Nelson Pinto, Tomoyuki Kawase, Gutemberg Gomes Alves and Michel Reis Messora
Bioengineering 2023, 10(4), 482; https://doi.org/10.3390/bioengineering10040482 - 17 Apr 2023
Cited by 9 | Viewed by 3513
Abstract
Experimental research is critical for advancing medical knowledge and enhancing patient outcomes, including in vitro and in vivo preclinical assessments. Platelet-rich fibrin (PRF) is a blood by-product that has garnered attention in the medical and dental fields due to its potential for tissue [...] Read more.
Experimental research is critical for advancing medical knowledge and enhancing patient outcomes, including in vitro and in vivo preclinical assessments. Platelet-rich fibrin (PRF) is a blood by-product that has garnered attention in the medical and dental fields due to its potential for tissue regeneration and wound healing. Animal models, such as rabbits and rats, have been used to produce PRF and examine its properties and applications. PRF has demonstrated potential in the dental and medical fields for reducing inflammation, promoting tissue repair, and accelerating wound healing. This narrative review aims to compare existing evidence and provide guidelines for PRF animal research, emphasizing the importance of standardizing animal models, following ethical considerations, and maintaining transparency and accountability. The authors highlight the necessity to use the correct relative centrifugal force (RCF), standardize centrifugal calibration, and report detailed information about blood collection and centrifuge parameters for reproducible results. Standardizing animal models and techniques is crucial for narrowing the gap between laboratory research and clinical applications, ultimately enhancing the translation of findings from bench to bedside. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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30 pages, 2465 KiB  
Review
The Top 100 Most Cited Articles on Platelet-Rich Plasma Use in Regenerative Medicine—A Bibliometric Analysis—From the ESSKA Orthobiologic Initiative
by Anouck Coulange Zavarro, Laura De Girolamo, Lior Laver, Mikel Sánchez, Thomas Tischer, Giuseppe Filardo, Florence Sabatier and Jérémy Magalon
Bioengineering 2022, 9(10), 580; https://doi.org/10.3390/bioengineering9100580 - 19 Oct 2022
Cited by 15 | Viewed by 3177
Abstract
Over the past few decades, more and more articles about platelet-rich plasma (PRP) use in regenerative medicine have been published. The aim of this study was to determine which articles have been most influential in this field by identifying and analyzing the characteristics [...] Read more.
Over the past few decades, more and more articles about platelet-rich plasma (PRP) use in regenerative medicine have been published. The aim of this study was to determine which articles have been most influential in this field by identifying and analyzing the characteristics of the 100 most cited articles. Articles on the use of PRP in regenerative medicine were identified via the Thomson ISI Web of Science database. A majority of the articles originated from the USA (36%). The top journal in terms of number of articles was American Journal of Sports Medicine (12%). Musculoskeletal system and orthopedics (54%) were the most popular fields of applications. Preclinical studies were the most represented study type, from which only 8 from 46 (17.4%) provided a complete numerical description of the injected product. Analysis showed a time-dependent trend of increasing quality of the clinical studies (p = 0.004), although none of them provided a complete biological characterization of the injected PRP. This study demonstrated that the use of PRP in regenerative medicine is a growing and popular area of research, mainly focused on orthopedic applications. Studies on PRP-derived exosomes, biological characterization, and correlation with clinical results might be areas of future trends. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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Other

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16 pages, 660 KiB  
Perspective
Anti-Aging Potential of Platelet Rich Plasma (PRP): Evidence from Osteoarthritis (OA) and Applications in Senescence and Inflammaging
by James Vun, Neelam Iqbal, Elena Jones and Payal Ganguly
Bioengineering 2023, 10(8), 987; https://doi.org/10.3390/bioengineering10080987 - 21 Aug 2023
Cited by 6 | Viewed by 3501
Abstract
Aging and age-related changes impact the quality of life (QOL) in elderly with a decline in movement, cognitive abilities and increased vulnerability towards age-related diseases (ARDs). One of the key contributing factors is cellular senescence, which is triggered majorly by DNA damage response [...] Read more.
Aging and age-related changes impact the quality of life (QOL) in elderly with a decline in movement, cognitive abilities and increased vulnerability towards age-related diseases (ARDs). One of the key contributing factors is cellular senescence, which is triggered majorly by DNA damage response (DDR). Accumulated senescent cells (SCs) release senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines, matrix metalloproteinases (MMPs), lipids and chemokines that are detrimental to the surrounding tissues. Chronic low-grade inflammation in the elderly or inflammaging is also associated with cellular senescence and contributes to ARDs. The literature from the last decade has recorded the use of platelet rich plasma (PRP) to combat senescence and inflammation, alleviate pain as an analgesic, promote tissue regeneration and repair via angiogenesis—all of which are essential in anti-aging and tissue regeneration strategies. In the last few decades, platelet-rich plasma (PRP) has been used as an anti-aging treatment option for dermatological applications and with great interest in tissue regeneration for orthopaedic applications, especially in osteoarthritis (OA). In this exploration, we connect the intricate relationship between aging, ARDs, senescence and inflammation and delve into PRP’s properties and potential benefits. We conduct a comparative review of the current literature on PRP treatment strategies, paying particular attention to the instances strongly linked to ARDs. Finally, upon careful consideration of this interconnected information in the context of aging, we suggest a prospective role for PRP in developing anti-aging therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Autologous PRP Therapy)
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