Fibrin biopolymer as scaffold candidate to treat bone defects in rats

Abstract

Background: Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs.Methods: Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis.Results:It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation.Conclusions:FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering.

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

“…The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [ 75 ]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [ 31 , 76 , 77 ], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [ 78 - 82 ].…”

“…The insertion of the xenogenic biomaterial, mainly with the association of another three-dimensional scaffold such as the fibrin biopolymer, creates a structured microenvironment, mainly in the central area of the defects, which prevents the invasion of soft tissues and may even reduce the need for guided bone regeneration procedures, with the addition of membranes to cover the defect [20,29,[71][72][73][74] The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [75]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [31,76,77], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [78][79][80][81][82].…”

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

“…The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [ 75 ]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [ 31 , 76 , 77 ], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [ 78 - 82 ].…”

“…The insertion of the xenogenic biomaterial, mainly with the association of another three-dimensional scaffold such as the fibrin biopolymer, creates a structured microenvironment, mainly in the central area of the defects, which prevents the invasion of soft tissues and may even reduce the need for guided bone regeneration procedures, with the addition of membranes to cover the defect [20,29,[71][72][73][74] The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [75]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [31,76,77], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [78][79][80][81][82].…”

Effects of photobiomodulation therapy on guided bone regeneration in defects filled by biphasic calcium phosphate associated with fibrin biopolymer

“…Allied to biphasic ceramics, the fibrin biopolymer (FBP) acting as a scaffold facilitated the insertion of the graft, and due to its three-dimensional structure, it promoted greater stability at the defect site [14,40,41]. Such findings are in line with studies that used FBP for the same purpose, obtaining favorable results in tissue regeneration [12,42].…”

Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review

“…In the study by Han et al (2014), bone formation was favored by the use of fibrin glue and MSCs associated with decalcified bone matrix. In contrast, in the study by Cassaro et al (2019), the use of scaffold containing only fibrin glue and MSCs exhibited higher bone formation than this scaffold associated with biphasic calcium phosphate. In other studies, fibrin glue loaded with MSCs showed a higher regenerative potential than the use of biphasic calcium phosphate with MSCs [39] or similar effect compared to autologous bone graft [40].…”

“…In contrast, residual fibrin glue still remained 2 months after implantation and no granulation tissue reaction was found [39]. In the study by Cassaro et al (2019), the presence of fibrin glue was not detected at the defect site after 30 days, suggesting that the reabsorption of the fibrin matrix occurred simultaneously with the formation of new bone. In many situations, the rate of degradation of fibrin glue can represent an advantage over bone substitutes of slow degradation.…”

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

“…The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [ 75 ]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [ 31 , 76 , 77 ], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [ 78 - 82 ].…”

“…The insertion of the xenogenic biomaterial, mainly with the association of another three-dimensional scaffold such as the fibrin biopolymer, creates a structured microenvironment, mainly in the central area of the defects, which prevents the invasion of soft tissues and may even reduce the need for guided bone regeneration procedures, with the addition of membranes to cover the defect [20,29,[71][72][73][74] The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [75]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [31,76,77], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [78][79][80][81][82].…”

Effects of photobiomodulation therapy on guided bone regeneration in defects filled by biphasic calcium phosphate associated with fibrin biopolymer

“…Allied to biphasic ceramics, the fibrin biopolymer (FBP) acting as a scaffold facilitated the insertion of the graft, and due to its three-dimensional structure, it promoted greater stability at the defect site [14,40,41]. Such findings are in line with studies that used FBP for the same purpose, obtaining favorable results in tissue regeneration [12,42].…”

Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review

“…In the study by Han et al (2014), bone formation was favored by the use of fibrin glue and MSCs associated with decalcified bone matrix. In contrast, in the study by Cassaro et al (2019), the use of scaffold containing only fibrin glue and MSCs exhibited higher bone formation than this scaffold associated with biphasic calcium phosphate. In other studies, fibrin glue loaded with MSCs showed a higher regenerative potential than the use of biphasic calcium phosphate with MSCs [39] or similar effect compared to autologous bone graft [40].…”

“…In contrast, residual fibrin glue still remained 2 months after implantation and no granulation tissue reaction was found [39]. In the study by Cassaro et al (2019), the presence of fibrin glue was not detected at the defect site after 30 days, suggesting that the reabsorption of the fibrin matrix occurred simultaneously with the formation of new bone. In many situations, the rate of degradation of fibrin glue can represent an advantage over bone substitutes of slow degradation.…”

A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy

“…The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [ 75 ]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [ 31 , 76 , 77 ], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [ 78 - 82 ].…”

“…The insertion of the xenogenic biomaterial, mainly with the association of another three-dimensional scaffold such as the fibrin biopolymer, creates a structured microenvironment, mainly in the central area of the defects, which prevents the invasion of soft tissues and may even reduce the need for guided bone regeneration procedures, with the addition of membranes to cover the defect [20,29,[71][72][73][74] The surgical cavities in which the fibrin biopolymer (XS and XS-PBM groups) were used showed intense angiogenesis as early as 14 days, as well as the occasional presence of granulation tissue and the permanence of vascular spaces at 42 days [75]. This biological response demonstrates that the biopolymer is biocompatible, in agreement with previous studies [31,76,77], because in addition to not having a foreign body reaction, it favored the insertion in the surgical bed, the deposition and proliferation of osteoblastic cells, functioning as a scaffold for bone regeneration [78][79][80][81][82].…”

Effects of photobiomodulation therapy on guided bone regeneration in defects filled by biphasic calcium phosphate associated with fibrin biopolymer

“…Allied to biphasic ceramics, the fibrin biopolymer (FBP) acting as a scaffold facilitated the insertion of the graft, and due to its three-dimensional structure, it promoted greater stability at the defect site [14,40,41]. Such findings are in line with studies that used FBP for the same purpose, obtaining favorable results in tissue regeneration [12,42].…”

Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review

“…In the study by Han et al (2014), bone formation was favored by the use of fibrin glue and MSCs associated with decalcified bone matrix. In contrast, in the study by Cassaro et al (2019), the use of scaffold containing only fibrin glue and MSCs exhibited higher bone formation than this scaffold associated with biphasic calcium phosphate. In other studies, fibrin glue loaded with MSCs showed a higher regenerative potential than the use of biphasic calcium phosphate with MSCs [39] or similar effect compared to autologous bone graft [40].…”

“…In contrast, residual fibrin glue still remained 2 months after implantation and no granulation tissue reaction was found [39]. In the study by Cassaro et al (2019), the presence of fibrin glue was not detected at the defect site after 30 days, suggesting that the reabsorption of the fibrin matrix occurred simultaneously with the formation of new bone. In many situations, the rate of degradation of fibrin glue can represent an advantage over bone substitutes of slow degradation.…”