Unique heterologous fibrin biopolymer with hemostatic, adhesive, sealant, scaffold and drug delivery properties: a systematic review

Abstract

Fibrin biopolymers, previously referred as "fibrin glue" or "fibrin sealants", are natural biomaterials with diverse applications on health. They have hemostatic, adhesive, sealant, scaffold and drug delivery properties and have become widely used in medical and dental procedures. Historically, these biomaterials are produced from human fibrinogen and human or animal thrombin, and the possibility of transmission of infectious diseases by human blood is not ruled out. In the 1990s, to overcome this problem, a new heterologous biomaterial composed of a thrombin-like enzyme purified from Crotalus durissus terrificus venom and a cryoprecipitate rich in fibrinogen extracted from buffaloes Bubalus bubalis blood has been proposed. Therefore, a systematic review of studies on exclusively heterologous fibrin sealants published between 1989 and 2018 was carried out using the following databases: PubMed, SciELO and Google Scholar. The keyword used was "heterologous fibrin sealant". The search resulted in 35 scientific papers in PubMed, four in SciELO and 674 in Google Scholar. After applying the inclusion/exclusion criteria and complete reading of the articles, 30 studies were selected, which formed the basis of this systematic review. It has been observed that the only completely heterologous sealant is the one produced by CEVAP/UNESP. This heterologous biopolymer is proven effective by several studies published in refereed scientific journals. In addition, clinical trials phase I/II for the treatment of chronic venous ulcers authorized by the Brazilian Health Regulatory Agency (ANVISA) were completed. Preliminary results have indicated a safe and promising effective product. Phase III clinical trials will be proposed and required to validate these preliminary findings.

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

“…Initially called as heterologous fibrin sealant (HFS), this bioproduct, derived from snake venom produced by the CEVAP, was used in the recovery of venous ulcers [10,55,56] and as a glue for injured nerves [57]. Next, new experiments showed more advantages of the sealant, such as the ability to act as a scaffold for stem cells [30] or biomaterials [15][16][17]50,58] and as a new medication administration system [9]. Considering that the use of this bioproduct goes beyond its adhesive capabilities, its nomenclature has been reconsidered and has recently been called "fibrin biopolymer", but there are still not many studies on the osteogenic potential of HFB.…”

“…In addition, researchers are looking for an ideal scaffold to be used in conjunction with bovine bone matrix (BM). In this context, fibrin sealant stands out as an aid in granule adhesion, in the formation of a stable fibrin network and in the maintenance of the medium as a support for cell growth [6][7][8][9]. Commercial sealants are all homologous, that is, made from human blood components, which makes them extremely expensive due to the scarcity of raw materials for production.…”

“…To overcome these challenges, the Center for the Study of Venoms and Venomous Animals (CEVAP) from São Paulo State University (UNESP), Sao Paulo, Brazil, has been studying and developing heterologous fibrin biopolymer (HFB) from animal origin materials since the 1990s. This heterologous biomaterial is biocompatible, having hemostatic, adhesive, sealant, scaffold and drug delivery properties [9][10][11]. This bioproduct is being successfully tested in reconstruction processes when applied to various tissues [6,[12][13][14][15].…”

“…Considering the absence of previous studies that have used the unique heterologous fibrin biopolymer derived from snake venom in the world, (HFB) [9], associated with bone substitute of proven grafting quality [26,27], with results similar to the gold standard (ABG) [28], it was decided to conduct this research in noncritical defects of rat tibia in order to evaluate the therapeutic potential of the combination of these products, associating a recent PBMT protocol, already demonstrated in the literature as promising to treat bone defects [8,16], but not yet explored along the lines of this research.…”

Clinical potential in modern medicine of fibrin glues as drug delivery system

“…A new fi brin sealant, currently called fi brin biopolymer due to its diversity of applications and properties, was developed in Brazil by a group of researchers from CEVAP (Center of the Studies of Venoms and Venomous Animals -UNESP Botucatu, SP) without the presence of human blood. This bioproduct has been shown to be effective in a variety of preclinical and clinical situations with therapeutic potential such as repair of nerve damage [13][14][15][16][17][18], correction of bone defects [8,[19][20][21], treatment of venous ulcers [22] and stem cell scaffolds [23].…”