Improving the degree of vascularization through the regulation of wound microenvironment is crucial for wound repair.Gene activated matrix(GAM)technology provides a new approach for skin regeneration.It is a local gen...Improving the degree of vascularization through the regulation of wound microenvironment is crucial for wound repair.Gene activated matrix(GAM)technology provides a new approach for skin regeneration.It is a local gene delivery system that can not only maintain a moist environment,but also increase the concentration of local active factors.For this purpose,we fabricated the mVEGF165/TGF-β1 gene-loaded N-carboxymethyl chitosan/sodium alginate hydrogel and studied its effect on promoting deep second degree burn wound repair.The average diameter of the hydrogel pores was 100μm and the porosity was calculated as 50.9%.SEM and CLSM images showed that the hydrogel was suitable for cell adhesion and growth.The NS-GAM could maintain continuous expression for at least 9 days in vitro,showing long-term gene release and expression effect.Deep second-degree burn wound model was made on the backs of Wistar rats to evaluate the healing effect.The wounds were healed by day 22 in NS-GAM group with the prolonged high expression of VEGF and TGF-β1 protein.A high degree of neovascularization and high expression level of CD34 were observed in NS-GAM group in 21 days.The histological results showed that NS-GAM had good tissue safety and could effectively promote epithelialization and collagen regeneration.These results indicated that the NS-GAM could be applied as a promising local gene delivery system for the repair of deep second-degree burn wounds.展开更多
Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, prop...Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 （hBMP2） gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty ＋ hBMP2 plasmid was injected into the right thigh muscle pouches of the mice （experiment side）. The nanobone putty ＋ blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 （control side 1） or group 2 （control side 2）, respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups： Group A, nanobone putty ＋ hBMP2 plasmid; Group B, putty ＋ blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. Conclusions The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capabilitv than that of nanobone putty only.展开更多
Currently, the gold standard for aesthetic and functional reconstruction of critical mandibular defects is an autologous fibular flap;however, this carries risk of donor site morbidity, and is not a promising option i...Currently, the gold standard for aesthetic and functional reconstruction of critical mandibular defects is an autologous fibular flap;however, this carries risk of donor site morbidity, and is not a promising option in patients with depleted donor sites due to previous surgeries. Tissue engineering presents a potential solution in the design of a biomimetic scaffold that must be osteoconductive, osteoinductive, and support osseointegration. These osteogenesis-inducing scaffolds are most successful when they mimic and interact with the surrounding native macro- and micro-environment of the mandible. This is accomplished via the regeneration triad: (1) a biomimetic, bioactive osteointegrative scaffold, most likely a resorbable composite of collagen or a synthetic polymer with collagen-like properties combined with beta-tri calcium phosphate that is 3D printed according to defect morphology;(2) growth factor, most frequently bone morphogenic protein 2 (BMP-2);and (3) stem cells, most commonly bone marrow mesenchymal stem cells. Novel techniques for scaffold modification include the use of nano-hydroxyapatite, or combining a vector with a biomaterial to create a gene activated matrix that produces proteins of interest (typically BMP-2) to support osteogenesis. Here, we review the current literature in tissue engineering in order to discuss the success of varying use and combinations of scaffolding materials (i.e., ceramics, biological polymers, and synthetic polymers) with stem cells and growth factors, and will examine their success in vitro and in vivo to induce and guide osteogenesis in mandibular defects.展开更多
基金National Natural Science Foundation of China(No.51773188)Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016)The National Key Research and Development Program of China(No.2018YFC1105602,2018YFD0900601).
文摘Improving the degree of vascularization through the regulation of wound microenvironment is crucial for wound repair.Gene activated matrix(GAM)technology provides a new approach for skin regeneration.It is a local gene delivery system that can not only maintain a moist environment,but also increase the concentration of local active factors.For this purpose,we fabricated the mVEGF165/TGF-β1 gene-loaded N-carboxymethyl chitosan/sodium alginate hydrogel and studied its effect on promoting deep second degree burn wound repair.The average diameter of the hydrogel pores was 100μm and the porosity was calculated as 50.9%.SEM and CLSM images showed that the hydrogel was suitable for cell adhesion and growth.The NS-GAM could maintain continuous expression for at least 9 days in vitro,showing long-term gene release and expression effect.Deep second-degree burn wound model was made on the backs of Wistar rats to evaluate the healing effect.The wounds were healed by day 22 in NS-GAM group with the prolonged high expression of VEGF and TGF-β1 protein.A high degree of neovascularization and high expression level of CD34 were observed in NS-GAM group in 21 days.The histological results showed that NS-GAM had good tissue safety and could effectively promote epithelialization and collagen regeneration.These results indicated that the NS-GAM could be applied as a promising local gene delivery system for the repair of deep second-degree burn wounds.
文摘Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 （hBMP2） gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty ＋ hBMP2 plasmid was injected into the right thigh muscle pouches of the mice （experiment side）. The nanobone putty ＋ blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 （control side 1） or group 2 （control side 2）, respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups： Group A, nanobone putty ＋ hBMP2 plasmid; Group B, putty ＋ blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. Conclusions The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capabilitv than that of nanobone putty only.
文摘Currently, the gold standard for aesthetic and functional reconstruction of critical mandibular defects is an autologous fibular flap;however, this carries risk of donor site morbidity, and is not a promising option in patients with depleted donor sites due to previous surgeries. Tissue engineering presents a potential solution in the design of a biomimetic scaffold that must be osteoconductive, osteoinductive, and support osseointegration. These osteogenesis-inducing scaffolds are most successful when they mimic and interact with the surrounding native macro- and micro-environment of the mandible. This is accomplished via the regeneration triad: (1) a biomimetic, bioactive osteointegrative scaffold, most likely a resorbable composite of collagen or a synthetic polymer with collagen-like properties combined with beta-tri calcium phosphate that is 3D printed according to defect morphology;(2) growth factor, most frequently bone morphogenic protein 2 (BMP-2);and (3) stem cells, most commonly bone marrow mesenchymal stem cells. Novel techniques for scaffold modification include the use of nano-hydroxyapatite, or combining a vector with a biomaterial to create a gene activated matrix that produces proteins of interest (typically BMP-2) to support osteogenesis. Here, we review the current literature in tissue engineering in order to discuss the success of varying use and combinations of scaffolding materials (i.e., ceramics, biological polymers, and synthetic polymers) with stem cells and growth factors, and will examine their success in vitro and in vivo to induce and guide osteogenesis in mandibular defects.
