PROTSMART™
Plasma Ultrafiltrator
First-class concentrator of proteins and platelets
PROTSMART™
Concept
Platelets and mononucleated cells have numerous advantages as biological products for the treatment of many pathologies.
They are easily prepared autologous products, cause minimal complications, and have a broad range of potential actions.
Platelets, mononucleated cells and the liquid portion (plasma) of PRP simultaneously release many proteins and factors with different anabolic functions that reduce inflammation and promote angiogenesis and tissue regeneration. Wound healing in response to injury involves the coordination of a large number of complex cellular and molecular events within the body.
This response is defined by the need for cells to travel to the site of injury, proliferate, form blood vessels, and, eventually, extracellular matrix (ECM) to restore both the structure and the function of the damaged tissue.
The aqueous part of PRP is plasma, which is an acellular component containing proteins that are important for tissue regeneration.
These proteins are involved in the tissue healing process and enable anti-inflammatory effects, clot stabilization, anti-microbial actions, cell-matrix adhesion, and tissue synthesis while acting overall as a ubiquitous broad-spectrum proteinase inhibitor.
These cellular processes are driven by a wide variety of proteins, growth factors, and cytokines that act to control cell functions.
One of the most important plasma cytokines is a2M.
The alpha-2-macroglobulin molecule is synthesized mainly in the liver, but also locally by macrophages, fibroblasts, and it is the largest major nonimmunoglobulin protein in plasma. Alpha 2 macroglobulin acts as an antiprotease and can inactivate an enormous variety of proteinases.
It works as an inhibitor of coagulation by inhibiting thrombin. Alpha-2-macroglobulin may act as a carrier protein because it also binds to numerous growth factors and cytokines, such as platelet-derived growth factor, basic fibroblast growth factor, TGF-β, insulin, and IL-1β.
The α2M offers great potential for the regulation of cytokine homeostasis in blood and tissue, a critical point in the pathogenesis of several diseases.
Mechanical concentration accessory,
compatible with 20 ml syringes.
α2M is known as an ubiquitous broad-spectrum proteinase inhibitor.
α2M traps the proteinases released by granu- locytes during inflammation, such as matrix metalloproteinases (MMPs).
α2M is a master inhibitor of many types of cartilage- degrading enzymes, is an exciting and potential candidate for OA treatment.
α2M may play an important role in regulating inflammatory reactions in joint diseases, not only because of its action as an inhibitor of proteases, but also because of its potential to modulate several cell types involved in joint inflammation.
α2M is also involved in the immune defense reactions
with a role of protection against toxic effects by an over production of pro-inflammatory cytokines during inflammation.
But the plasma protease inhibitor a2M is not present in sufficient concentrations to inactivate the high levels of catabolic factors found in OA synovial fluid. Findings suggest that supplemental intra-articular A2M
provides chondral protection in post-traumatic OA.
CONCENTRATION OF A2M AND ANABOLIC MOLECULES
ELIMINATION OF ALL CELL MEMBRANES
PROTSMART™
What is it for?
ProtSmart™ is a class IIa medical device, designed for plasma concentration and blood components. ProtSmart™ is a hollow capillary membrane device that can be used downstream of the blood product preparation method, in order to concentrate more platelets and plasma PRP proteins or even simply the plasma proteins of PPP. The result is a concentration of solutes over a certain molecular weight (greater than the size of the pores) on one side of the membrane, and a loss of liquids and small solutes (smaller than the size of the pores) on the other.
This step is particularly useful if you want to obtain a blood product of high concentrations in small volumes.
In fact, the three ProtSmart™ models available make it possible to obtain autologous preparations of just a few ml, with platelet and protein concentrations that even reach 4-6 times the basal concentrations in whole blood.
ProtSmart™ can concentrate PRP and PPP with a volume reduction of the order of 70-75%.
During this push phase, the pressure gradient created between the two sides of the hollow capillary membrane allows plasma water to escape from its pores.
At the end of the procedure, a simple aspiration enables recovery of the concentrated plasma, from inside the ProtSmart™ device.
This kit is designed to provide at least 6x concentration of A2M, cells and Fibrinogen Proteins.
ProtSmart™ was born from the combination of capillary membrane filtration technologies and the concentration of blood products.
Thanks to a specially developed capillary membrane morphology with an average pore size of 15,000 Da, it is possible to eliminate plasma water thus concentrating the platelets, mononucleated cell, bone marrow and growth factors like alpha 2 macroglobulins present in the plasma.
A2M also binds up pro-inflammatory molecules TNF-a, TGF-b, and IL-1b7.
While IRAP (Interleukin-1 receptor antagonist protein) is present at much higher levels in bone marrow aspirate.
PROTSMART™
Technical Features
PROTSMART™
Instructions for use
After checking the product and packaging integrity, proceed as explained below.
The concentration procedure takes place through the use of at least 1 syringe (recommended volume 20 ml) and the mechanical accessory (Fig. A) and the entire procedure is shown in the figure sequence 1-7. Fig A: Front view of the mechanical accessory with the 20 ml syringe already connected (the syringe has to be pre-filled with the fluid to be concentrated: max. loading volume for ProtSmart™ 2 is 8 ml, max loading volume for ProtSmart™ 6 is 16 ml).
Once the syringe is filled with the fluid to be concentrated, it should be connected in sterile mode with the ProtSmart™ device. The system can be then placed in the relevant slot on to the mechanical accessory for concentration.
Turn the knob until it touches the syringe plunger. Fig. B: Rear view of the mechanical accessory for concentration with the syringe of 20 ml (pre-filled) already mounted and connected. It is recommended to check the position of the 3-way stopcock at the bottom; this should be positioned to enable a one-way flow between the syringe and ProtsmartTM device. Once the whole system is assembled, fit the protective cover provided together with the mechanical accessory on the base of the same (the cover is not shown in the pictures below to facilitate understanding of the procedure).
- 1. Remove the cap on the FLL connector and open the 3-way stopcock
- 2. Gently rotate the knob of the mechanical accessory clockwise until the fluid to be concentrated fills the ProtsmartTM device.
- 3. Once the fluid reaches the top of ProtSmart™ device, without letting the fluid come out, close the 3-way stopcock at the top of the ProtSmart™ device.
- 4. Press the syringe until it is empty. During this step the waste bag connected to the ProtSmart™ device should collect the plasma water coming out of ProtSmart™ .
- 5. Close the 3-way stopcock between the syringe and ProtSmart™ at the bottom of ProtSmart™ . Then gently rotate the knob counter- clockwise in order to remove the syringe from the corresponding slot.
- 6. Open the 3-way stopcock between syringe and ProtSmart™ and then move the plunger of the syringe slowly in order to create a slight depression.
- 7. Open the 3-way stopcock at the top of the ProtSmart™
- 8. Activate the syringe to collect the whole volume of concentrated fluid from the ProtSmart™ device. Suction should be performed gently and slowly in order to avoid foaming and excessive air accumulation in the syringe. Disconnect the syringe with the concentrated liquid (2.5- 3ml) for ProtSmart™ 2, (3.5-4) ml for ProtSmart™ 4 and (5-6 ml) for ProtSmart™ 6.
USE RANGE
MAXILLOFACIAL AND ODONTOSTOMATIC SURGERY
Bone and soft tissue regeneration
PLASTIC AND AESTHETIC MEDICINE
Anti-aging, bio-revitalization and biological filler
ORTHOPEDICS AND SPORT MEDICINE
Musculo-skeletal iniuries, osteoarthrosis, tendonopathy cartilage regeneration
VASCULAR SURGERY
Acute and chronic ulcers
DERMATOLOGY
Scars, alopecia and hair transplantation
GYNECOLOGY AND UROLOGY
Scleroderma, Peyronie’s disease, erectile dysfuncion, tissue rejuvenation
PROTSMART™
Reference
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Wang et al. Identification of alpha-2- macroblobulin as a master inhibitor of cartilage-degrading factors that attenuates the progression of post traumatic osteoarthritis. Arthritis & Rheumatology 2014; 66(7): 1843-1853
Cassano et al. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin1receptor antagonist protein concentration. Knee Surg Sports Tramotol Arthrosc, 1 Feb 2016
AhmedA, et al. Alpha-2-Macroglobulin: A Physiological Guardian, Journal of cellular physiology, 2013 – Wiley
Barrientos et al., Growth factors and cytokines in wound healing. Wound Repair Regen. 16, 585–601. 2008
Karli et al. “Autologous Regenerative Therapies: Rapid Concentration of Progenitor Cells, Platelets, and Proteins at the Point-of-Care,” TERMIS annual meeting, September 2015, Boston, MA
Hegde et al. “A Prospective Comparison of 3 Approved Systems for Autologous Bone Marrow Concentration Demonstrated Nonequivalence in Progen itor Cell Number and Concentration,” J Ortho Trauma, Vol. 28, October 2014
Julia Etalain et al. An Optimized Protocol for Platelet Rich Plasma Preparation to Improve its Androgenic and Regenerative Properties. Nature: Scientific Reports (2018) 8:1513
Xie et al. Biology of platelet-rich plasma and its clinical application in cartilage repair, Arthritis Research and Therapy 2014, 16:204
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Ziegler CG, Sloun RV, Gonzalez S, et al. Characterization of growth factors, cytokines, and chemokines in bone marrow concentrate and platelet-rich plasma. Am J Sport Med 2019; 47: 2174-2187
Nurden AT. The biology of the platelet with special reference to inflammation, wound healing and immunity. Front Biosci 2018; 23: 726-751
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Protein-enriched Platelet-Rich Plasma (PEFPRP) a NewProducts for Tissue Regeneration Developed Through the Ultrafiltration of PRP – Preclinical Study Laura Mazzucco, Valeria Balbo1, Simona Martinotti, Elia Ranzato, Mauro Patrone, Marcello Manfredi2, Roberto Guaschino Frontiers 2021
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Baltzer A et al (2013): A new treatment for hip osteoarthritis: clinical evidence for the efficacy of autologous conditioned serum; Orthopedic Reviews 2013, 5:e13: 59-64
Baselga GEJ, Hernández Trillos PM (2015): Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study. PLOS One 2015 Dec, 28:10(12)
Godek P (2016): Use of Autologous Serum in Treatment of Lumbar Radiculopathy Pain. Pilot Study. Orthop. Traumatol. Rehabil. 2016 Jan -Feb; 18(1):11-20
