Antimicrobial delivery has been advocated for guided tissue regeneration (GTR) or guided bone regeneration (GBR) therapies involving patients with aggressive or unresolved periodontitis/peri-implantitis. Electrospun c...Antimicrobial delivery has been advocated for guided tissue regeneration (GTR) or guided bone regeneration (GBR) therapies involving patients with aggressive or unresolved periodontitis/peri-implantitis. Electrospun chitosan membranes demonstrate several advantages over traditional GTR barrier membranes because they stimulate healing, mimic the topology of the extracellular matrix, and allow for diffusion of nutrients and wastes into/out of the graft site, and were shown to stimulate bone formation in a rabbit calvarial criticalsize defect model. Previously, we have shown improvements in mechanical properties and degradation kinetics by crosslinking electrospun membranes with 5 mM or 10 mM genipin. We have also demonstrated the ability of elecrospun chitosan membranes to inhibit lippopolysaccharide (LPS)-induced monocyte activation. In this study, minocycline was incorporated into the chitosan membrane by passive absorption at 5 or 10 mg/mL. The minocycline-loaded membranes and control membranes (carrier only) were tested against Porphyromonas gingivalis (P. gingivalis) by repeated zone of inhibition (ZOI) measurements. Testing showed that uncrosslinked and genipin-crosslinked membranes have similar capacity to absorb aqueous solutions (swelling ratio 1.7 - 2.2). Minocycline loading resulted in bacterial inhibition for up to 8 days from crosslinked membranes (with 11 mm initial ZOI) whereas uncrosslinked membranes loaded with minocycline only inhibited bacteria for 4 days (with 8 mm initial ZOI). These in vitro results suggest that genipin-crosslinked electrospun chitosan membranes loaded with minocycline may be able to reduce early bacterial contamination of GTR graft sites.展开更多
Chitosan nanofiber membranes have been known to have a high degree of biocompatibility and support new bone formation with controllable biodegradation. The surface area of these membranes may allow them to serve as lo...Chitosan nanofiber membranes have been known to have a high degree of biocompatibility and support new bone formation with controllable biodegradation. The surface area of these membranes may allow them to serve as local delivery carriers for different biologic mediators. Simvastatin, a drug commonly used for lowering cholesterol, has demonstrated promising bone regenerative capability. The aim of this study was to evaluate simvastatin loaded chitosan nanofiber membranes for guided bone regeneration (GBR) applications and their ability to enhance bone formation in rat calvarial defects. Nanofibrous chitosan membranes with random fiber orientation were fabricated by electrospinning technique and loaded with 0.25 mg of simvastatin under sterile conditions. One membrane was implanted subperiosteally to cover an 8 mm diameter critical size calvarial defect. Two groups: 1) Control: non-loaded chitosan membranes;2) Experimental: chitosan membranes loaded with 0.25 mg of simvastatin were evaluated histologically and via micro-computed tomography (micro-CT) for bone formation at 4 and 8 weeks time points (n = 5/group per time point). Both groups exhibited good biocompatibility with only mild or moderate inflammatory response during the healing process. Histologic and micro-CT evaluations confirmed bone formation in calvarial defects as early as 4 weeks using control and experimental membranes. In addition, newly-formed bony bridges consolidating calvarial defects histologically along with partial radiographic defect coverage were observed at 8 weeks in both groups. Although control and experimental groups demonstrated no significant statistical differences in results of bone formation, biodegradable chitosan nanofiber membranes loaded with simvastatin showed a promising regenerative potential as a barrier material for guided bone regeneration applications.展开更多
Treating bone defects is a critical challenge in regenerative medicine.Carbon nanomaterials,with their unique physicochemical properties,offer significant potential for enhancing bone regeneration.In this study,we dev...Treating bone defects is a critical challenge in regenerative medicine.Carbon nanomaterials,with their unique physicochemical properties,offer significant potential for enhancing bone regeneration.In this study,we developed tartaric acid(TA)-based carbon dots(CDs)by synthesizing TA with branched polyethyleneimine(bPEI).These TA-bPEI CDs were systematically evaluated to determine their effects on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells(BMSCs)and their capacity to repair calvarial defects in an in vivo model.Characterization of TA-bPEI CDs revealed a size of approximately 10nm and a positive surface charge.The CDs exhibited fluorescence emission peaks between 464 and 506 nm under excitation wavelengths of 340–440nm.Cytotoxicity assays demonstrated that TA-bPEI CDs maintained BMSC viability at concentrations up to 250μg/ml.However,at concentrations of 500μg/ml and above,apoptosis was induced.Treatment with TA-bPEI significantly enhanced osteogenic differentiation in vitro,as evidenced by increased expression of osteogenic-specific proteins such as Runx2,ALP,OCN and OPN.In vivo,the application of TA-bPEI CDs in a mouse calvarial defect model promoted robust new bone formation,reduced defect gaps,and improved bone morphometric parameters,including bone volume fraction and trabecular thickness.These results suggest that TA-bPEI CDs enhance osteogenesis by directly stimulating osteogenic differentiation and upregulating osteogenesis-specific genes.This study demonstrates the high potential of TA-bPEI CDs as a novel nanomaterial for bone regeneration applications.展开更多
NOTCH plays a role in regulating stem cell function and fate decision.It is involved in tooth development and injury repair.Information regarding NOTCH expression in human dental root apical papilla(AP)and its residin...NOTCH plays a role in regulating stem cell function and fate decision.It is involved in tooth development and injury repair.Information regarding NOTCH expression in human dental root apical papilla(AP)and its residing stem cells(SCAP)is limited.Here we investigated the expression of NOTCH3,its ligand JAG1,and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP.Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally.In cultured SCAP,NOTCH3 and JAG1 were co-expressed.Flow cytometry analysis showed that 7%,16%and 98%of the isolated SCAP were positive for NOTCH3,STRO-1 and CD146,respectively with a rare 1.5%subpopulation of SCAP co-expressing all three markers.The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation.Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision.展开更多
文摘Antimicrobial delivery has been advocated for guided tissue regeneration (GTR) or guided bone regeneration (GBR) therapies involving patients with aggressive or unresolved periodontitis/peri-implantitis. Electrospun chitosan membranes demonstrate several advantages over traditional GTR barrier membranes because they stimulate healing, mimic the topology of the extracellular matrix, and allow for diffusion of nutrients and wastes into/out of the graft site, and were shown to stimulate bone formation in a rabbit calvarial criticalsize defect model. Previously, we have shown improvements in mechanical properties and degradation kinetics by crosslinking electrospun membranes with 5 mM or 10 mM genipin. We have also demonstrated the ability of elecrospun chitosan membranes to inhibit lippopolysaccharide (LPS)-induced monocyte activation. In this study, minocycline was incorporated into the chitosan membrane by passive absorption at 5 or 10 mg/mL. The minocycline-loaded membranes and control membranes (carrier only) were tested against Porphyromonas gingivalis (P. gingivalis) by repeated zone of inhibition (ZOI) measurements. Testing showed that uncrosslinked and genipin-crosslinked membranes have similar capacity to absorb aqueous solutions (swelling ratio 1.7 - 2.2). Minocycline loading resulted in bacterial inhibition for up to 8 days from crosslinked membranes (with 11 mm initial ZOI) whereas uncrosslinked membranes loaded with minocycline only inhibited bacteria for 4 days (with 8 mm initial ZOI). These in vitro results suggest that genipin-crosslinked electrospun chitosan membranes loaded with minocycline may be able to reduce early bacterial contamination of GTR graft sites.
文摘Chitosan nanofiber membranes have been known to have a high degree of biocompatibility and support new bone formation with controllable biodegradation. The surface area of these membranes may allow them to serve as local delivery carriers for different biologic mediators. Simvastatin, a drug commonly used for lowering cholesterol, has demonstrated promising bone regenerative capability. The aim of this study was to evaluate simvastatin loaded chitosan nanofiber membranes for guided bone regeneration (GBR) applications and their ability to enhance bone formation in rat calvarial defects. Nanofibrous chitosan membranes with random fiber orientation were fabricated by electrospinning technique and loaded with 0.25 mg of simvastatin under sterile conditions. One membrane was implanted subperiosteally to cover an 8 mm diameter critical size calvarial defect. Two groups: 1) Control: non-loaded chitosan membranes;2) Experimental: chitosan membranes loaded with 0.25 mg of simvastatin were evaluated histologically and via micro-computed tomography (micro-CT) for bone formation at 4 and 8 weeks time points (n = 5/group per time point). Both groups exhibited good biocompatibility with only mild or moderate inflammatory response during the healing process. Histologic and micro-CT evaluations confirmed bone formation in calvarial defects as early as 4 weeks using control and experimental membranes. In addition, newly-formed bony bridges consolidating calvarial defects histologically along with partial radiographic defect coverage were observed at 8 weeks in both groups. Although control and experimental groups demonstrated no significant statistical differences in results of bone formation, biodegradable chitosan nanofiber membranes loaded with simvastatin showed a promising regenerative potential as a barrier material for guided bone regeneration applications.
基金supported by the following funds:the National Research Foundation of Korea(NRF,Daejeon,Republic of Korea)funded by the Korean Government(MSIT,grant no.NRF2018R1A5A2023879 and NRF-2022R1A2C1092088 for H.J.K.)National Research Foundation of Korea(NRF)grant funded by the Korean Government(Ministry of Science and ICT,No.2022R1A2C2005011 for Y.H.K.).
文摘Treating bone defects is a critical challenge in regenerative medicine.Carbon nanomaterials,with their unique physicochemical properties,offer significant potential for enhancing bone regeneration.In this study,we developed tartaric acid(TA)-based carbon dots(CDs)by synthesizing TA with branched polyethyleneimine(bPEI).These TA-bPEI CDs were systematically evaluated to determine their effects on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells(BMSCs)and their capacity to repair calvarial defects in an in vivo model.Characterization of TA-bPEI CDs revealed a size of approximately 10nm and a positive surface charge.The CDs exhibited fluorescence emission peaks between 464 and 506 nm under excitation wavelengths of 340–440nm.Cytotoxicity assays demonstrated that TA-bPEI CDs maintained BMSC viability at concentrations up to 250μg/ml.However,at concentrations of 500μg/ml and above,apoptosis was induced.Treatment with TA-bPEI significantly enhanced osteogenic differentiation in vitro,as evidenced by increased expression of osteogenic-specific proteins such as Runx2,ALP,OCN and OPN.In vivo,the application of TA-bPEI CDs in a mouse calvarial defect model promoted robust new bone formation,reduced defect gaps,and improved bone morphometric parameters,including bone volume fraction and trabecular thickness.These results suggest that TA-bPEI CDs enhance osteogenesis by directly stimulating osteogenic differentiation and upregulating osteogenesis-specific genes.This study demonstrates the high potential of TA-bPEI CDs as a novel nanomaterial for bone regeneration applications.
基金This work was supported in part by a grant from the Emirates Foundation e United Arab Emirates UAE University/NRF Grant and a grant from the National Institutes of Health RO1 DE019156(G.T.-J.H.).The authors deny any conflicts of interest.
文摘NOTCH plays a role in regulating stem cell function and fate decision.It is involved in tooth development and injury repair.Information regarding NOTCH expression in human dental root apical papilla(AP)and its residing stem cells(SCAP)is limited.Here we investigated the expression of NOTCH3,its ligand JAG1,and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP.Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally.In cultured SCAP,NOTCH3 and JAG1 were co-expressed.Flow cytometry analysis showed that 7%,16%and 98%of the isolated SCAP were positive for NOTCH3,STRO-1 and CD146,respectively with a rare 1.5%subpopulation of SCAP co-expressing all three markers.The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation.Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision.
