Cascades technology has produced remarkable results to date.
There are over 40 peer reviewed studies conducted on our proprietary technology and products.
To learn more about the benefits of Cascades platelet-rich fibrin matrix to speed and improve the quality of chronic wound healing, a sample library is provided below along with a brief set of topics to support your personal navigation.
Here are a select few for your review and information.
Diabetic Foot Ulcers: 1
Venous Leg Ulcers: 3
Chronic Ulcers: 2,3
Other: Wound Healing, Growth Factors, Tissue Regeneration, Bone Growth, Orthopedic: 4,5,6,7,8,9,10,11,12
1. Abs. #90 Wound Healing Society Meeting (May 1, 2007) Clinical Treatments Session #53 Evaluation of an Autologous Platelet Rich Fibrin Matrix Technology for Diabetic Foot Ulcer Treatment
Christine Gosch, DPM, Alan Zeichner, DPM, Richard Carroll, PhD, and Jack Bois, DPM
Diabetic foot ulcers that heal slowly can be an increased risk for limb amputation. Improvements in the diabetic patient’s foot care gives health care providers more options in wound management. Use of an autologous platelet rich fibrin matrix (PRFM) can provide a convenient and safe addition to current practice methods. We evaluated a PRFM technology (Cascade® FIBRINET™) which uses a convenient blood collection and platelet separation technology based on evacuated blood collection tubes. The technology also allows flexibility in the volume of blood collected and the form of the PRFM. Depending on the situation, the technology can provide a PRFM gel or a PRFM membrane. No exogenous thrombin is required for platelet activation or clot formation. The purpose of this evaluation was to determine the clinical benefit of the technology for the treatment of non-healing diabetic foot ulcers. Diabetic foot ulcer patients attending a Podiatry clinic were screened and four were selected who met the evaluation criteria. Patients were clinically evaluated weekly and were treated with a PRFM membrane or gel every two weeks for a maximum of eight weeks, with a four week follow up. Patients in the evaluation had the target wound for 12 weeks to three years. Primary evaluation endpoint was 75% healing, with a secondary endpoint of 100% healing of the studied wound by 12 weeks. 4 of 4 patients met the primary endpoint and 3 of 4 met the secondary endpoint by 12 weeks, with mean time to complete healing of 9 weeks. Wound size before PRFM treatment ranged from 5.22 to 11.55 cm2. No treatment related serious adverse events were reported. Use of this PRFM technology provided a convenient, flexible, and easily adapted means to accelerate wound healing in diabetic foot ulcers.
2. Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation
ABSTRACT: The economic, social, and public health burden of chronic ulcers and other compromised wounds is enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis, and tissue sealing. In this study, we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely platelet-rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study, for the first time, shows the kinetics of the viability of platelet-embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The vascular endothelial growth factor released from PRFM was primarily responsible for endothelial mitogenic response via extracellular signal-regulated protein kinase activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers.
Sashwati Roy, PhD; Jason Driggs, BS; Haytham Elgharably, MD; Sabyasachi Biswas, PhD; Muna Findley, BS; Savita Khanna, PhD; Urmila Gnyawali, RN; Valerie K. Bergdall MD, PhD; Chandan K. Sen, PhD
3. Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers
ABSTRACT: A novel autologous platelet-rich fibrin matrix membrane (PRFM) was assessed for the ability to facilitate healing in patients with chronic lower-extremity ulcers. Preliminary data are presented from a prospective trial (n521). Twelve patients were identified with 17 venous leg ulcers (VLU) and nine bearing 13 nonvenous lowerextremity ulcers. Before enrollment, the patients were evaluated for vascular status and received appropriate surgical intervention to optimize arterial and venous circulatory status. None of the ulcers had responded to a variety of standard treatments from 4 months to 53 years. Initial ulcer size ranged from 0.7 to 65 cm2 (mean, 11.2 cm2). Each PRFM-treated patient received up to three applications of either a 35 or 50mm fenestrated membrane, depending on initial ulcer size. The primary endpoints were percent and rate of complete closure as measured by digital photography, computerized planimetery, and clinical examination. Patients were followed weekly for 12 weeks with a follow-up visit at 16 weeks. At each 4-week interval, the extent of healing was assessed, and those patients with > 50% reduction in wound area were allowed to continue to complete closure. Patients with < 50% closure received repeated applications. Complete closure was achieved in 66.7% of the VLU patients (64.7% of treated ulcers) in 7.1 weeks (median, 6 weeks) with an average of two applications per patient. Forty-four percent complete closure was seen with non- VLU patients (31% of treated ulcers). From the results of this small-scale pilot study, PRFM shows significant potential for closing of chronic leg ulcers.
Sean M. O’Connell, PhD1; Theresa Impeduglia, MD1; Karen Hessler, RN, BSN1; Xiu-Jie Wang, MD1; Richard J. Carroll, PhD2; Herbert Dardik, MD1
4. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review
BACKGROUND: Autologous plasma rich in platelets (PRP) is a derived blood product whose application in clinical practice is growing. A systematic review was conducted to evaluate its efficacy and safety.
STUDY DESIGN AND METHODS: A search was performed in electronic databases. Randomized controlled clinical trials (RCTs) in adult patients were included and assessed for methodologic quality. The main outcomes were “tissue regeneration” and “safety.” Relative risks (RRs) and standardized mean differences (SMDs) were calculated to show pooled estimates for these outcomes. When the results heterogeneity was more than 50 percent, a sensitivity analysis was performed.
RESULTS: Twenty RCTs were included (11 of oral and maxillofacial surgery, 7 of chronic skin ulcers, and 2 of surgery wounds). Four RCTs evaluated the depth reduction in gingival recession in chronic periodontitis; the SMD was 0.54 (95% confidence interval [CI], 0.16 to 0.92) mm, favorable to PRP. Three RCTs evaluated the clinical attachment level in chronic periodontitis; the SMD was 0.33 (95% CI, -0.71 to 1.37) mm. Six RCTs assessed the complete skin epithelialization in wound ulcers; the RR was 1.40 (95% CI, 0.85 to 2.31). Only 6 RCTs reported adverse effects without differences between groups.
CONCLUSIONS: PRP improves the gingival recession but not the clinical attachment level in chronic periodontitis. In the complete healing process of chronic skin ulcers, the results are inconclusive. There are little data about PRP safety. There are several methodologic limitations and, consequently, future research should focus on strong and well-designed RCTs that assess the efficacy and safety of PRP.
Ma José Martínez-Zapata, Arturo Martí-Carvajal, Ivan Solà, Ignasi Bolibar, José Ángel Expósito, Luciano Rodriguez, and Joan García
5. Growth Factor Release within Liquid and Solid PRF
Abstract: Aim: The purpose of this study was to obtain data concerning growth factor release within liquid and solid platelet-rich fibrin (PRF) matrices and to estimate the amount of potential interindividual variations as a basis for further preclinical and clinical trials. Therefore, we aimed to determine possible differences in the release of growth factors between liquid and solid PRF. Materials and Methods: Blood samples obtained from four subjects were processed to both liquid and solid PRF matrices using a standard centrifugation protocol. Five growth factors (vascular endothelial growth factor, VEGF; epidermal growth factor, EGF; platelet-derived growth factor-BB, PDGF-BB; transforming growth factor-_1, TGF-_1; and matrix metallopeptidase 9, MMP-9) have been evaluated at six time points by ELISA over a total observation period of 10 days (1 h, 7 h, 1 d, 2 d, 7 d, and 10 d).
Results: Growth factor release could be measured in all samples at each time point. Comparing liquid and solid PRF matrices, no significant differences were detected (p > 0.05). The mean release of VEGF, TGF_-1, PDGF-BB, and MMP-9 raised to a peak at time point five (day 7) in both liquid and solid PRF matrices. VEGF release was lower in liquid PRF than in solid PRF, whereas those of PDGF-BB and MMP-9 were higher in liquid PRF than in solid PRF at all time points. EGF had its peak release already at time point two after 7 h in liquid and solid matrices (hour 7 EGF solid: mean = 180 pg/mL, SD = 81; EGF liquid: mean = 218 pg/mL, SD = 64), declined rapidly until day 2, and had a second slight peak on day 7 in both groups (day 7 EGF solid: mean = 182 pg/mL, SD = 189; EGF liquid: mean = 81 pg/mL, SD = 70). Conclusions: This study detected growth factor release within liquid and solid PRF matrices with little variations. Further preclinical trials are needed to precisely analyze the growth factor release in larger samples and to better understand their effects on wound healing in different clinical indications.
Katharina Zwittnig 1,† , Barbara Kirnbauer 1,†, Norbert Jakse 1, Peter Schlenke 2 , Irene Mischak 1, Shahram Ghanaati 3 , Sarah Al-Maawi 3, Dániel Végh 1,4 , Michael Payer 1,*,‡ and Tomislav A. Zrnc 5,‡
6. Platelet-Rich Plasma and Platelet Gel: A Review
Abstract: Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and plateletpoor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many welldesigned scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, plateletrich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented.
Keywords: platelets, platelet-rich plasma, platelet gel, platelet growth factors, thrombin. JECT. 2006;38:174–187
Peter A.M. Everts, EKP, ECCP;* Johannes T.A. Knape, MD, PhD;† Gernot Weibrich, MD, DDS, PhD;‡, Jacques P.A.M. Schönberger, MD, PhD;§ Johannes Hoffmann, PhD;¶ Eddy P. Overdevest, EKP, ECCP;* Henk A.M. Box, EKP, ECCP;* André van Zundert, MD, PhD, FRCA**
7. Platelet-Rich Plasma in Chronic Wound Management:A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Abstract: Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic literature search was performed in four databases. Randomized clinical trials reporting on patients with chronic wounds treated with platelet-rich plasma (PRP) were included, comparing PRP with conventional ulcer therapy. We pooled the data using the random effects model. Our primary outcome was the change in wound size. Results: Our systematic search provided 2688 articles, and we identified 48 eligible studies after the selection and citation search. Thirty-three study groups of 29 RCTs with a total of 2198 wounds showed that the odds for complete closure were significantly higher in the PRP group than in the control group (OR = 5.32; CI: 3.37; 8.40; I2 = 58%). Conclusions: PRP is a safe and effective modality to enhance wound healing. By implementing it in clinical practice, platelet-rich plasma could become a widely used, valuable tool as it could not only improve patients’ quality of life but also decrease the healthcare burden of wound management.
Fanni Adél Meznerics 1,2, Péter Fehérvári 2,3, Fanni Dembrovszky 2,4, Kata Dorottya Kovács 1, Lajos Vince Kemény 1,5, Dezs˝o Csupor 2,4,6, Péter Hegyi 2,4,7 and András Bánvölgyi 1,*
8. The usefulness of platelet-rich plasma to manage skin wounds: A meta-analysis
Abstract: A meta-analysis investigation to measure the usefulness of platelet-rich plasma (PRP) to manage skin wounds (SWs). A comprehensive literature inspection till February 2023 was applied and 1349 interrelated investigations were reviewed. The 22 chosen investigations enclosed animals’ SWs were in the chosen investigations’ starting point, 3348 of them were treated with PRP, and 2259 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the usefulness of PRP to manage SWs by the dichotomous and continuous approaches and a fixed or random model. PRP significantly higher percent of decreases in open wound area (OWA) (MD, 10.07; 95% CI, 6.55-13.59, P < 0.001), and lower healing time (HT) (MD, _6.31; 95% CI, _10.69 to _1.93, P = 0.005) compared to control in animals’ SWs. PRP had a significantly higher percent of decreases in OWA and lower HT compared to control in animals’ SWs. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.
Liqiao Chi | Qiang Wang | Wenjun Zhong | Xinfeng Pan | Yuanyuan Li
9. A Recently Developed Bifacial Platelet-rich Fibrin Matrix
Abstract: Platelet-rich plasma (PRP) is used clinically in liquid or gel form to promote tissue repair. Because of the poor mechanical properties, conventional PRP is often difficult to handle when used in clinical settings and requires secure implantation in a specific site, otherwise when released growth factors could be washed out during an operation. In this study, we analyzed the end product of a recently developed commercially available system (FIBRINET®), which is a dense pliable, platelet-rich fibrin matrix (PRFM). We characterized the mechanical properties of PRFM and tested whether PRFM releases growth factors and whether released factors induce the proliferation of mesenchymal stem cells (MSC). Mechanical properties as well as platelet distribution were evaluated in PRFM. PRFM demonstrated robust mechanical properties, with a tear elastic modulus of 937.3 + 314.6 kPa, stress at a break of 1476.0 + 526.3 kPa, and an elongation at break of 146.3 + 33.8 %. PRFM maintained its mechanical properties throughout the testing process. Microscopic observations showed that the platelets were localized on one side of the matrix. Elevated levels of PDGF-AA, PDGF-AB, EGF, VEGF, bFGF and TGF-β1 were measured in the day 1-conditioned media (CM) of PRFM and growth factor levels decreased thereafter. BMP2 and BMP7 were not detectable. MSC culture media supplemented with 20% PRFM-CM stimulated MSC cell proliferation; at 24 and 48 hours the induction of the proliferation was significantly greater than the induction obtained with media supplemented with 20% foetal bovine serum. The present study shows that the production of a dense, physically robust PRFM made through high-speed centrifugation of intact platelets and fibrin in the absence of exogenous thrombin yields a potential tool for accelerating tissue repair.
Lucarelli1*, R. Beretta2, B. Dozza1, P.L. Tazzari3, S.M. O’Connell4, F. Ricci3, M. Pierini1,
Squarzoni5, P.P. Pagliaro3, E.I. Oprita6, and D. Donati1
10. The Effect of Thrombin Activation of Platelet-Rich Plasma on Demineralized Bone Matrix Osteoinductivity
Background: Demineralized bone matrix is an osteoinductive and osteoconductive material that is often used in orthopaedic surgery to induce bone formation. Autologous platelet-rich plasma, which contains proliferative and chemoattractant growth factors, has been used as a demineralized bone matrix adjuvant with mixed results. One variable during clinical use appears to be whether the platelet-rich plasma is activated with thrombin or is implanted in a liquid form with intact platelets. The objective of the present study was to determine if platelet-rich plasma can increase the osteoinductivity of demineralized bone matrix when used without thrombin activation.
Methods: The bioactivity of the demineralized bone matrix was evaluated in vitro by determining alkaline phosphatase production by C2C12 myoblast cells. The effect of thrombin activation on platelet-rich plasma was studied in vitro by evaluating osteosarcoma and bone marrow stromal cells for cell number and transforming growth factor-b1 activation. Demineralized bone matrices supplemented with platelet-rich plasma, with or without thrombin activation, were im- planted intramuscularly in athymic rats and were examined at fourteen, twenty-eight, and fifty-six days. Histological samples were analyzed for osteogenesis and chondrogenesis. Osteogenesis was further characterized on the basis of alkaline phosphatase activity.
Results: In vitro, thrombin triggered an immediate release of growth factors from the platelet-rich plasma, and the platelet-rich plasma increased the number of both osteosarcoma and stromal cells in a dose-dependent manner. Thrombin activation of the platelet-rich plasma eliminated such stimulatory effects. In vivo, the platelet-rich plasma stimulated chondrogenesis on Day 14 and osteogenesis on Days 28 and 56, whereas thrombin-activated platelet-rich plasma acted as an inhibitor of such events. In addition, inflammatory cells were detected in demineralized bone matrix samples that were mixed with thrombin-activated platelet-rich plasma. These cells were not present in matrix mixed with platelet-rich plasma alone.
Conclusions: Platelet-rich plasma significantly increased in vivo demineralized bone matrix osteoinductivity only when used without thrombin activation.
Bo Han, Jennifer Woodell-May, Michael Ponticiello, Zhi Yang and Marcel Nimni
J Bone Joint Surg Am. 2009;91:1459-1470. doi:10.2106/JBJS.H.00246
11. Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation
ABSTRACT: The economic, social, and public health burden of chronic ulcers and other compromised wounds is enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis, and tissue sealing. In this study, we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely platelet-rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study, for the first time, shows the kinetics of the viability of platelet-embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The vascular endothelial growth factor released from PRFM was primarily responsible for endothelial mitogenic response via extracellular signal-regulated protein kinase activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers.
Sashwati Roy, PhD; Jason Driggs, BS; Haytham Elgharably, MD; Sabyasachi Biswas, PhD;
Muna Findley, BS; Savita Khanna, PhD; Urmila Gnyawali, RN; Valerie K. Bergdall MD, PhD;
Chandan K. Sen, PhD
12. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review
BACKGROUND: Autologous plasma rich in platelets (PRP) is a derived blood product whose application in clinical practice is growing. A systematic review was conducted to evaluate its efficacy and safety.
STUDY DESIGN AND METHODS: A search was per-formed in electronic databases. Randomized controlled clinical trials (RCTs) in adult patients were included and assessed for methodologic quality. The main outcomes were “tissue regeneration” and “safety.” Relative risks (RRs) and standardized mean differences (SMDs) were calculated to show pooled estimates for these out- comes. When the results heterogeneity was more than 50 percent, a sensitivity analysis was performed.
RESULTS: Twenty RCTs were included (11 of oral and maxillofacial surgery, 7 of chronic skin ulcers, and 2 of surgery wounds). Four RCTs evaluated the depth reduction in gingival recession in chronic periodontitis; the SMD was 0.54 (95% confidence interval [CI], 0.16 to 0.92) mm, favorable to PRP. Three RCTs evaluated the clinical attachment level in chronic periodontitis; the SMD was 0.33 (95% CI, – 0.71 to 1.37) mm. Six RCTs assessed the complete skin epithelialization in wound ulcers; the RR was 1.40 (95% CI, 0.85 to 2.31). Only 6 RCTs reported adverse effects without differences between groups.
CONCLUSIONS: PRP improves the gingival recession but not the clinical attachment level in chronic periodontitis. In the complete healing process of chronic skin ulcers, the results are inconclusive. There are little data about PRP safety. There are several methodologic limitations and, consequently, future research should focus on strong and well-designed RCTs that assess the efficacy and safety of PRP.
Ma José Martínez-Zapata, Arturo Martí-Carvajal, Ivan Solà, Ignasi Bolibar, José Ángel Expósito,
Luciano Rodriguez, and Joan García