journal of the mechanical behavior of biomedical materials 104 (2020) 103662 Available online 29 January 2020 1751-6161/© 2020 Elsevier Ltd. All rights reserved. Effects of fbrin sealant and bone fragments on defect regeneration performed on rat tibiae: An experimental study Carla Teresa Barbosa de Oliveira a, * , Bruna Carlos Leonel a , Ana Clara de Oliveira a , Marcela de Brito Paiva a , Junia Ramos b , Benedito Barraviera c , Rui Seabra Ferreira Junior c , Ant^ onio Carlos Shimano a a Bioengineering Laboratory of Medical School of Ribeir~ ao Preto, S~ ao Paulo University, Avenida do Caf� e S/N, Monte Alegre, Ribeir~ ao Preto, CEP: 14040-904, S~ ao Paulo, Brazil b Dental School of Ribeir~ ao Preto, S~ ao Paulo University, Avenida do Caf� e S/N, Monte Alegre, Ribeir~ ao Preto, CEP: 14040-904, S~ ao Paulo, Brazil c Center for the Study of Venoms and Venomous Animals, S~ ao Paulo State Universtiy, Rua Jos� e Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu, CEP: 18610-307, S~ ao Paulo, Brazil A R T I C L E INFO Keywords: Fibrin tissue adhesive Bone regeneration Autologous transplantation Tibia Rats ABSTRACT Fibrin sealant (FS) is a biomaterial that exhibits hemostatic and repairing properties. It has been successfully used as scaffolds and adhesives to improve repair and regeneration of tissues. The objective of this study was to evaluate the effect of FS in the regeneration process of bone defects in male rat tibias through macroscopic, microscopic and mechanical analysis. A bone defect of 2.9 mm was performed on the medial face of the proximal third of the tibia of 40 rats and implanted FS and autologous bone graft (AG). The animals were divided into four groups: animals with bone defect without any treatment (CON), animals treated with fbrin sealant (TFS), ani- mals treated with autologous graft (TAG) and animals treated with fbrin sealant and autologous graft (FSAG). The animals were euthanized 42 days after surgery. Macroscopic analysis showed no difference between the groups (p > 0.05) in relation to tibial weight, but a statistically signifcant difference (p ¼ 0.005) was observed for their length. Micro-computed tomography (micro-CT) revealed tendentious values regarding bone micro- architecture and FS. Bone mineral densitometry (BMD) showed signifcance between the FSAG (p ¼ 0.009) and TFS (p ¼ 0.007) groups. The bone mineral content (BMC) presented a signifcant difference between all groups (p ¼ 0.020). Maximum strength showed a signifcant difference between the FSAG group (p ¼ 0.007) and the others. The results obtained in relation to the relative stiffness also present a signifcant difference (p ¼ 0.023). Newly formed bone showed signifcant differences between groups (p ¼ 0.035). We conclude that bone defect regeneration was directly infuenced by the use of FS and AG. 1. Introduction The treatment of comminuted fractures requires the use of appro- priate surgical techniques, such as osteosynthesis using plates, screws and/or pins. However, these materials are generally available for bone fragments up to 1 cm (Wistlich et al., 2017). Thus, fragments that are left over or those that are very small are left at the site of the bone defect or are simply removed (Song et al., 2014). The conservative treatment for this type of fracture also presents diffculties such as reduction and immobilization with cast or splint (Leung et al., 1990). Therefore, alternative fxation techniques such as bone adhesives may be used (Wistlich et al., 2017). Shah and Meislin (2013) report that clinical use of bone glue by orthopedic surgeons is increasingly common, as in avulsion fractures and bone fragments with minimal soft tissue exposure and especially in very comminuted fractures with very small fragments. Fibrin sealant (FS) and its adhesive properties have been studied in different tissues (Machado et al., 2015). FS is a biomaterial that exhibits hemostatic and repairing properties. It has been successfully used as scaffolds and adhesives to improve tissue repair and regeneration * Corresponding author. E-mail addresses: carla.teresa@hotmail.com (C.T.B. de Oliveira), brunaleonel@usp.br (B.C. Leonel), anaclara.19@usp.br (A.C. de Oliveira), marcelapaiva@usp.br (M. de Brito Paiva), juniaramos@usp.br (J. Ramos), bbviera@jvat.org.br (B. Barraviera), rseabra@cevap.unesp.br (R.S. Ferreira Junior), ashimano@fmrp.usp.br (A.C. Shimano). Contents lists available at ScienceDirect Journal of the Mechanical Behavior of Biomedical Materials journal homepage: http://www.elsevier.com/locate/jmbbm https://doi.org/10.1016/j.jmbbm.2020.103662 Received 3 June 2019; Received in revised form 24 January 2020; Accepted 27 January 2020