Transected Tendon Treated with a New Fibrin Sealant Alone or Associated with Adipose-Derived Stem Cells
Katleen Frauz,
Luis Felipe R. Teodoro,
Giane Daniela Carneiro,
Fernanda Cristina da Veiga,
Danilo Lopes Ferrucci,
André Luis Bombeiro,
Priscyla Waleska Simões,
Lúcia Elvira Álvares,
Alexandre Leite R. de Oliveira,
Cristina Pontes Vicente,
Rui Seabra Ferreira,
Benedito Barraviera,
Maria Esméria C. do Amaral,
Marcelo Augusto M. Esquisatto,
Benedicto de Campos Vidal,
Edson Rosa Pimentel,
Andrea Aparecida de Aro
Affiliations
Katleen Frauz
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Luis Felipe R. Teodoro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Giane Daniela Carneiro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Fernanda Cristina da Veiga
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Danilo Lopes Ferrucci
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
André Luis Bombeiro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Priscyla Waleska Simões
Engineering, Modeling and Applied Social Sciences Center (CECS), Biomedical Engineering Graduate Program (PPGEBM), Universidade Federal do ABC (UFABC), Alameda da Universidade s/n, 09606-045 São Bernardo do Campo, SP, Brazil
Lúcia Elvira Álvares
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Alexandre Leite R. de Oliveira
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Cristina Pontes Vicente
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Rui Seabra Ferreira
Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP – Universidade Estadual Paulista), Botucatu, SP, St. José Barbosa de Barros, 1780, Fazenda Experimental Lageado, 18610-307 Botucatu, SP, Brazil
Benedito Barraviera
Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP – Universidade Estadual Paulista), Botucatu, SP, St. José Barbosa de Barros, 1780, Fazenda Experimental Lageado, 18610-307 Botucatu, SP, Brazil
Maria Esméria C. do Amaral
Biomedical Sciences Graduate Program, Herminio Ometto University Center-UNIARARAS, Av. Dr. Maximiliano Baruto, 500, Jd. Universitário, 13607-339 Araras, SP, Brazil
Marcelo Augusto M. Esquisatto
Biomedical Sciences Graduate Program, Herminio Ometto University Center-UNIARARAS, Av. Dr. Maximiliano Baruto, 500, Jd. Universitário, 13607-339 Araras, SP, Brazil
Benedicto de Campos Vidal
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Edson Rosa Pimentel
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Andrea Aparecida de Aro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas–UNICAMP, Charles Darwin, s/n, CP 6109, 13083-970 Campinas, SP, Brazil
Tissue engineering and cell-based therapy combine techniques that create biocompatible materials for cell survival, which can improve tendon repair. This study seeks to use a new fibrin sealant (FS) derived from the venom of Crotalus durissus terrificus, a biodegradable three-dimensional scaffolding produced from animal components only, associated with adipose-derived stem cells (ASC) for application in tendons injuries, considered a common and serious orthopedic problem. Lewis rats had tendons distributed in five groups: normal (N), transected (T), transected and FS (FS) or ASC (ASC) or with FS and ASC (FS + ASC). The in vivo imaging showed higher quantification of transplanted PKH26-labeled ASC in tendons of FS + ASC compared to ASC on the 14th day after transection. A small number of Iba1 labeled macrophages carrying PKH26 signal, probably due to phagocytosis of dead ASC, were observed in tendons of transected groups. ASC up-regulated the Tenomodulin gene expression in the transection region when compared to N, T and FS groups and the expression of TIMP-2 and Scleraxis genes in relation to the N group. FS group presented a greater organization of collagen fibers, followed by FS + ASC and ASC in comparison to N. Tendons from ASC group presented higher hydroxyproline concentration in relation to N and the transected tendons of T, FS and FS + ASC had a higher amount of collagen I and tenomodulin in comparison to N group. Although no marked differences were observed in the other biomechanical parameters, T group had higher value of maximum load compared to the groups ASC and FS + ASC. In conclusion, the FS kept constant the number of transplanted ASC in the transected region until the 14th day after injury. Our data suggest this FS to be a good scaffold for treatment during tendon repair because it was the most effective one regarding tendon organization recovering, followed by the FS treatment associated with ASC and finally by the transplanted ASC on the 21st day. Further investigations in long-term time points of the tendon repair are needed to analyze if the higher tissue organization found with the FS scaffold will improve the biomechanics of the tendons.
