Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the denta...Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.展开更多
Sclerostin is a Wnt signalling antagonist that controls bone metabolism. Sclerostin is expressed by osteocytes and cementocytes; however, its role in the formation of dental structures remains unclear. Here, we analys...Sclerostin is a Wnt signalling antagonist that controls bone metabolism. Sclerostin is expressed by osteocytes and cementocytes; however, its role in the formation of dental structures remains unclear. Here, we analysed the mandibles of sclerostin knockout mice to determine the influence of sclerostin on dental structures and dimensions using histomorphometry and micro-computed tomography (μCT) imaging, μCT and histomorphometric analyses were performed on the first lower molar and its surrounding structures in mice lacking a functional sclerostin gene and in wild-type controls, pCT on six animals in each group revealed that the dimension of the basal bone as well as the coronal and apical part of alveolar part increased in the sclerostin knockout mice. No significant differences were observed for the tooth and pulp chamber volume. Descriptive histomorphometric analyses of four wild-type and three sclerostin knockout mice demonstrated an increased width of the cementum and a concomitant moderate decrease in the periodontal space width. Taken together, these results suggest that the lack of sclerostin mainly alters the bone and cementum phenotypes rather than producing abnormalities in tooth structures such as dentin.展开更多
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
基金Supported by Austrian Science Fund,No.Project 29440(to Andrukhov O)
文摘Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.
基金The Department of Oral Surgery,Head Professor G Watzek,Bernhard Gottlieb Dental School,and the Medical University of Vienna financially supported the analysis
文摘Sclerostin is a Wnt signalling antagonist that controls bone metabolism. Sclerostin is expressed by osteocytes and cementocytes; however, its role in the formation of dental structures remains unclear. Here, we analysed the mandibles of sclerostin knockout mice to determine the influence of sclerostin on dental structures and dimensions using histomorphometry and micro-computed tomography (μCT) imaging, μCT and histomorphometric analyses were performed on the first lower molar and its surrounding structures in mice lacking a functional sclerostin gene and in wild-type controls, pCT on six animals in each group revealed that the dimension of the basal bone as well as the coronal and apical part of alveolar part increased in the sclerostin knockout mice. No significant differences were observed for the tooth and pulp chamber volume. Descriptive histomorphometric analyses of four wild-type and three sclerostin knockout mice demonstrated an increased width of the cementum and a concomitant moderate decrease in the periodontal space width. Taken together, these results suggest that the lack of sclerostin mainly alters the bone and cementum phenotypes rather than producing abnormalities in tooth structures such as dentin.