CASCADE PAPERS
A Recently Developed Bifacial PRF Matrix - Lucarelli - 2010
PRFM kit produces a 210-fold higher concentration of platelets when compared to the initial input of whole blood.
Platelets observed in PRFM mostly have a lenticular shape that is consistent with an inactivated state.
Growth factors released from the PRFM are active and sustain the proliferative potential of Mesenchymal Stem Cells.
PRFM has an average elastic modulus of 937 kPa. This is comparable to arterial tissue and represents approximately 50% of the stiffness of intact human skin.
Lucarelli E, Beretta R, Dozza B, Tazzari PL, O’Connel SM, Ricci F, Pierini M, Squarzoni S, Pagliaro PP, Oprita EI, Donati D. A recently developed bifacial platelet-rich fibrin matrix. Eur Cell Mater. 2010 Jul 1;20:13-23.
A Recently Developed Bifacial PRF Matrix - Lucarelli - 2010
PRFM kit produces a 210-fold higher concentration of platelets when compared to the initial input of whole blood.
Platelets observed in PRFM mostly have a lenticular shape that is consistent with an inactivated state.
Growth factors released from the PRFM are active and sustain the proliferative potential of Mesenchymal Stem Cells.
PRFM has an average elastic modulus of 937 kPa. This is comparable to arterial tissue and represents approximately 50% of the stiffness of intact human skin.
Lucarelli E, Beretta R, Dozza B, Tazzari PL, O’Connel SM, Ricci F, Pierini M, Squarzoni S, Pagliaro PP, Oprita EI, Donati D. A recently developed bifacial platelet-rich fibrin matrix. Eur Cell Mater. 2010 Jul 1;20:13-23.
Autologous Platelet‐Rich Fibrin Matrix as Cell Therapy in the Healing of Lower-Extremity Ulcers - O'Connel - 2008
12 patients, with 17 VLU, were treated with one to three PRFM applications along with appropriate standard wound care.
64.7% of VLU (66.7% of patients) treated with PRFM closed within the study period of 16 weeks, with an average of two applications per patient.
The mean time to complete closure in patients with VLU was 7.1 weeks (median 6 weeks).
No ulcer that achieved complete closure during the 16-week study reopened during the evaluation period.
Data indicated ulcers responding to the PRFM diverge rapidly (by week 3) in their progress to closure compared with ulcers that do not respond.
No treatment-associated complications or adverse reactions were observed during the 16 week study.
O’Connell SM, Impeduglia T, Hessler K, Wang XJ, Carroll RJ, Dardik H. Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers. Wound Repair Regen. 2008 Nov-Dec;16(6):749-56.
Cascade Autologous System Platelet-Rich Fibrin Matrix in the Treatment of Chronic Leg Ulcers - O'Connel - 2012
Provides an excellent review of Cascade PRFM technology, prior clinical work, and some of the literature on Cascade included in this list.
O’Connell SM, Hessler K, Dardik H. Cascade® Autologous System Platelet-Rich Fibrin Matrix in the Treatment of Chronic Leg Ulcers. Adv Wound Care (New Rochelle). 2012 Feb;1(1):52-55.
PRFM Improves Wound Angiogenesis via Inducing Endothelial Cell Proliferation - Roy - 2011
Cascade platelet recovery, from 20 human donors, was between 35 and 95%, with a mean of 65%.
Demonstrated platelet viability, in vitro, from 100% to 60% over 7 days.
A slow and steady release of growth factors (PDGF, TGF, VEGF) from PRFM, leading to increasing concentrations, was observed in vitro.
PRFM effectively induced endothelial cell proliferation and functional blood vessels in chronic wounds in a delayed porcine model of ischemic wound angiogenesis.
VEGF released from PRFM was primarily responsible for endothelial mitogenic response.
Roy S, Driggs J, Elgharably H, Biswas S, Findley M, Khanna S, Gnyawali U, Bergdall VK, Sen CK. Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation. Wound Repair Regen. 2011 Nov;19(6):753-66.
Whitepaper 2 Exogenous Thrombin Platelet Activation - Carroll - 2006
Demonstrated that platelets isolated from blood using the Cascade system are essentially intact and inactivated.
In contrast, 5 minute exposure to 100 U/mL (U = International bovine thrombin unit) resulted in >95% activation and >65% degranulation exposed platelets.
Carroll R, Arnoczky S, Graham S, O’Connell SM. Characterization of Autologous Growth Factors in Cascade® Platelet-Rich Fibrin Matrix (PRFM). Edison, NJ: Musculoskeletal Transplant Foundation; 2006.
Whitepaper 1 Characterization of Autologous Growth Factors in Cascade PRFM - O'Connel - 2008
PRFM was cultured in vitro with media replaced at each time point (“washed-out”), so only the GFs released since the previous time point would be measured.
Platelets within the PRFM remain functionally viable and continually released all GFs within the PRFM out to 7 days, in vitro, at room temperature.
The production of five, out of the six, GFs examined exhibited an increasing rate of release out to 72 hours post blood draw. The exception is IGF-I which maintained a relatively constant level.
O’Connell S, Carroll R, Beavis A, et al. Flow Cytometric Characterization of Cascade Platelet-Rich Fibrin Matrix (PRFM); the Impact of Exogenous Thrombin on Platelet Concentrates (PC) Edison, NJ: Musculoskeletal Transplant Foundation; 2008.
REVIEWS & OTHER LITERATURE
Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review - Zapata 2009
A review of 20 Randomized Clinical Trials (RCT) utilizing PRP in oral and maxillofacial surgery, skin ulcers, and surgery wounds.
When only high quality studies were included in review of “complete ulcer epithelialization,” the results were significant and favorable to PRP.
The included studies that reported on treatment-related adverse events agreed that, overall, there were not treatment-related complications.
Martínez-Zapata MJ, Martí-Carvajal A, Solà I, Bolibar I, Angel Expósito J, Rodriguez L, García J. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion. 2009 Jan;49(1):44-56.
Platelet-Rich Plasma and Platelet Gel: A Review - Everts 2006
This review addresses a variety of uses for platelet gel, platelet anatomy and function, platelet actions in hemostasis, platelets and platelet GFs in wound healing, the role of platelets in bone growth, and platelet gel studies in humans and animals up until 2006.
After injury, platelets: become activated, change shape, spread over the site of injury (platelet aggregation), form a ‘platelet plug,’ release GF (platelet degranulation), and develop a fibrin network to reinforce the platelet plug. Later, leukocytes release cytokines to break down the fibrin network (fibrinolysis).
The wound healing process has distinctions based on the type and depth of injury. Broadly, wound healing includes hemostasis, inflammation, matrix deposition, collagen synthesis, epithelialization, and tissue remodeling.
Some key effects of GFs are to stimulate mesenchymal stem cell proliferation, promote the migration of fibroblasts, stimulate collagen production, and induce angiogenesis.
Describes which cell types produce which GFs, what cells GFs act upon in the stages of healing, and the effect the GFs have on the cells they act on.
Everts PA, Knape JT, Weibrich G, Schönberger JP, Hoffmann J, Overdevest EP, Box HA, van Zundert A. Platelet-rich plasma and platelet gel: a review. J Extra Corpor Technol. 2006 Jun;38(2):174-87.
Growth Factor Release within Liquid and Solid PRF - Zwittnig 2022
Evaluated liquid and solid PRF matrices, from the blood samples of 4 subjects, for levels of 5 GFs (VEGF, EGF, PDGF, TGF, and Matrix Metallopeptidase 9 (MMP-9)) in vitro.
All 5 growth factors were released in liquid and solid PRF at all 6 time points (1 hour, 7 hours, 1 day, 2 days, 7 days, and 10 days) with peaks at 7 days except EGF.
EGF reached a consistent level in solid PRF from 7 hours to 7 days in solid PRF versus liquid PRF where it peaked at 7 hours and then declined.
At all time points, VEGF release was higher in solid PRF than in liquid PRF, whereas PDGF-BB and MMP-9 were higher in liquid PRF than in solid PRF.
TGF and EGF were lower in solid PRF than liquid PRF within 24 hours. Thereafter, they were higher in solid PRF than liquid PRF.
Zwittnig K, Kirnbauer B, Jakse N, Schlenke P, Mischak I, Ghanaati S, Al-Maawi S, Végh D, Payer M, Zrnc TA. Growth Factor Release within Liquid and Solid PRF. J Clin Med. 2022 Aug 29;11(17):5070.
Platelet-Rich Plasma in Chronic Wound Management: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
The selection process yielded 33 study groups of 29 RCTs with a total of 2198 wounds reporting on complete closure.
Odds for complete closure were significantly higher in the PRP group than in the control group for all ulcers and subgrouping based on ulcer etiology (DFUs and VLUs).
Odds for complete closure were significantly higher in VLUs than in DFUs treated with PRP.
The selection process yielded 18 study groups of 16 RCTs with a total of 1062 wounds reporting reduction of wound area.
Studies that reported the reduction of wound area showed a significant difference between the post-treatment wound size of the PRP and the control groups.
Studies that reported healing times showed shorter healing times in the PRP groups than control groups.
Studies that reported adverse events either recorded no adverse events or no statistically significant difference between the PRP and the control groups.
The authors conclude that “Platelet-rich plasma is a safe and effective modality to enhance wound healing.”
Meznerics FA, Fehérvári P, Dembrovszky F, Kovács KD, Kemény LV, Csupor D, Hegyi P, Bánvölgyi A. Platelet-Rich Plasma in Chronic Wound Management: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Clin Med. 2022 Dec 19;11(24):7532.
MEDICAL ACRONYMS & ABBREVIATIONS GUIDE
DFU – Diabetic Foot Ulcer
VLU – Venous Leg Ulcer
RCT – Randomized Clinical Trial
GF – Growth Factors
PDGF – Platelet Derived Growth Factor
TGF – Transforming Growth Factor
VEGF – Vascular Endothelial Growth Factor
IGF – Insulin-Like Growth Factor
EGF – Epidermal Growth Factor
bFGF – Basic Fibroblast Growth Factor
