Junghan Lee, Enkhzaya Davaa, Yixin Jiang, Jung Joo Kim, M. H. Kim, H. An, Jinho Kim, Steve K. Cho, Su-Geun Yang
In this study, we designed combination cancer therapeutic hyaluronan nanoparticles (NIR-responsive ROS-generating pheophorbide A and ROS-cleavable thioketal-linked SN38; PheoA-SN38-HC NPs). And the combined therapeutic effects of PheoA-SN38-HC NPs were investigated against HEY-T30 human ovarian cancer (OC) model which highly co-expresses cancer stem cell (CSC) markers and exhibits strong chemo-resistance. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of CSC markers (CD44, ALDH1A1, and CD117) rather than folic acid receptor is highly associated with poor clinical outcomes in OC patients. Western assay, migration and colony forming assay proved chemo-resistant HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Synthesized NPs were ~250 nm and spherical by DLS and TEM analysis. FACS and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs in CD44+ HEY-T30 cells. Moreover, synergistic effects of the combination therapy of photodynamic ROS generation and ROS-triggered SN38 release were clearly demonstrated with in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 released by ROS-trigger suggested that combination design could compensate for the clinical limitation of photodynamic therapy.
{"title":"Therapeutic Overcoming of Cancer Stem Cell-Featured Chemo-Resistant Ovarian Cancer via Photodynamic Therapy and Cascadic Chemotherapy Combined Hyaluronan Nanoparticles","authors":"Junghan Lee, Enkhzaya Davaa, Yixin Jiang, Jung Joo Kim, M. H. Kim, H. An, Jinho Kim, Steve K. Cho, Su-Geun Yang","doi":"10.2139/ssrn.3873675","DOIUrl":"https://doi.org/10.2139/ssrn.3873675","url":null,"abstract":"In this study, we designed combination cancer therapeutic hyaluronan nanoparticles (NIR-responsive ROS-generating pheophorbide A and ROS-cleavable thioketal-linked SN38; PheoA-SN38-HC NPs). And the combined therapeutic effects of PheoA-SN38-HC NPs were investigated against HEY-T30 human ovarian cancer (OC) model which highly co-expresses cancer stem cell (CSC) markers and exhibits strong chemo-resistance. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of CSC markers (CD44, ALDH1A1, and CD117) rather than folic acid receptor is highly associated with poor clinical outcomes in OC patients. Western assay, migration and colony forming assay proved chemo-resistant HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Synthesized NPs were ~250 nm and spherical by DLS and TEM analysis. FACS and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs in CD44+ HEY-T30 cells. Moreover, synergistic effects of the combination therapy of photodynamic ROS generation and ROS-triggered SN38 release were clearly demonstrated with in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 released by ROS-trigger suggested that combination design could compensate for the clinical limitation of photodynamic therapy.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116784538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Disney, J. Mo, A. Eckersley, A. Bodey, J. Hoyland, M. Sherratt, A. Pitsillides, Peter D. Lee, B. Bay
Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that clinical injury patterns in these tissues occur in localised regions where there is an integrated requirement for both marked compliance and significant load transfer. Here we used synchrotron computed tomography (sCT) to resolve collagen fibre bundles (~5μm width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using intact samples meant that tissue boundaries (such as endplate-disc or nucleus-annulus) and residual strain were preserved; this is vital for characterising both the inherent structure and structural changes upon loading in tissue regions functioning in a near-native environment. Nano-scale displacement measurements along >10,000 individual fibres were tracked, and fibre orientation, curvature and strain changes were compared between the failure-prone posterior-lateral region and the more robust anterior region. These methods can be widely applied to other soft tissues, to identify fibre structures which cause tissue regions to be more susceptible to injury and degeneration. Our results demonstrate for the first time that highly-localised changes in fibre orientation, curvature and strain indicate differences in regional strain transfer and mechanical function (e.g. tissue compliance), correlating directly with locations clinically at risk of damage. This included decreased fibre reorientation at higher loads, specific tissue morphology which reduced capacity for flexibility and high strain at the disc-endplate boundary.
{"title":"In situ Tracking of Individual Collagen Fibre Bundles in Intact Loaded Intervertebral Discs Exposes Damage-Susceptible Collagen Organisations","authors":"C. Disney, J. Mo, A. Eckersley, A. Bodey, J. Hoyland, M. Sherratt, A. Pitsillides, Peter D. Lee, B. Bay","doi":"10.2139/ssrn.3883359","DOIUrl":"https://doi.org/10.2139/ssrn.3883359","url":null,"abstract":"Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that clinical injury patterns in these tissues occur in localised regions where there is an integrated requirement for both marked compliance and significant load transfer. Here we used synchrotron computed tomography (sCT) to resolve collagen fibre bundles (~5μm width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using intact samples meant that tissue boundaries (such as endplate-disc or nucleus-annulus) and residual strain were preserved; this is vital for characterising both the inherent structure and structural changes upon loading in tissue regions functioning in a near-native environment. Nano-scale displacement measurements along >10,000 individual fibres were tracked, and fibre orientation, curvature and strain changes were compared between the failure-prone posterior-lateral region and the more robust anterior region. These methods can be widely applied to other soft tissues, to identify fibre structures which cause tissue regions to be more susceptible to injury and degeneration. Our results demonstrate for the first time that highly-localised changes in fibre orientation, curvature and strain indicate differences in regional strain transfer and mechanical function (e.g. tissue compliance), correlating directly with locations clinically at risk of damage. This included decreased fibre reorientation at higher loads, specific tissue morphology which reduced capacity for flexibility and high strain at the disc-endplate boundary.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123762662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Yu, Yihui Hu, L. Zou, Shifeng Yan, Huimin Zhu, Kunxi Zhang, W. Liuc, D. He, Jingbo Yin
Temporomandibular joint (TMJ) supports chewing, talking or other daily oral activities. So far, it still remains a great challenge to treat the defected TMJ condyle cartilage through tissue engineering technology. Herein, a bilayered gradient scaffold is designed to fully reconstruct the different cartilage matrices of TMJ condyle under same induction condition. The gradient scaffold with segregated hydrophobicity-hydrophilicity in top and bottom layer is prepared from a low and high content of polyethylene glycol (PEG) crosslinked poly (L-glutamic acid)- g -polycaprolactone (PLGA- g -PCL). The hydrophobic microdomains in top layer support the adhesion and spread of bone mesenchymal stem cells (BMSCs), thus inducing the differentation towards fibrocartilage; while aggregates (spheroids) are formed on the hydrophlic bottom layer, showing a preferable hyaline differentiation pathway under same chondrogenic induction in vitro . After 14 d in vitro induction, the scaffold/BMSCs construct is implanted in goat’s TMJ condyle defects. The post-operative outcome after 2 months demonstrates that the defects are fully covered by neo-cartilage , and the regenerated hierarchical TMJ condyle cartilage is perfectly consisted of ordered fibrocartilage and hyaline cartilage, which is same as natural condyle cartilage, corroborating that this gradient scaffold with segregated hydrophilicity-hydrophobicity carrying induced BMSCs is a promising for treatment of TMJ condyle cartilage defects.
颞下颌关节(TMJ)支持咀嚼、说话或其他日常口腔活动。目前，利用组织工程技术治疗TMJ髁突软骨缺损仍然是一个很大的挑战。本文设计了一种双层梯度支架，在相同诱导条件下完全重建TMJ髁的不同软骨基质。以低含量和高含量聚乙二醇(PEG)交联聚(l -谷氨酸)- g -聚己内酯(PLGA- g - pcl)为原料制备了上下两层亲疏分离的梯度支架。顶层疏水微域支持骨间充质干细胞(BMSCs)的粘附和扩散，从而诱导其向纤维软骨分化;而聚集体(球状体)在亲水底层形成，在体外相同的软骨诱导下表现出较好的透明分化途径。体外诱导14 d后，将支架/骨髓间充质干细胞构建物植入山羊TMJ髁突缺损。术后2个月的结果显示缺损被新生软骨完全覆盖，再生的分层状TMJ髁突软骨完全由有序的纤维软骨和透明软骨组成，与天然髁突软骨相同，证实了这种亲疏水分离携带诱导骨髓间充质干细胞的梯度支架是治疗TMJ髁突软骨缺损的一种很有前景的支架。
{"title":"A Gradient Scaffold with Segregated Hydrophilicity-Hydrophobicity Enables Reconstruction of Goat's Hierarchical Temporomandibular Joint Condyle Cartilage","authors":"Xi Yu, Yihui Hu, L. Zou, Shifeng Yan, Huimin Zhu, Kunxi Zhang, W. Liuc, D. He, Jingbo Yin","doi":"10.2139/ssrn.3683634","DOIUrl":"https://doi.org/10.2139/ssrn.3683634","url":null,"abstract":"Temporomandibular joint (TMJ) supports chewing, talking or other daily oral activities. So far, it still remains a great challenge to treat the defected TMJ condyle cartilage through tissue engineering technology. Herein, a bilayered gradient scaffold is designed to fully reconstruct the different cartilage matrices of TMJ condyle under same induction condition. The gradient scaffold with segregated hydrophobicity-hydrophilicity in top and bottom layer is prepared from a low and high content of polyethylene glycol (PEG) crosslinked poly (L-glutamic acid)- g -polycaprolactone (PLGA- g -PCL). The hydrophobic microdomains in top layer support the adhesion and spread of bone mesenchymal stem cells (BMSCs), thus inducing the differentation towards fibrocartilage; while aggregates (spheroids) are formed on the hydrophlic bottom layer, showing a preferable hyaline differentiation pathway under same chondrogenic induction in vitro . After 14 d in vitro induction, the scaffold/BMSCs construct is implanted in goat’s TMJ condyle defects. The post-operative outcome after 2 months demonstrates that the defects are fully covered by neo-cartilage , and the regenerated hierarchical TMJ condyle cartilage is perfectly consisted of ordered fibrocartilage and hyaline cartilage, which is same as natural condyle cartilage, corroborating that this gradient scaffold with segregated hydrophilicity-hydrophobicity carrying induced BMSCs is a promising for treatment of TMJ condyle cartilage defects.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113935537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pathogen-induced sepsis represents the main cause of infection-related death, and is becoming a great threat to human health. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate sepsis. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide (ERP), and a pathogen infection-responsive cap (TPB) containing the reactive oxygen species (ROS)-cleavable boronobenzyl acid linker (TSPBA) and bovine serum albumin (BSA). The TPB-capped MSNs exhibited the capacity to highly load the antimicrobial peptide melittin (MEL), and to rapidly release the cargo triggered by H2O2 or the pathogen-macrophage interaction system. During the interaction between pathogenic C. albicans cells and macrophages, the MEL-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress and secretion of pro-inflammatory cytokines. In a systemic infection model, the nanoplatform efficiently protected the mice from death, prevented kidney dysfunction and alleviated sepsis symptoms. This study developed an efficient multifunctional nanoplatform for treatment of sepsis. Funding Information: This work was supported by National Natural Science Foundation of China (3217010793, 31870139), Natural Science Foundation of Tianjin (19JCZDJC33800), and Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-KJGG-006). Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal experiments were approved by the Animal Care and Use Committee at Nankai University.
{"title":"Pathogen Infection-Responsive Nanoplatform Targeting Macrophage Endoplasmic Reticulum for Alleviating Sepsis","authors":"Yan Zhao, Shuo Liu, Zhishang Shi, Hangqi Zhu, Mingchun Li, Qilin Yu","doi":"10.2139/ssrn.3940189","DOIUrl":"https://doi.org/10.2139/ssrn.3940189","url":null,"abstract":"Pathogen-induced sepsis represents the main cause of infection-related death, and is becoming a great threat to human health. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate sepsis. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide (ERP), and a pathogen infection-responsive cap (TPB) containing the reactive oxygen species (ROS)-cleavable boronobenzyl acid linker (TSPBA) and bovine serum albumin (BSA). The TPB-capped MSNs exhibited the capacity to highly load the antimicrobial peptide melittin (MEL), and to rapidly release the cargo triggered by H2O2 or the pathogen-macrophage interaction system. During the interaction between pathogenic C. albicans cells and macrophages, the MEL-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress and secretion of pro-inflammatory cytokines. In a systemic infection model, the nanoplatform efficiently protected the mice from death, prevented kidney dysfunction and alleviated sepsis symptoms. This study developed an efficient multifunctional nanoplatform for treatment of sepsis. Funding Information: This work was supported by National Natural Science Foundation of China (3217010793, 31870139), Natural Science Foundation of Tianjin (19JCZDJC33800), and Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-KJGG-006). Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal experiments were approved by the Animal Care and Use Committee at Nankai University.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114547840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Paradiso, M. Quintela, S. Lenna, S. Serpelloni, D. James, S. Caserta, R. S. Conlan, L. Francis, F. Taraballi
The complexity of studying a neoplastic disease relies on understanding specialized cell types within the tumor tissue, which can be recruited and ‘corrupted’ to create a dynamic pro-tumorigenic network called the ‘tumor microenvironment’ (TME). Although the TME is of critical importance during initiation and spread of cancer, relatively little is known about its biophysical evolution during tumor development and progression. In this study a 3D collagen type I–based scaffold model cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) was employed to mimic mechanical changes occurring in normal tissue (2 kPa - soft, So) and advanced cancer tissue (12 kPa - stiff, St) and monitor how these biophysical cues affect the stromal tumor compartment. Viability assays, migration patterns and matrix remodeling together with RNA sequencing investigated cancer-associated fibroblasts (CAFs) response to TME stiffness. In the model, CAFs fail to remodel St scaffolds, showing lower migration and increased cell circularity compared to cells grown on So scaffolds. This behavior is reflected in gene expression profiles, showing an upregulation of DNA replication, DNA repair and chromosome organization gene clusters, with a concommitant loss of their ability to remodel and deposit extracellular matrix after culture on St scaffolds. Soft scaffolds can reproduce biophysically-meaningful microenvironements for tumour early stages investigations, while St scaffolds can better mimic mechanical cues occurring in advanced cancer stages. These results not only establish the need for tunable and affordable 3D scaffolds as effective platforms for cancer research but also reveal the contribution of microenvironment biomechanics in regulating gene expression changes in the stromal tumor tissue compartment.
{"title":"Tunable 3D Collagen-Based Scaffolds for Biophysical Tumour Microenvironment Studies","authors":"F. Paradiso, M. Quintela, S. Lenna, S. Serpelloni, D. James, S. Caserta, R. S. Conlan, L. Francis, F. Taraballi","doi":"10.2139/ssrn.3903354","DOIUrl":"https://doi.org/10.2139/ssrn.3903354","url":null,"abstract":"The complexity of studying a neoplastic disease relies on understanding specialized cell types within the tumor tissue, which can be recruited and ‘corrupted’ to create a dynamic pro-tumorigenic network called the ‘tumor microenvironment’ (TME). Although the TME is of critical importance during initiation and spread of cancer, relatively little is known about its biophysical evolution during tumor development and progression. In this study a 3D collagen type I–based scaffold model cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) was employed to mimic mechanical changes occurring in normal tissue (2 kPa - soft, So) and advanced cancer tissue (12 kPa - stiff, St) and monitor how these biophysical cues affect the stromal tumor compartment. Viability assays, migration patterns and matrix remodeling together with RNA sequencing investigated cancer-associated fibroblasts (CAFs) response to TME stiffness. In the model, CAFs fail to remodel St scaffolds, showing lower migration and increased cell circularity compared to cells grown on So scaffolds. This behavior is reflected in gene expression profiles, showing an upregulation of DNA replication, DNA repair and chromosome organization gene clusters, with a concommitant loss of their ability to remodel and deposit extracellular matrix after culture on St scaffolds. Soft scaffolds can reproduce biophysically-meaningful microenvironements for tumour early stages investigations, while St scaffolds can better mimic mechanical cues occurring in advanced cancer stages. These results not only establish the need for tunable and affordable 3D scaffolds as effective platforms for cancer research but also reveal the contribution of microenvironment biomechanics in regulating gene expression changes in the stromal tumor tissue compartment.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127780431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. L. Ramirez-Ledesma, Paola Roncagliolo Barreraa, J. Juarez-Islas,, C. Paternoster, F. Copes, D. Mantovani
Zn is considered as an excellent candidate material for endovascular applications due its outstanding combination of biodegradability and biofunctionality. In the present work, two novel Zn–Ag–Mg alloys with highly desirable mechanical, corrosion, and biological performance are introduced. Microstructural characterization revealed a significant grain refinement as a consequence of alloying (Ag, Mg) in conjunction with an adequate thermomechanical processing route for both alloy systems. Tensile test results indicated that the best mechanical properties in terms of yield strength (YS), ultimate tensile strength (UTS), and elongation to failure (% E) was achieved for the unidirectional rolled (UR) Zn–5.0Ag–0.5Mg alloy (A–1) with values of ~ 300 MPa, ~ 370 MPa, and ~ 40 %, respectively. However, a superior UTS was exhibited for the Zn–10.0Ag–1.0Mg alloy (A–2) with a value of ~ 450 MPa. The observed corrosion rate (CR) trend measured by potentiodynamic polarization test was: A–1 = 2.232 (mm/year) > A–2 = 1.405 (mm/year) > pure Zn = 0.935 (mm/year). When static immersion tests were performed, it was observed a different static corrosion rate (SCR) with the following trend: pure Zn = 0.14 (mm/year) > A–1 = 0.07 (mm/year) > A–2 = 0.05 (mm/year). Moreover, the indirect cell test showed that both alloys exhibited grade 0 of cytotoxicity at 10 % and 1 % of metal extracts. Finally, the proposed alloys showed excellent hemocompatibility characteristics compared to plastic and 316L SS control.
{"title":"Exploring a Novel Bioabsorbable Zn–Ag–Mg Alloy Intended for Cardiovascular Applications","authors":"A. L. Ramirez-Ledesma, Paola Roncagliolo Barreraa, J. Juarez-Islas,, C. Paternoster, F. Copes, D. Mantovani","doi":"10.2139/ssrn.3848998","DOIUrl":"https://doi.org/10.2139/ssrn.3848998","url":null,"abstract":"Zn is considered as an excellent candidate material for endovascular applications due its outstanding combination of biodegradability and biofunctionality. In the present work, two novel Zn–Ag–Mg alloys with highly desirable mechanical, corrosion, and biological performance are introduced. Microstructural characterization revealed a significant grain refinement as a consequence of alloying (Ag, Mg) in conjunction with an adequate thermomechanical processing route for both alloy systems. Tensile test results indicated that the best mechanical properties in terms of yield strength (YS), ultimate tensile strength (UTS), and elongation to failure (% E) was achieved for the unidirectional rolled (UR) Zn–5.0Ag–0.5Mg alloy (A–1) with values of ~ 300 MPa, ~ 370 MPa, and ~ 40 %, respectively. However, a superior UTS was exhibited for the Zn–10.0Ag–1.0Mg alloy (A–2) with a value of ~ 450 MPa. The observed corrosion rate (CR) trend measured by potentiodynamic polarization test was: A–1 = 2.232 (mm/year) > A–2 = 1.405 (mm/year) > pure Zn = 0.935 (mm/year). When static immersion tests were performed, it was observed a different static corrosion rate (SCR) with the following trend: pure Zn = 0.14 (mm/year) > A–1 = 0.07 (mm/year) > A–2 = 0.05 (mm/year). Moreover, the indirect cell test showed that both alloys exhibited grade 0 of cytotoxicity at 10 % and 1 % of metal extracts. Finally, the proposed alloys showed excellent hemocompatibility characteristics compared to plastic and 316L SS control.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122957468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The extracellular matrix (ECM) is the natural microenvironment of stem cells survival, as well as proliferation, differentiation and metastasis, containing a variety of biological molecular complexes secreted by the resident cells in tissues and organs. Heparan sulfate proteoglycans (HSPG) is a major component of ECM, containing one or more covalently attached heparan sulfate chains. The heparan sulphate chains have high affinity with growth factors, chemokines and morphogens, acting as cytokine-binding domains with great importance in development and normal physiology. Herein, lentiviral single-guide RNA vectors were constructed to activate the endogenous HSPG2 expression in mouse embryonic fibroblasts based on CRISPR/Cas9 synergistic activation mediator system, and then HSPG2 functional cell-derived ECM (ECM HSPG2 ) was fabricated. The ECM HSPG2 is capable to enrich cytokines effectively, such as basic fibroblast growth factor (bFGF), which was about 3-flod stronger than binding with negative control ECM. With encapsulating abundant bFGF, ECM HSPG2 could maintain the neural stem cells (NSCs) stemness and promote the NSCs proliferation and differentiation in culture. These findings provide a novel and precise design strategy of smart and special functional cell-derived ECM for the biomaterials research and regenerative medicine.
{"title":"Precise Design Strategy Of Smart Extracellular Matrix Based on CRISPR/Cas9 for Regulating Neural Stem Cell Function","authors":"Yuanxin Zhai, Lingyan Yang, Wenlong Zheng, Quanwei Wang, Zhanchi Zhu, Fangzhu Han, Ying Hao, G. Cheng","doi":"10.2139/ssrn.3890354","DOIUrl":"https://doi.org/10.2139/ssrn.3890354","url":null,"abstract":"The extracellular matrix (ECM) is the natural microenvironment of stem cells survival, as well as proliferation, differentiation and metastasis, containing a variety of biological molecular complexes secreted by the resident cells in tissues and organs. Heparan sulfate proteoglycans (HSPG) is a major component of ECM, containing one or more covalently attached heparan sulfate chains. The heparan sulphate chains have high affinity with growth factors, chemokines and morphogens, acting as cytokine-binding domains with great importance in development and normal physiology. Herein, lentiviral single-guide RNA vectors were constructed to activate the endogenous HSPG2 expression in mouse embryonic fibroblasts based on CRISPR/Cas9 synergistic activation mediator system, and then HSPG2 functional cell-derived ECM (ECM HSPG2 ) was fabricated. The ECM HSPG2 is capable to enrich cytokines effectively, such as basic fibroblast growth factor (bFGF), which was about 3-flod stronger than binding with negative control ECM. With encapsulating abundant bFGF, ECM HSPG2 could maintain the neural stem cells (NSCs) stemness and promote the NSCs proliferation and differentiation in culture. These findings provide a novel and precise design strategy of smart and special functional cell-derived ECM for the biomaterials research and regenerative medicine.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114449073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Khan, Daniel P. Zaki, W. E. Brown, Faris F. Halaseh, Mary E. Ziegler, K. Athanasiou, A. Widgerow
Microtia and anotia are congenital auricular anomalies that negatively impact the psychosocial development of those affected. Because the auricular cartilage is a type of elastic cartilage that lacks regenerative capacity, any notable defect in its structure requires a surgical approach to reconstruct the auricle. While there are several reconstructive options available between alloplastic and prosthetic implants, autologous rib cartilage grafts remain the most commonly used treatment modality. Still, this widely used technique is accompanied by significant patient discomfort in a young child, and it carries additional risks secondary to the traumatic process of rib cartilage extraction, such as pneumothorax, chest wall deformities, and the final aesthetic results may not be ideal. To circumvent these limitations, tissue-engineering approaches have been employed to create a realistic-looking ear that mirrors the complex anatomy of the normal ear. This article provides an overall description of the ear’s anatomy and reviews the traditional management options for auricular reconstruction. The biochemical and biomechanical properties of human auricular cartilage are detailed as they relate to design criteria. In addition, a variety of cell sources, biocompatible scaffolds, scaffold-free techniques, mechanical and biological stimuli have been discussed. This review aims to identify knowledge gaps in the literature related to auricular cartilage characteristics and make recommendations to drive the field of auricular tissue engineering.
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