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Regenerative Therapy Using Blood-Derived Biomaterials
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Regenerative Therapy Using Blood-Derived Biomaterials

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 31252

Special Issue Editor

Dr. Tomoyuki Kawase

E-Mail Website
Guest Editor
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

Special Issue Information

Dear Colleague, 

Blood is the most easily accessible source of bioderived materials in our body. Among these blood-derived biomaterials, because of their high ability to mimic in vivo healing processes, platelet concentrates, such as PRP and its derivatives, have been widely spread and are appreciated as the most successful model in therapies for soft and hard tissue regeneration. However, we should also recognize the real current situation that their clinical application lacks sufficient basic evidence at cellular and molecular levels, and thus, their regenerative action, especially for bone regeneration, is still under controversy.

To improve their efficacy and reproducibility, we should think and work harder independently or collaboratively. Evidence-based development of novel promising blood-derived materials would be the most commonly assumed standard approach. Standardization of pre-existing preparation protocols, establishment of quality inspection methods and proposal of combinational use with other therapies could be alternative approaches. Furthermore, you may have much more exciting ideas for how to achieve this goal.

In this Special Issue, the topics of interest are not limited to the abovementioned ones. Original impactful cutting-edge research and insightful review articles regarding basic aspects of blood-derived biomaterials are highly welcome.

Dr. Tomoyuki Kawase
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Blood-derived biomaterials
  • Platelet-rich plasma
  • Platelet-rich fibrin
  • Serum albumin
  • Blood components
  • Platelet extracts
  • Preparation protocols
  • Quality assurance
  • Regenerative therapy
  • Tissue engineering

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

4 pages, 1611 KiB  
Editorial
A Strategic and Worldwide Cooperative Challenge Required for the Next Generation of Platelet Concentrates
by Tomoyuki Kawase
Int. J. Mol. Sci. 2022, 23(7), 3437; https://doi.org/10.3390/ijms23073437 - 22 Mar 2022
Cited by 6 | Viewed by 2185
Abstract
Blood-derived biomaterials, which are represented by platelet-rich plasma (PRP) or more recently by platelet-rich fibrin (PRF), have been used in regenerative therapy for almost 30 years [...] Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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Research

Jump to: Editorial, Review

16 pages, 15835 KiB  
Article
Optimization of Lyophilized Hyperacute Serum (HAS) as a Regenerative Therapeutic in Osteoarthritis
by Isabel Olmos Calvo, Olga Kuten-Pella, Karina Kramer, Ágnes Madár, Szilvia Takács, Dorottya Kardos, Diána Simon, Szabina Erdö-Bonyár, Timea Berki, Andrea De Luna, Stefan Nehrer and Zsombor Lacza
Int. J. Mol. Sci. 2021, 22(14), 7496; https://doi.org/10.3390/ijms22147496 - 13 Jul 2021
Cited by 7 | Viewed by 2948
Abstract
Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined [...] Read more.
Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration. Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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15 pages, 23407 KiB  
Article
Biologization of Pcl-Mesh Using Platelet Rich Fibrin (Prf) Enhances Its Regenerative Potential In Vitro
by Sarah Al-Maawi, Eva Dohle, Jing Lim, Paul Weigl, Swee Hin Teoh, Robert Sader and Shahram Ghanaati
Int. J. Mol. Sci. 2021, 22(4), 2159; https://doi.org/10.3390/ijms22042159 - 22 Feb 2021
Cited by 16 | Viewed by 3525
Abstract
Introduction: Resorbable synthetic scaffolds are promising for different indications, especially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative [...] Read more.
Introduction: Resorbable synthetic scaffolds are promising for different indications, especially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative capacity of biomaterials. The present study aimed to analyze whether biologization of a PCL-mesh coated using differently centrifuged Platelet rich fibrin (PRF) matrices will have a positive influence on primary human osteoblasts activity in vitro. A polymeric resorbable scaffold (Osteomesh, OsteoporeTM (OP), Singapore) was combined with differently centrifuged PRF matrices to evaluate the additional influence of this biologization concept on bone regeneration in vitro. Peripheral blood of three healthy donors was used to gain PRF matrices centrifuged either at High (710× g, 8 min) or Low (44× g, 8 min) relative centrifugal force (RCF) according to the low speed centrifugation concept (LSCC). OP-PRF constructs were cultured with pOBs. POBs cultured on the uncoated OP served as a control. After three and seven days of cultivation, cell culture supernatants were collected to analyze the pOBs activity by determining the concentrations of VEGF, TGF-β1, PDGF, OPG, IL-8, and ALP- activity. Immunofluorescence staining was used to evaluate the Osteopontin expression of pOBs. After three days, the group of OP+PRFLow+pOBs showed significantly higher expression of IL-8, TGF-ß1, PDGF, and VEGF compared to the group of OP+PRFHigh+pOBs and OP+pOBs. Similar results were observed on day 7. Moreover, OP+PRFLow+pOBs exhibited significantly higher activity of ALP compared to OP+PRFHigh+pOBs and OP+pOBs. Immunofluorescence staining showed a higher number of pOBs adherent to OP+PRFLow+pOBs compared to the groups OP+PRFHigh+pOBs and OP+pOBs. To the best of our knowledge, this study is the first to investigate the osteoblasts activity when cultured on a PRF-coated PCL-mesh in vitro. The presented results suggest that PRFLow centrifuged according to LSCC exhibits autologous blood cells and growth factors, seem to have a significant effect on osteogenesis. Thereby, the combination of OP with PRFLow showed promising results to support bone regeneration. Further in vivo studies are required to verify the results and carry out potential results for clinical translation. Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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Graphical abstract

13 pages, 2039 KiB  
Article
Effect of Oral Losartan on Orthobiologics: Implications for Platelet-Rich Plasma and Bone Marrow Concentrate—A Rabbit Study
by Gilberto Y. Nakama, Sabrina Gonzalez, Polina Matre, Xiaodong Mu, Kaitlyn E. Whitney, Hajime Utsunomiya, Justin W. Arner, Marc J. Philippon, Sudheer Ravuri and Johnny Huard
Int. J. Mol. Sci. 2020, 21(19), 7374; https://doi.org/10.3390/ijms21197374 - 6 Oct 2020
Cited by 8 | Viewed by 3476
Abstract
Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in [...] Read more.
Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03). Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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17 pages, 1287 KiB  
Article
Leucocyte-Rich Platelet-Rich Plasma Enhances Fibroblast and Extracellular Matrix Activity: Implications in Wound Healing
by Jeannie Devereaux, Narges Dargahi, Sarah Fraser, Kulmira Nurgali, Dimitrios Kiatos and Vasso Apostolopoulos
Int. J. Mol. Sci. 2020, 21(18), 6519; https://doi.org/10.3390/ijms21186519 - 6 Sep 2020
Cited by 22 | Viewed by 5721
Abstract
Background: Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of platelets and leucocytes, which are fundamental fibroblast proliferation agents. Literature has emerged that offers contradictory findings about leucocytes within PRP. Herein, we elucidated the effects of highly concentrated [...] Read more.
Background: Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of platelets and leucocytes, which are fundamental fibroblast proliferation agents. Literature has emerged that offers contradictory findings about leucocytes within PRP. Herein, we elucidated the effects of highly concentrated leucocytes and platelets on human fibroblasts. Methods: Leucocyte-rich, PRP (LR-PRP) and leucocyte-poor, platelet-poor plasma (LP-PPP) were compared to identify their effects on human fibroblasts, including cell proliferation, wound healing and extracellular matrix and adhesion molecule gene expressions. Results: The LR-PRP exhibited 1422.00 ± 317.21 × 103 platelets/µL and 16.36 ± 2.08 × 103 white blood cells/µL whilst the LP-PPP demonstrated lower concentrations of 55.33 ± 10.13 × 103 platelets/µL and 0.8 ± 0.02 × 103 white blood cells/µL. LR-PRP enhanced fibroblast cell proliferation and cell migration, and demonstrated either upregulation or down-regulation gene expression profile of the extracellular matrix and adhesion molecules. Conclusion: LR-PRP has a continuous stimulatory anabolic and ergogenic effect on human fibroblast cells. Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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13 pages, 2584 KiB  
Article
Quantitative Near-Infrared Imaging of Platelets in Platelet-Rich Fibrin (PRF) Matrices: Comparative Analysis of Bio-PRF, Leukocyte-Rich PRF, Advanced-PRF and Concentrated Growth Factors
by Hachidai Aizawa, Tetsuhiro Tsujino, Taisuke Watanabe, Kazushige Isobe, Yutaka Kitamura, Atsushi Sato, Sadahiro Yamaguchi, Hajime Okudera, Kazuhiro Okuda and Tomoyuki Kawase
Int. J. Mol. Sci. 2020, 21(12), 4426; https://doi.org/10.3390/ijms21124426 - 22 Jun 2020
Cited by 23 | Viewed by 4316
Abstract
Platelet-rich fibrin (PRF) is a fibrin matrix enriched with platelets. The PRF matrix is thought to form a steep gradient of platelet density around the region corresponding to the buffy coat in anticoagulated blood samples. However, this phenomenon has not yet been proven. [...] Read more.
Platelet-rich fibrin (PRF) is a fibrin matrix enriched with platelets. The PRF matrix is thought to form a steep gradient of platelet density around the region corresponding to the buffy coat in anticoagulated blood samples. However, this phenomenon has not yet been proven. To visualize platelet distribution in PRF in a non-invasive manner, we utilized near-infrared (NIR) imaging technology. In this study, four types of PRF matrices, bio-PRF, advanced-PRF (A-PRF), leukocyte-rich PRF (L-PRF), and concentrated growth factors (CGF) were compared. Blood samples collected from healthy, non-smoking volunteers were immediately centrifuged using four different protocols in glass tubes. The fixed PRF matrices were sagittally divided into two equal parts, and subjected to modified immunohistochemical examination. After probing with NIR dye-conjugated secondary antibody, the CD41+ platelets were visualized using an NIR imager. In L-PRF and CGF, platelets were distributed mainly on and below the distal surface, while in bio-PRF and A-PRF, platelet distribution was widespread and homogenous. Among three regions of the PRF matrices (upper, middle, and lower), no significant differences were observed. These findings suggest that platelets aggregate on polymerizing fibrin fibers and float up as a PRF matrix into the plasma fraction, amending the current “gradient” theory of platelet distribution. Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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Review

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18 pages, 1510 KiB  
Review
From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release
by Karina Egle, Ilze Salma and Arita Dubnika
Int. J. Mol. Sci. 2021, 22(21), 11553; https://doi.org/10.3390/ijms222111553 - 26 Oct 2021
Cited by 36 | Viewed by 7306
Abstract
The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility [...] Read more.
The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally. Full article
(This article belongs to the Special Issue Regenerative Therapy Using Blood-Derived Biomaterials)
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