Epidermal Growth Factor Stimulates Rabbit Achilles Tendon Histologically and Biomechanically Healing

Abstract

Background. Epidermal Growth Factor (EGF) stimulates epidermis cell growth, proliferation and differentiation in skin regeneration. The aim of this study was to pre-clinically investigation of the role of EGF in tendon healing. Methods. One cm defects were created at the right Achilles tendons of 30 New Zealand White rabbits. Ten rabbits were allocated to one of three groups: Group-1-(Sham) tendon defect with a gap that was splinted with a non-absorbable suture; Group-2-(EGF +) tendon defect with a gap that was splinted with a non-absorbable suture and a 25 µg/kg EGF injection into the defect; Group-3-(Scaffold + EGF) tendon defect was grafted with a biodegradable, porous Polycaprolactone (PCL) scaffold loaded with 25 µg/kg EGF and stabilized with a non-absorbable suture. Animals were sacrificed at 8 weeks post-surgery and Achilles tendon repair and healing status was investigated using histopathologic and biomechanical analysis methods. Results. Group-2-(EGF +) had greater adipocyte development (moderate) than Group-1-(Sham) and Group-3-(Scaffold + EGF). Group-2-(EGF +) and Group-3-(Scaffold + EGF) had greater peripheral nerve development (weak) than Group-1-(Sham). Group-2-(EGF +) had greater vascularization (moderate) than Group-1-(Sham) and Group-3-(Scaffold + EGF). Group-2-(EGF +) had greater collagen Type-III development (moderate) than Group-1-(Sham) and Group-3-(Scaffold + EGF). Group-3-(Scaffold + EGF) had greater collagen Type-I development (moderate) than Group-1-(Sham) and Group-2-(EGF +). Groups did not display statistically significant differences for load to failure or elongation at failure. Group-2-(EGF +) and Group-3-(Scaffold + EGF) displayed less stiffness that the control (healthy contralateral Achilles tendon) (p < 0.05), however, experimental groups did not differ (p > 0.05). Conclusions. The application of EGF and scaffold displayed superior histological tendon healing evidence, but there was no significant difference in terms of biomechanics.

Investigação do efeito do fator de crescimento epidérmico recombinante humano na cicatrização do manguito rotador: Um modelo experimental

“…However, they did not detect any biomechanical strength differences between EGF-treated and non-treated groups. 24 Similarly, we found increased vascularity, greater collagen deposition, and higher fibroblastic activity in EGF-treated rabbits with RCT. However, we were unable to conduct biomechanical strength tests because the bone tendon junction is rather weak in the animal rotator cuff.…”

“… 23 Basal et al 11 reported that EGF improves bone formation and microcirculation by provoking neoangiogenesis in early-stage osteonecrosis of the femoral head. Kocyigit et al 24 investigated the effects of EGF treatment in a rat model of Achilles tendon healing and found more extensive vascularization, greater pericyte concentrations adjacent to vessel endothelial cells, and higher adipocyte concentrations in EGF-treated rats than in a normally healed group. However, they did not detect any biomechanical strength differences between EGF-treated and non-treated groups.…”

“… 23 Basal et al 11 relataram que o EGF melhora a formação óssea e a microcirculação ao provocar neoangiogênese no início da osteonecrose da cabeça do fêmur. Kocyigit et al 24 investigaram os efeitos do tratamento com EGF em um modelo de cicatrização do tendão calcâneo em ratos e observaram maior vascularidade, maiores concentrações de pericitos adjacentes às células endoteliais dos vasos e maiores concentrações de adipócitos em ratos tratados com EGF em comparação ao grupo de cicatrização normal. No entanto, não detectaram diferenças de força biomecânica entre os grupos tratados ou não com EGF.…”

“…No entanto, não detectaram diferenças de força biomecânica entre os grupos tratados ou não com EGF. 24 Da mesma forma, observamos aumento da vascularização, maior deposição de colágeno e maior atividade fibroblástica em coelhos com RMR tratados com EGF. Porém, não pudemos realizar testes de resistência biomecânica porque a junção tendão-ósseo é muito baixa no manguito rotador do animal.…”

Treatment with Conditioned Medium from Tenocytes Primary Cell Cultures Accelerates Histological and Functional Recovery of Achilles Tendon in Tenotomized Mice

“…Tibia region of the right paw was tricotomized and a longitudinal skin incision was performed to access Achilles. After that, the right tendon was transected in axial fashion at 0.5 cm from calcaneal insertion followed by Kessler suture (25,26). Afterwards, the tendon and skin were sutured with non-absorbable monofilament polyamide thread number 4.0 from TechFio ® and subjected to local asepsis.…”