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Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 12341

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Special Issue Editors

Dr. Tomoyuki Kawase

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Division of Oral Bioengineering, Institute of Medicine and Dentistry, Niigata University, Niigata 951-8514, Japan
Interests: platelet concentrates; regenerative dentistry; tissue engineering; quality control
Special Issues, Collections and Topics in MDPI journals

Dr. Takashi Ushiki

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Guest Editor

Department of Transfusion Medicine, Cell Therapy and Regenerative Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
Interests: platelet concentrates; regenerative medicine; transfusion; inflammatory diseases; immunology

Dr. Tomoharu Mochizuki

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Guest Editor

Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan
Interests: knee; knee arthroplasty; arthroplasty; anterior cruciate ligament; knee injuries; knee surgery; cartilage; sports injuries; biomechanics; musculoskeletal imaging

Special Issue Information

Dear Colleagues,

In this Special Issue, we would like to provide a platform to exchange your unique basic findings and concepts of platelet-rich plasma (PRP) therapy and together overcome the current difficulties faced in PRP therapy.

PRP and its derivatives of blood-derived biomaterials seem to have lost their established position as the most attractive materials for regenerative medicine. However, this analysis is based only on the number of scientific publications. Considering that PRP has been constantly or increasingly used in the fields of orthopedic surgery, plastic surgery, and esthetic surgery, PRP therapy is still accepted as the first-line treatment among many clinicians and patients. PRP therapy is considered the only option for regenerative therapy, especially in countries and regions where competing therapeutic options are expensive.

Despite these conditions, why does it look like the sun is setting on PRP therapy? Ten years ago, we proposed the necessity for standardization of PRP preparation and therapy. Several years later, we indicated the flaw of the clinical studies previously conducted and mentioned our prediction of an unavoidable decline of PRP therapy when many papers regarding clinical studies, systematic reviews, and meta-analyses have been published. However, our campaign was not widely accepted and could not change the minds of the clinicians and researchers.

The popularity of therapeutic modalities is severely influenced by many factors such as potency, cost, availability, and individual differences. However, even though a certain therapy has lost its popularity, it does not necessarily imply that it also loses its potential power. PRP therapy is currently at a deadlock. To break these current conditions, we need to swiftly update our knowledge based on scientific evidence from the molecular and cellular levels.

We handle submissions from all fields of regenerative medicine; however, submissions related to sports medicine, orthopedic surgery, and transfusion are particularly welcome.

Dr. Tomoyuki Kawase
Dr. Takashi Ushiki
Dr. Tomoharu Mochizuki
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

blood-derived biomaterial
platelet-rich plasma
autologous protein solution
mechanism
platelet
coagulation

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Published Papers (8 papers)

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Research

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16 pages, 4324 KB

Open AccessArticle

In Vitro Evaluation of the Regenerative Potential of Autologous Platelet-Rich Fibrin (PRF) on Human Primary Periodontal Ligament Cells

by Eva Dohle, Marlene Quernheim, Robert Sader and Shahram Ghanaati

Int. J. Mol. Sci. 2025, 26(19), 9459; https://doi.org/10.3390/ijms26199459 - 27 Sep 2025

Viewed by 220

Abstract

Periodontitis is a prevalent condition that leads to the destruction of periodontal tissue, making the regeneration of the periodontium a key focus in dental research. In this context, periodontal ligament cells (PDLCs) are particularly interesting due to their stem cell-like properties, including the ability to differentiate into various cell types and further contribute to tissue repair. This study aimed to isolate and characterize primary human PDLCs and examine the effects of both indirect and direct treatment with the blood concentrate platelet-rich fibrin (PRF), with particular focus on how PRF influences cell proliferation and differentiation. PDLCs were treated with PRF prepared using a low relative centrifugal force (600 rpm) either directly through a conditioned medium or indirectly using trans-well filter systems. The impact of PRF on PDLC proliferation and differentiation was assessed through viability assays, alkaline phosphatase assays, gene and protein expression analyses, and immunofluorescence. PDLCs exhibited cellular markers characteristic of stem cell-like cells. In addition, PRF treatment was found to suppress cell proliferation while concurrently promoting osteogenic differentiation and increase factors important for tissue regeneration. These effects were more pronounced when the cells were directly treated with PRF-conditioned medium compared to indirect treatment. Our findings support the hypothesis that PRF serves as a biologically active reservoir of growth factors that modulate PDLC behavior and might create a microenvironment favorable for periodontal repair. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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18 pages, 1827 KB

Open AccessArticle

Exploring the Impact of Extraplatelet Content on Fibrin-Based Scaffold Performance for Regenerative Therapies

by Daniel Marijuán-Pinel, Jon Mercader-Ruiz, Maider Beitia, Pello Sánchez, Leonor López de Dicastillo, Sergio Gonzalez, João Espregueira-Mendes, Beatriz Aizpurua, Jaime Oraá, Diego Delgado and Mikel Sánchez

Int. J. Mol. Sci. 2025, 26(13), 5967; https://doi.org/10.3390/ijms26135967 - 21 Jun 2025

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Abstract

This study investigated the impact of increased extraplatelet content on the tissue regenerative capacity of platelet-rich plasma (PRP)-derived fibrin scaffolds. Comparative analyses were performed between a “balanced protein-concentrate plasma” (BPCP) and a standard PRP (sPRP), focusing on platelet and fibrinogen content, scaffold microstructure, and functional performance. Growth factor (GF) release kinetics from the scaffolds were quantified via ELISA over 10 days, while scaffold biomechanics were evaluated through rheological testing, indentation, energy dissipation, adhesion, and assessments of coagulation dynamics, biodegradation, swelling, and retraction. Microstructural analysis was conducted using scanning electron microscopy (SEM), with fiber diameter and porosity measurements. The results demonstrated that BPCP scaffolds released significantly higher amounts of GFs and total protein, especially beyond 24 h (* p < 0.05). Despite a delayed coagulation process (** p < 0.01), BPCP scaffolds exhibited superior structural integrity and cushioning behavior (* p < 0.05). SEM revealed thicker fibers in BPCP scaffolds (**** p < 0.0001), while adhesion and biodegradation remained unaffected. Notably, BPCP scaffolds showed reduced retraction after 24 h and maintained their shape stability over two weeks without significant swelling. These findings indicate that enhancing the extraplatelet content in PRP formulations can optimize fibrin scaffold performance. Further preclinical and clinical studies are warranted to evaluate the therapeutic efficacy of BPCP-derived scaffolds in regenerative medicine. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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15 pages, 1911 KB

Open AccessArticle

Elevated IL-1β and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players

by Tomoharu Mochizuki, Takashi Ushiki, Katsuya Suzuki, Misato Sato, Hajime Ishiguro, Tatsuya Suwabe, Satoshi Watanabe, Mutsuaki Edama, Go Omori, Noriaki Yamamoto and Tomoyuki Kawase

Int. J. Mol. Sci. 2023, 24(24), 17487; https://doi.org/10.3390/ijms242417487 - 14 Dec 2023

Cited by 2 | Viewed by 2066

Abstract

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-β1 (TGFβ1), platelet factor-4 (PF4), interleukin-1β (IL-1β), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFβ1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1β and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter’s higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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14 pages, 3851 KB

Open AccessArticle

New Formulation of Platelet-Rich Plasma Enriched in Platelet and Extraplatelet Biomolecules Using Hydrogels

by Jon Mercader Ruiz, Maider Beitia, Diego Delgado, Pello Sánchez, María Jesús Arnaiz, Leonor López de Dicastillo, Fernando Benito-Lopez, Lourdes Basabe-Desmonts and Mikel Sánchez

Int. J. Mol. Sci. 2023, 24(18), 13811; https://doi.org/10.3390/ijms241813811 - 7 Sep 2023

Cited by 7 | Viewed by 2204

Abstract

Platelet-rich plasma (PRP) is an autologous biologic product used in several fields of medicine for tissue repair due to the regenerative capacity of the biomolecules of its formulation. PRP consists of a plasma with a platelet concentration higher than basal levels but with basal levels of any biomolecules present out of the platelets. Plasma contains extraplatelet biomolecules known to enhance its regenerative properties. Therefore, a PRP containing not only a higher concentration of platelets but also a higher concentration of extraplatelet biomolecules that could have a stronger regenerative performance than a standard PRP. Considering this, the aim of this work is to develop a new method to obtain PRP enriched in both platelet and extraplatelet molecules. The method is based on the absorption of the water of the plasma using hydroxyethyl acrylamide (HEAA)-based hydrogels. A plasma fraction obtained from blood, containing the basal levels of platelets and proteins, was placed in contact with the HEAA hydrogel powder to absorb half the volume of the water. The resulting plasma was characterized, and its bioactivity was analyzed in vitro. The novel PRP (nPRP) showed a platelet concentration and platelet derived growth factor (PDGF) levels similar to the standard PRP (sPRP), but the concentration of the extraplatelet growth factors IGF-1 (p < 0.0001) and HGF (p < 0.001) were significantly increased. Additionally, the cells exposed to the nPRP showed increased cell viability than those exposed to a sPRP in human dermal fibroblasts (p < 0.001) and primary chondrocytes (p < 0.01). In conclusion, this novel absorption-based method produces a PRP with novel characteristics compared to the standard PRPs, with promising in vitro results that could potentially trigger improved tissue regeneration capacity. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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15 pages, 3865 KB

Open AccessArticle

Characterization of Leukocyte- and Platelet-Rich Plasma Derived from Female Collage Athletes: A Cross-Sectional Cohort Study Focusing on Growth Factor, Inflammatory Cytokines, and Anti-Inflammatory Cytokine Levels

by Tomoharu Mochizuki, Takashi Ushiki, Katsuya Suzuki, Misato Sato, Hajime Ishiguro, Tatsuya Suwabe, Mutsuaki Edama, Go Omori, Noriaki Yamamoto and Tomoyuki Kawase

Int. J. Mol. Sci. 2023, 24(17), 13592; https://doi.org/10.3390/ijms241713592 - 2 Sep 2023

Cited by 9 | Viewed by 2260

Abstract

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as “must-check” parameters to characterize individual PRP preparations prior to clinical trials. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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14 pages, 2074 KB

Open AccessArticle

Platelets Rich Plasma Increases Antioxidant Defenses of Tenocytes via Nrf2 Signal Pathway

by Alessia Tognoloni, Desiree Bartolini, Marco Pepe, Antonio Di Meo, Ilaria Porcellato, Kubra Guidoni, Francesco Galli and Elisabetta Chiaradia

Int. J. Mol. Sci. 2023, 24(17), 13299; https://doi.org/10.3390/ijms241713299 - 27 Aug 2023

Cited by 17 | Viewed by 2247

Abstract

Tendinopathies are common disabling conditions in equine and human athletes. The etiology is still unclear, although reactive oxygen species (ROS) and oxidative stress (OS) seem to play a crucial role. In addition, OS has been implicated in the failure of tendon lesion repair. Platelet-rich plasma (PRP) is rich in growth factors that promote tissue regeneration. This is a promising therapeutic approach in tendon injury. Moreover, growing evidence has been attributed to PRP antioxidant effects that can sustain tissue healing. In this study, the potential antioxidant effects of PRP in tenocytes exposed to oxidative stress were investigated. The results demonstrated that PRP reduces protein and lipid oxidative damage and protects tenocytes from OS-induced cell death. The results also showed that PRP was able to increase nuclear levels of redox-dependent transcription factor Nrf2 and to induce some antioxidant/phase II detoxifying enzymes (superoxide dismutase 2, catalase, heme oxygenase 1, NAD(P)H oxidoreductase quinone-1, glutamate cysteine ligase catalytic subunit and glutathione, S-transferase). Moreover, PRP also increased the enzymatic activity of catalase and glutathione S-transferase. In conclusion, this study suggests that PRP could activate various cellular signaling pathways, including the Nrf2 pathway, for the restoration of tenocyte homeostasis and to promote tendon regeneration and repair following tendon injuries. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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Review

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13 pages, 403 KB

Open AccessReview

The Role of Platelet-Rich Plasma (PRP) in the Treatment of Patellofemoral Arthritis and Anterior Knee Pain: A Systematic Review

by Byron Chalidis, Charalampos Pitsilos and Vasileios Davitis

Int. J. Mol. Sci. 2025, 26(18), 9006; https://doi.org/10.3390/ijms26189006 - 16 Sep 2025

Viewed by 1161

Abstract

Patellofemoral osteoarthritis (OA) and chondromalacia patellae (CMP) are common and disabling conditions that significantly affect physical performance and quality of life. Despite the great deal of scientific research on the subject, there is limited evidence regarding the outcome of nonoperative interventional procedures. Platelet-rich plasma (PRP) has demonstrated positive results for tibiofemoral knee osteoarthritis, but its role in anterior knee pain (AKP) remains unclear. The aim of this study was to review the evidence on the efficacy (clinical and radiological) and safety of PRP in patients suffering from patellofemoral OA, CMP, and AKP. Medline/Pubmed, Web of Science, and Scopus databases were systematically searched up to June 2025 to identify all the available relevant studies. Five studies, including 146 patients, fulfilled the eligibility criteria and were included in the systematic review. Although there was a statistically significant improvement in clinical setting, radiologic evidence of cartilage regeneration was limited and uncertain. Specifically, the pooled analysis revealed an improvement of the Visual Analogue Scale from 6.7 to 2.1 (p < 0.001), the Western Ontario and McMaster Universities Osteoarthritis Index score from 24 to 10.3 (p < 0.001), the Oxford score from 35.1 to 37.4 (p < 0.001), the Kujala score from 71 to 83 (p < 0.001), and the Tegner/Lysholm score from 65.3 to 86.5 (p < 0.001). Well-designed and appropriately powered randomized trials with imaging endpoints are needed to validate the efficacy of PRP administration in PFA, CMP, and AKP and refine patient selection criteria. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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15 pages, 1838 KB

Open AccessReview

Preliminary Evidence on Intra-Articular Autologous Conditioned Serum (ACS) in Temporomandibular Joint Disorders (TMDs): A Systematic Review with a Focus on Mechanisms and Potential Application in Clinical Practice

by Marcin Pasternak, Maciej Chęciński, Kamila Chęcińska, Natalia Turosz, Izabella Chyży, Bartosz Kosiński, Klaudia Kwiatkowska, Kalina Romańczyk, Amelia Hoppe and Maciej Sikora

Int. J. Mol. Sci. 2025, 26(18), 8798; https://doi.org/10.3390/ijms26188798 - 10 Sep 2025

Viewed by 608

Abstract

Intra-articular injections form a substantial element of the temporomandibular joint disorder (TMD) therapy. Given the role played by IL-1β in pathology, the use of autologous conditioned serum (ACS) is well-founded. Despite years of effective use in different locations, data regarding the intra-articular administration of ACS in TMD is scarce, and the strategy itself is not routinely applied. This study aims to provide preliminary evidence on the therapeutic efficacy of administering intra-articular ACS in treating TMD. Patients with TMD who received intra-articular ACS were included. More invasive co-interventions, such as arthroscopy, were excluded. Final searches were conducted on 17 June 2025, using five databases (ACM, BASE, DOAJ, PubMed, and SciELO). Risk of bias was evaluated using the RoB 2 tool. The results were tabulated. Only one study met the inclusion criteria. When compared to dextrose prolotherapy in internal TMD, ACS therapy resulted in greater improvement in mouth opening, pain, and joint-sound reduction. The small sample size, head-to-head design, and limited blinding suggest a highly cautious interpretation of the findings. ACS is a promising, but still experimental, therapeutic strategy addressing critical mechanisms in TMD. However, the currently available data is insufficient to confirm the effectiveness and safety of such an approach, and further high-quality studies are needed. This study received no funding. PROSPERO registration number: CRD420251069310. Full article

(This article belongs to the Special Issue Recent Progress in Regenerative Therapy Using Blood-Derived Biomaterials)

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