Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5 µg) or saline at the time of surgery. Three weeks postsurgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by two fold compared with saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice.

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

The effects of ethyl-2-cyanoacrylate and butyl-2-cyanoacrylate in the process of bone healing in rats. A controlled experimental study / Efeitos do etil-2-cianoacrilato e do butil-2-cianoacrilato no processo de consolidação óssea em ratos. Estudo experimental controlado

ABSTRACT Objective: Synthetic adhesives are used by various medical specialties, especially in surgery; however, studies reporting their use in orthopedic practice are scarce. The aim of this study was to compare the results in using ethyl-2-cyanoacrylate or butyl-2-cyanoacrylate in the treatment of fractures in rats. Methods: This was an experimental prospective controlled study in 90 rats, with humerus, femur, and tibia fractures, treated with ethyl-2-cyanoacrylate (SB group; n = 45) or butyl-2-cyanoacrylate (HA group; n = 45). Biomechanical and histomorphometric analyses were performed at three different moments (60, 120, and 180 days); besides a clinical study performed weekly by measurement of the animals body mass. Results: No differences were observed regarding body mass (p = 0.07). In both groups, there were no significant differences regarding maximum load (p = 0.6), yield point strength (p = 0.6), and stiffness coefficient (p = 0.4) of the femurs. The same was observed in tibias for maximum load (p = 0.4), yield point strength (p = 0.7), and stiffness coefficient (p = 0.6). The humerus from both groups had similar bone callus area (p = 0.66). In both groups, there were no statistical differences related to inflammatory cells (p = 0.4), osteoblasts (p = 0.2), and osteoclasts (p = 0.2). Conclusion: Ethyl-2-cyanoacrylate was more effective than butyl-2-cyanoacrylate in the treatment of fractures in rats.

RESUMO Objetivo: Os adesivos sintéticos são usados em várias especialidades médicas cirúrgicas, contudo, os estudos que relatam seu uso na prática ortopédica são escassos. O objetivo deste trabalho foi comparar os resultados do uso do etil-2-cianoacrilato e do butil-2-cianoacrilato no tratamento de fraturas em ratos. Métodos: Foi realizado um estudo experimental, prospectivo e controlado em 90 ratos com fraturas de úmero, fêmur e tíbia, tratados com etil-2-cianoacrilato (grupo SB; n = 45) ou butil-2-cianoacrilato (grupo HA; n = 45). Foram realizadas análises biomecânicas e histomorfométricas em três momentos (60, 120 e 180 dias), além do estudo clínico pela aferição semanal da massa corporal dos animais. Resultados: Não foram observadas diferenças relacionadas à massa corporal dos animais (p = 0,07). Os fêmures de ambos os grupos não apresentaram diferença com relação à carga máxima (p = 0,6), limite de elasticidade (p = 0,6) e coeficiente de rigidez (p = 0,4). Analisando-se as tíbias, o mesmo foi observado com relação à carga máxima (p = 0,4), ao limite de elasticidade (p = 0,7) e ao coeficiente de rigidez (p = 0,6). Os úmeros de ambos os grupos apresentaram a mesma área de calo ósseo formado (p = 0,66). Em ambos os grupos, não houve diferença estatística relacionada ao número de osteoblastos (p = 0,2), osteoclastos (p = 0,2) e células inflamatórias (p = 0,4). Conclusão: O etil-2-cianoacrilato foi mais eficaz do que o butil-2-cianoacrilato no tratamento de fraturas em ratos.

The effects of ethyl-2-cyanoacrylate and butyl-2-cyanoacrylate in the process of bone healing in rats. A controlled experimental study.

OBJECTIVE: Synthetic adhesives are used by various medical specialties, especially in surgery; however, studies reporting their use in orthopedic practice are scarce. The aim of this study was to compare the results in using ethyl-2-cyanoacrylate or butyl-2-cyanoacrylate in the treatment of fractures in rats. METHODS: This was an experimental prospective controlled study in 90 rats, with humerus, femur, and tibia fractures, treated with ethyl-2-cyanoacrylate (SB group; n = 45) or butyl-2-cyanoacrylate (HA group; n = 45). Biomechanical and histomorphometric analyses were performed at three different moments (60, 120, and 180 days); besides a clinical study performed weekly by measurement of the animals body mass. RESULTS: No differences were observed regarding body mass (p = 0.07). In both groups, there were no significant differences regarding maximum load (p = 0.6), yield point strength (p = 0.6), and stiffness coefficient (p = 0.4) of the femurs. The same was observed in tibias for maximum load (p = 0.4), yield point strength (p = 0.7), and stiffness coefficient (p = 0.6). The humerus from both groups had similar bone callus area (p = 0.66). In both groups, there were no statistical differences related to inflammatory cells (p = 0.4), osteoblasts (p = 0.2), and osteoclasts (p = 0.2). CONCLUSION: Ethyl-2-cyanoacrylate was more effective than butyl-2-cyanoacrylate in the treatment of fractures in rats.

OBJETIVO: Os adesivos sintéticos são usados em várias especialidades médicas cirúrgicas, contudo, os estudos que relatam seu uso na prática ortopédica são escassos. O objetivo deste trabalho foi comparar os resultados do uso do etil-2-cianoacrilato e do butil-2-cianoacrilato no tratamento de fraturas em ratos. MÉTODOS: Foi realizado um estudo experimental, prospectivo e controlado em 90 ratos com fraturas de úmero, fêmur e tíbia, tratados com etil-2-cianoacrilato (grupo SB; n = 45) ou butil-2-cianoacrilato (grupo HA; n = 45). Foram realizadas análises biomecânicas e histomorfométricas em três momentos (60, 120 e 180 dias), além do estudo clínico pela aferição semanal da massa corporal dos animais. RESULTADOS: Não foram observadas diferenças relacionadas à massa corporal dos animais (p = 0,07). Os fêmures de ambos os grupos não apresentaram diferença com relação à carga máxima (p = 0,6), limite de elasticidade (p = 0,6) e coeficiente de rigidez (p = 0,4). Analisando-se as tíbias, o mesmo foi observado com relação à carga máxima (p = 0,4), ao limite de elasticidade (p = 0,7) e ao coeficiente de rigidez (p = 0,6). Os úmeros de ambos os grupos apresentaram a mesma área de calo ósseo formado (p = 0,66). Em ambos os grupos, não houve diferença estatística relacionada ao número de osteoblastos (p = 0,2), osteoclastos (p = 0,2) e células inflamatórias (p = 0,4). CONCLUSÃO: O etil-2-cianoacrilato foi mais eficaz do que o butil-2-cianoacrilato no tratamento de fraturas em ratos.