查看更多>>摘要：Differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been recently disclosed to play a pivotal role in stem cell differentiation.However,it remains elusive how viscosity affects the chondrogenic differentiation of hMSCs during three-dimensional (3D) culture.In this study,a 3D culture system that was established by embedding viscous gelatin solution in chemically cross-linked gelatin hydrogels was used for 3D culture of hMSCs in gelatin solutions with different viscosities.The influence of solution viscosity on chondrogenic differentiation of hMSCs was investigated.Viscous gelatin solutions promoted cell proliferation in the order of low,middle and high viscosity while elastic hydrogels restricted cell proliferation.High viscosity gelatin solution led to increased production of the cartilaginous matrix.Under the synergistic stimulation ofchondrogenic induction factors,high viscosity was beneficial for the chondrogenic differentiation of hMSCs.The results suggested the role of viscosity should be considered as one of the dominant mechanical cues affecting stem cell differentiation.
查看更多>>摘要：Human mesenchymal stem cells,such as human adipose-derived stem cells (hASCs),are typically cultured on a two-dimensional (2D) monolayer material surface,on which 2D culturing methods are easily performed and time-saving.However,hASCs usually suffer from decreased pluripotency and differentiation ability when cultured with a 2D monolayer culturing method compared to hASCs cultured with a three-dimensional (3D) culturing method,such as suspension culture.In this study,we evaluated whether the pluripotency and differentiation ability of hASCs can be reversibly changed during sequential cultivation with 2D and 3D culturing processes.The hASCs cultivated with a 3D culturing process after 2D culture showed at least 2-fold enhanced pluripotency (Sox2,Nanog,and OCT4) compared with that of hASCs cultured with the 2D culture process alone.Furthermore,hASCs obtained from the 3D culture process expressed increased levels of differentiation markers of chondrocytes and osteoblasts compared with hASCs obtained from the 2D culture process when hASCs were induced to differentiate.However,their pluripotency and differentiation ability were extensively reduced when hASCs were shifted from 3D culture to 2D culture and vice versa,which indicates that hASCs show reversibility in terms of their pluripotency and differentiation ability depending on their environment in 2D and 3D culture.The reversibility of pluripotency and differentiation ability were found to last for at least 5 passages in culture during the alternative and sequential culture of cells with 2D and 3D culturing processes.Our study revealed the importance of the culture microenvironment in maintaining the pluripotency and differentiation ability of hASCs,which may reduce the effects of the aging process in hASCs.We discuss whether the environment of stem cell culture (i.e.,2D or 3D cultivation) can affect stem cell fate in terms of pluripotency and differentiation reversibility.
查看更多>>摘要：Personalized precision therapy and rapid osseointegration are the main development directions of dental implants.3D printing is a vital advanced manufacturing technology for personalized precision therapy.However,the osteogenesis of the 3D printed Ti6Al4V implants is unsatisfactory.From the bionic perspective,the hierarchical micro/nano-topography can mimic the microenvironment of the multilevel structure of natural bone tissue and may endow the implant surface with superior bioactivity.In the present study,the hierarchical micro/nano-topography was successfully fabricated by construction the nanoscale feature on 3D printed microscale roughness surface of 3D-printed Ti6Al4V implants by alkali-heat treatment and hydrothermal treatment.Then the cell biological responses in vitro and osseointegration performance in vivo were systematically evaluated.The hierarchical micro/nano-topography evidently increased the roughness,improved the hydrophilicity and accelerated the hydroxyapatite deposition and mineralization,which significantly enhanced the adhesion,differentiation and extracellular matrix mineralization of bone marrow derived mesenchymal stromal cells (BMSCs).Most importantly,the hierarchical micro/nano-topography on 3D-printed implants facilitated the new bone formation and rapid osseointegration in vivo.Our study suggested that 3D-printed implant with micro/nano-topography may be a promising candidate to be applied in orthopedic field to meet the need of customized therapy and rapid osseointegration.
Yon Jin ChuahYingnan WuMei Ling Shirlynn CheongYan Qing Chia...
27-34页
查看更多>>摘要：Low back pain associated with degenerative disc diseases has been a major health concern that brings suffering to the patients physically and economically.Many existing therapeutic strategies provide short-term relief of symptoms rather than treatment of the underlying cause.Development of an engineered tissue for disc regeneration is still in its infancy due to the limited autologous healthy disc cell source from the patients.It is also challenging to mimic the complexity of micro-architecture in the native disc tissue that determine their unique structural properties.To date,simple tissue models that mimic the annulus fibrosus (AF) micro-environment for understanding the potential of mesenchymal stem cells (MSCs) in AF tissue engineering are still lacking.In this study,the assembly of a coiled hydrogel microfiber has shown its capability to encapsulate MSCs and create an engineered tissue model that mimics the multiple lamellae of native AF.Using this model,we investigated the potential of MSCs that were previously induced by ascorbic acid (AA).Compared to non-induced MSCs,AA-induced MSCs exhibited significant increase in AF-associated biomarkers during later development in the engineered AF tissue model and also encouraged collagen accumulation through the down-regulated catabolic gene MMP1 and upregulated anti-catabolic gene TIMP1.Furthermore,AA-induced MSCs exhibited a Col2/Col1 ratio closer to that of a native AF tissue.These results suggested that AA-induced MSCs could be a potential cell source for AF tissue engineering and this established tissue model may provide a simple tool for successful AF tissue engineering strategies in the future.
查看更多>>摘要：Recently,the metal ion cross-linked hydrogels have gained enormous interest because of its excellent properties like self-healing,fast recovery,biocompatibility and high mechanical properties combined with multi-stimuli responsiveness.In this review article,we have summarized the recent trends in the development of metal ion cross-linked hydrogels for tissue engineering and biomedical applications.A number of metal ions and their contribution in the synthesis of various cross-linked hydrogels are discussed with respect to their crosslinking mechanisms,compositions,physio-chemical and biological properties.A special emphasis has been given to ferric (Fe3+) ion cross-linked hydrogels and their different combinations owing to their numerous researches reported in the recent past with exceptional properties.The application of these metal ion based hydrogels in biomedical applications including tissue engineering,sensing,wound healing,drug delivery and as tissue adhesive and tissue sealants are reviewed with specific examples.Importantly,the application of these metal ion cross-linked hydrogels as inks in 3D printing is explained in a separate section.Finally,the possible toxic effects of the different metal ions and their effects have been scrutinized.Future directions and comprehensive applications of the hydrogels are highlighted.
查看更多>>摘要：To advance organ-on-a-chip development and other areas befitting from physiologically-relevant biomembranes,a microfluidic platform is presented for synthesis of biomembranes during gelation and investigation into their role as extracellular matrix supports.In this work,high-throughput studies of collagen,chitosan,and collagen-chitosan hybrid biomembranes were carried out to characterize and compare key properties as a function of the applied hydrodynamic conditions during gelation.Specifically,depending on the biopolymer material used,varying flow conditions during biomembrane gelation caused width,uniformity,and swelling ratio to be differently affected and controllable.Finally,cell viability studies of seeded fibroblasts were conducted,thus showing the potential for biological applications.
查看更多>>摘要：The facts that most tissues or organs consist of a variety of cells suggest that interactions between different types of cells play critical roles in tissue or organ development.In tissue engineering,the effects of biomaterials on cell-cell interactions have recently attracted increasing attention for better elucidating the mechanisms through which biomaterials promote tissue regeneration.Numerous studies have focused on these effects of biomaterials on cell-cell interactions.In this review,comprehensive information was provided about the existing cell co-culture technologies and the main behavioral modes of cell-cell interactions.The effects of biomaterials on the cell-cell interactions in various types of tissue regeneration have been summarized and discussed.In the end,the existing problems and future perspectives that would help promote the research of biomaterials in tissue engineering have been proposed.This article can help researchers to understand the progress and importance of studying the effects of biomaterials on cell-cell interactions in tissue engineering and to choose the optimal cell-cell co-culture models for designing experiments.
查看更多>>摘要：Breast cancer is the most common one in women worldwide and doxorubicin (Dox) is one of the most commonly used and effective drugs for breast cancer treatment.Unfortunately,Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency.It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment,in this work,a multifunctional calcium phosphate nanoformulation (ICG-Dox/DNA@CaP) was developed by co-loading Dox/DNA complexes and indocyanine green (ICG) molecules for photothermal therapy (PTT)-enhanced chemotherapy.In this nanocomposite,using DNA as Dox carrier facilitated Dox loading into the CaP matrix,and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium (pH 7.4).In specific,ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment,such as tumor microenvironment and endosome/lysosome.Moreover,Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite.This work has demonstrated a new strategy to combine FDA-approved therapeutics (Dox and ICG) in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect,and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.
查看更多>>摘要：The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma therapy.In this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods (D/R@Ang2-Lip + Au) simultaneously,which has high encapsulating efficiency for doxorubicin (95.4 ％) and effective binding of siRNA at N/P ratio of 20∶1.The fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip + Au.Real-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip + Au could effectively inhibit the expression of YAP protein.In vitro and in vivo studies showed that D/R@Ang2-Lip + Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip + Au.Moreover,in vivo experiment demonstrated that D/R@Ang2-Lip + Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor growth.Therefore,the multifunctional D/R@Ang2-Lip + Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.
查看更多>>摘要：Functionalization of mesoporous silica spheres with well-dispersed and ultra-small nanodots to exert their synergistic effects for biomedical applications has been considered to be an urgent challenge.Herein,homogeneously incorporation of ultra-small and monodispersed MoS2 nanodots in the mesoporous silica nanospheres (MSN) was achieved by a facile one-step solvothermal reaction.The as-synthesized UsM-SND@MSN possessed uniform size (～115 nm) and favorable biocompatibility inherited from MSN.The dispersed UsMSND within MSN could act as anchoring sites for aromatic anti-cancer drug DOX loading,and consequently achieved pH-responsive release based on the special π-π/electrostatic interactions with the DOX molecules.More importantly,the well-dispersed UsMSND in MSN could function as the non-toxic contrast agent for the sensitive in vivo CT imaging in various tumors including breast cancer and glioma with different sections.This work promises a good strategy for dispersed incorporation of UsMSND into MSN as an excellent pH-responsive platform for simultaneous cancer imaging and therapy.
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