Fibrin biopolymer as scaffold candidate to treat bone defects in rats

 

Claudia Vilalva Cassaro¹, Luis Antonio Justulin Jr.³, Patrícia Rodrigues de Lima^1  2 , Marjorie de Assis Golim⁴, Natália Perussi Biscola¹, Mateus Vidigal de Castro⁵, Alexandre Leite Rodrigues de Oliveirazz⁵, Danuta Pulz Doiche⁶, Elenize Jamas Pereira^1  2, Rui Seabra Ferreira Jr.^1  2, Benedito Barraviera^1  2 

 

1 Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, SP, Brazil.

2 Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, SP, Brazil.

3 Extracellular Matrix Laboratory, Botucatu Biosciences Institute (IBB), São Paulo State University (UNESP), Botucatu, SP, Brazil.

4 Flow Cytometry Laboratory, Blood Center, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, SP, Brazil.

5 Department of Structural and Functional Biology, Biosciences Institute (IB), University of Campinas (UNICAMP), Campinas, SP, Brazil.

6 Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Husbandry, São Paulo State University (UNESP), Botucatu, SP, Brazil.

 

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.

 

Keywords: Bone regeneration; Biomaterials; Fibrin sealant; Fibrin biopolymer; Biphasic calcium phosphate; Mesenchymal stem cells

 

Received: May 04, 2019.

Accepted: October 01, 2019.

 

Correspondence: claudia.v.cassaro@gmail.com

 

Competing interests

Benedito Barraviera, Rui Seabra Ferreira Jr. and Claudia Vilalva Cassaro, authors of this article, are respectively editor-in-chief, associate and junior editors of Journal of Venomous Animals and Toxins including Tropical Diseases. They did not get involved in the peer review process of this manuscript.

 

Authors' contributions

CVC performed the surgical procedures, euthanasia, acquisition and material processing, analysis and interpretation of data. LAJJ helped with histological preparation, processing and analysis. PRL assisted in stem cell isolation and expansion and surgical procedures. MAG analyzed data generated by flow cytometry of cultivated mesenchymal stem cells. NPB, MVC and ALRO contributed to standardization of scanning electron microscopy procedure. DPD performed micro-CT scan and image processing on specific softwares. EJP, RSFJ, and BB contributed to the design of the study, analysis and interpretation of data. All authors revised the manuscript to important intellectual content. All of the authors have read and approved the manuscript.