Transected Tendon Treated with a New Fibrin Sealant Alone or Associated with Adipose-Derived Stem Cells

Abstract

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.

Microcurrent and adipose‐derived stem cells modulate genes expression involved in the structural recovery of transected tendon of rats

“…With relation to the ASC therapy, it was possible to observe the cells migration to TR of tendons, an important effect for tendon healing due the paracrine secretion of ASC. A previous study by our group showed that the ability of ASC to remain in the TR of rat Achilles tendon was on the average of 6% from the 1st to 2nd day after application of the cells 3 . Regarding the collagen, after the application of ASC in the present study, no difference was demonstrated in both expression and amount of collagen types I and III in comparison to the control, neither in the total collagen concentration.…”

“…A transverse partial transection (approximately 2/3 of the extent of the injury in-depth) was performed in the proximal tendon region located at a distance of 4 mm from its insertion in the calcaneus bone. 3,5,24,37 Approximately 4.5 × 10 5 ASC (6/7P) were resuspended in 30 μL of DMPBS Flush and transplanted in the TR of tendons in the C and MC groups, using a pipette. In tendons of T and M groups, only 30 μL of DMPBS Flush was applied.…”

“…30,31 In recent years, several studies have been carried out in rats, horses, and sheep among other animal models, using ASC with the objective of making tendon repair more effective. [3][4][5][24][25][26][27][28]32,33 However, there is still no standardization regarding the number of ASC to be applied in the injured tendon region, considering that the number of cells incorporated in the tissue is low. It is also important to observe that the molecular mechanisms involved during tendon recovery after ASC application are still poorly understood.…”

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

“…When used in combination with fibrin sealant or hydrogels, ASC treatment has been reported improved tendon healing with increased expression of Col1, Scx, and Tenomodulin in the damaged tendon tissue. In vivo survival of ASCs injected with scaffolds (fibrin sealant or hydrogel) into the defect region was confirmed at day 14 [127] and day 31, post injury [202]. While these studies effectively demonstrate that there are several different approaches for utilizing exogenous cell treatments (with/without bioactive scaffolds or growth factors) to stimulate tendon and ligament repair [119,120,127,183,184,202], further comprehensive studies are needed to assess the safety and efficacy of these approaches to take the research from bench-to-bedside.…”

Fibrin Biopolymer Incorporated with Antimicrobial Agents: A Proposal for Coating Denture Bases

“…More recently, a new heterologous fibrin sealant composed of fibrinogen-rich cryoprecipitate, extracted from Bubalus bubalis buffalo blood, and a thrombin-like enzyme, purified from the venom of Crotalus durissus terrificus, has been considered as a promising material in medicine and dentistry [ 32 , 33 , 34 , 35 , 36 ]. This biopolymer has biocompatibility (nontoxic), low-cost to produce in addition to hemostatic, sealant, adhesive, scaffold, and drug delivery properties [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. In the presence of calcium, the thrombin-like enzyme acts on fibrinogen molecules, turning them into fibrin monomers, resulting in a stable clot [ 33 , 34 , 35 ].…”