Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that con...Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals.Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material's responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.展开更多
Tooth decay is prevalent,and secondary caries causes restoration failures,both of which are related to demineralization.There is an urgent need to develop new therapeutic materials with remineralization functions.This...Tooth decay is prevalent,and secondary caries causes restoration failures,both of which are related to demineralization.There is an urgent need to develop new therapeutic materials with remineralization functions.This article represents the first review on the cutting edge research of poly(amido amine)(PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP).PAMAM was excellent nucleation template,and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization.NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities.PAMAM +NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates,superior acidneutralization,and ions release.Therefore,the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone.PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions.Besides,the long-term remineralization capability of PAMAM+NACP was established.After prolonged fluid challenge,the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration.Furthermore,the hardness of predemineralized dentin was increased back to that of healthy dentin,indicating a complete remineralization.Therefore,the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization,hardness increase,and caries-inhibition capabilities.展开更多
Induced pluripotent stem ceils (iPSCs) have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells (iPSC-MSCs),...Induced pluripotent stem ceils (iPSCs) have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells (iPSC-MSCs), and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement (CPC) containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34+ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies (EBs), and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC: RGD (Arg-Gly-Asp) peptides, fibronectin (Fn), fibronectin-like engineered polymer protein (FEPP), extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs: CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.展开更多
Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel b...Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate(DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine(MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent(MPC) and antibacterial agent(DMAHDM) were added to a Scotchbond multi-purpose(SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days(d).At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control(P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control(P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d(P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.展开更多
Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we fo...Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.展开更多
Millions of people worldwide suffer from a toothache due to tooth cavity,and often permanent tooth loss.Dental caries,also known as tooth decay,is a biofilm-dependent infectious disease that damages teeth by minerals ...Millions of people worldwide suffer from a toothache due to tooth cavity,and often permanent tooth loss.Dental caries,also known as tooth decay,is a biofilm-dependent infectious disease that damages teeth by minerals loss and presents a high incidence of clinical restorative polymeric fillings(tooth colored fillings).Until now,restorative polymeric fillings present no bioactivity.The complexity of oral biofilms contributes to the difficulty in developing effective novel dental materials.Nanotechnology has been explored in the development of bioactive dental materials to reduce or modulate the activities of caries-related bacteria.Nano-structured platforms based on calcium phosphate and metallic particles have advanced to impart an anti-caries potential to restorative materials.The bioactivity of these platforms induces prevention of mineral loss of the hard tooth structure and antibacterial activities against caries-related pathogens.It has been suggested that this bioactivity could minimize the incidence of caries around restorations(CARS)and increase the longevity of such filling materials.The last few years witnessed growing numbers of studies on the preparation evaluations of these novel materials.Herein,the caries disease process and the role of pathogenic caries-related biofilm,the increasing incidence of CARS,and the recent efforts employed for incorporation of bioactive nanoparticles in restorative polymer materials as useful strategies for prevention and management of caries-related-bacteria are discussed.We highlight the status of the most advanced and widely explored interaction of nanoparticle-based platforms and calcium phosphate compounds with an eye toward translating the potential of these approaches to the dental clinical reality.展开更多
Peri-implantitis are a major problem causing implant failure these days.Accordingly,anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue.Micro...Peri-implantitis are a major problem causing implant failure these days.Accordingly,anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue.Micro-arc oxidation(MAO)treatment is a way to form an oxidation film on the surface of metallic materials.The method shows good osteogenic properties but weak antibacterial effect.Therefore,we developed combined strategies to combat severe peri-implantitis,which included the use of a novel compound,PD,comprising dendrimers poly(amidoamine)(PAMAM)loading dimethylaminododecyl methacrylate(DMADDM)as well as MAO treatment.Here,we explored the chemical properties of the novel compound PD,and proved that this compound was successfully synthesized,with the loading efficiency and encapsulation efficiency of 23.91%and 31.42%,respectively.We further report the two-stage double benefits capability of PD+MAO:(1)in the first stage,PD+MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo;(2)in the second stage,PD+MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo.This study first reports the two-staged,double benefits of PD+MAO,and demonstrates its potential in clinical applications for inhibiting peri-implantitis,especially in patients with severe infection risk.展开更多
The utilization of Calcium Phosphate Cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the scaffold.The objectives of this study were to:(1)develop a 3D-printed CPC-dopami...The utilization of Calcium Phosphate Cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the scaffold.The objectives of this study were to:(1)develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells(hPDLSCs),(2)investigate the effect of dopamine on the performance of CPC,and(3)evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released hPDLSCs.The mechanical property of the CPC scaffolds was elevated by adding dopamine,and the CPC scaffold with 7 wt.%dopamine had the highest compressive strength(7.35 MPa).Four types of microbeads with different content of alginate(oxidized alginate),hPDLSCs,and 2%metformin were fabricated.Morphological and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting process.The alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and metformin.The microbeads consisting of 2%oxidized alginate and 2%metformin were optimal for cell delivery due to favorable cell release and osteogenic differentiation.This CPC scaffold is promising used for bone regeneration in dental,craniofacial,and orthopedic applications.展开更多
基金supported by NIH R01DE17974 (H.H.K.X.),NIH U01DE023752 (J.S.)International Science and Technology Programme 2017HH0008 (L.C.)+4 种基金National Natural Science Foundation of China NSFC 81400540 (K.Z.)Beijing Municipal Administration of Hospitals’ Youth Programme QML20151401 (K.Z.)NSFC 81500879 (N.Z.)Nova Programme xx2014B060 (X.X.)University of Maryland Dental School Bridging Fund (H.H.K.X.)
文摘Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals.Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material's responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.
基金supported by National Natural Science Foundation of China (81670977, J.L. and 81800965, K.L.)Sichuan Science and Technology program (Grant no. 2017SZ0030)+5 种基金Fundamental Research Funds for Central University 2018SCU12016 (K.L.)China Postdoctoral Science Grant 2018M643507 (K.L.)Research Fund of West China Hospital WCHS-201705 (K.L.)Research Fund for Resins of Chinese Stomatological Association CSA-R2018-06 (K.L.)University of Maryland School of Dentistry bridging fund (H.H.K.X.)University of Maryland Baltimore seed grant (H.H.K.X.)
文摘Tooth decay is prevalent,and secondary caries causes restoration failures,both of which are related to demineralization.There is an urgent need to develop new therapeutic materials with remineralization functions.This article represents the first review on the cutting edge research of poly(amido amine)(PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP).PAMAM was excellent nucleation template,and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization.NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities.PAMAM +NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates,superior acidneutralization,and ions release.Therefore,the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone.PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions.Besides,the long-term remineralization capability of PAMAM+NACP was established.After prolonged fluid challenge,the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration.Furthermore,the hardness of predemineralized dentin was increased back to that of healthy dentin,indicating a complete remineralization.Therefore,the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization,hardness increase,and caries-inhibition capabilities.
基金supported by NIH R01 DE14190(HX),R21 DE22625(HX)and R01 HL-073781(LC)the University of Maryland School of Dentistry startup fund(HX)
文摘Induced pluripotent stem ceils (iPSCs) have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells (iPSC-MSCs), and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement (CPC) containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34+ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies (EBs), and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC: RGD (Arg-Gly-Asp) peptides, fibronectin (Fn), fibronectin-like engineered polymer protein (FEPP), extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs: CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.
基金the Natural Science Foundation of China NSFC 81500879(N.Z.),81400540(K.Z.)the Beijing Municipal Science and Technology Commission Z151100003915137(N.Z.)+2 种基金the Beijing Municipal Administration of Hospitals’YouthProgram QML20161501(N.Z.),QML20151401(K.Z.)the Beijing Municipal Hospitals’Program ZYLX201703(Y.B.),NIH R01 DE17974(H.X.)a Seed Grant(H.X.)from the University of Maryland School of Dentistry
文摘Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate(DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine(MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent(MPC) and antibacterial agent(DMAHDM) were added to a Scotchbond multi-purpose(SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days(d).At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control(P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control(P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d(P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81873713,81670984,81873829,and 81700959)the International Cooperation Project of Science and Technology in Guangdong Province(Grant No.2016B050502008).
文摘Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.
文摘Millions of people worldwide suffer from a toothache due to tooth cavity,and often permanent tooth loss.Dental caries,also known as tooth decay,is a biofilm-dependent infectious disease that damages teeth by minerals loss and presents a high incidence of clinical restorative polymeric fillings(tooth colored fillings).Until now,restorative polymeric fillings present no bioactivity.The complexity of oral biofilms contributes to the difficulty in developing effective novel dental materials.Nanotechnology has been explored in the development of bioactive dental materials to reduce or modulate the activities of caries-related bacteria.Nano-structured platforms based on calcium phosphate and metallic particles have advanced to impart an anti-caries potential to restorative materials.The bioactivity of these platforms induces prevention of mineral loss of the hard tooth structure and antibacterial activities against caries-related pathogens.It has been suggested that this bioactivity could minimize the incidence of caries around restorations(CARS)and increase the longevity of such filling materials.The last few years witnessed growing numbers of studies on the preparation evaluations of these novel materials.Herein,the caries disease process and the role of pathogenic caries-related biofilm,the increasing incidence of CARS,and the recent efforts employed for incorporation of bioactive nanoparticles in restorative polymer materials as useful strategies for prevention and management of caries-related-bacteria are discussed.We highlight the status of the most advanced and widely explored interaction of nanoparticle-based platforms and calcium phosphate compounds with an eye toward translating the potential of these approaches to the dental clinical reality.
基金This research was supported by the National Key Research and Development Program of China(2016YFC1102700,2016YFC1102701 X.Z)National Natural Science Foundation of China(81870759,82071106,L.C)Innovative Research Team Program of Sichuan Province(L.C).
文摘Peri-implantitis are a major problem causing implant failure these days.Accordingly,anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue.Micro-arc oxidation(MAO)treatment is a way to form an oxidation film on the surface of metallic materials.The method shows good osteogenic properties but weak antibacterial effect.Therefore,we developed combined strategies to combat severe peri-implantitis,which included the use of a novel compound,PD,comprising dendrimers poly(amidoamine)(PAMAM)loading dimethylaminododecyl methacrylate(DMADDM)as well as MAO treatment.Here,we explored the chemical properties of the novel compound PD,and proved that this compound was successfully synthesized,with the loading efficiency and encapsulation efficiency of 23.91%and 31.42%,respectively.We further report the two-stage double benefits capability of PD+MAO:(1)in the first stage,PD+MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo;(2)in the second stage,PD+MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo.This study first reports the two-staged,double benefits of PD+MAO,and demonstrates its potential in clinical applications for inhibiting peri-implantitis,especially in patients with severe infection risk.
基金National Natural Science Foundation of China(Grant No.52035012)Fundamental Research Funds for the Central Universities(2682020ZT91)+1 种基金Basic Research Foundation Key Project of Sichuan Province(2021JY0046)Basic Research Foundation of Sichuan Province(2022JDRC0088).
文摘The utilization of Calcium Phosphate Cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the scaffold.The objectives of this study were to:(1)develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells(hPDLSCs),(2)investigate the effect of dopamine on the performance of CPC,and(3)evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released hPDLSCs.The mechanical property of the CPC scaffolds was elevated by adding dopamine,and the CPC scaffold with 7 wt.%dopamine had the highest compressive strength(7.35 MPa).Four types of microbeads with different content of alginate(oxidized alginate),hPDLSCs,and 2%metformin were fabricated.Morphological and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting process.The alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and metformin.The microbeads consisting of 2%oxidized alginate and 2%metformin were optimal for cell delivery due to favorable cell release and osteogenic differentiation.This CPC scaffold is promising used for bone regeneration in dental,craniofacial,and orthopedic applications.