ChemRN: Biomaterials (Topic)最新文献

{"title":"High Throughput Interrogation of Human Liver Stellate Cells Reveals Microenvironmental Regulation of Phenotype","authors":"Aidan Brougham-Cook, Ishita Jain, David A. Kukla, Faisal Masood, Hannah R C Kimmel, Hyeon Ryoo, S. Khetani, Gregory H. Underhill","doi":"10.2139/ssrn.3855767","DOIUrl":"https://doi.org/10.2139/ssrn.3855767","url":null,"abstract":"Liver fibrosis is a common feature of progressive liver disease and is manifested as a dynamic series of alterations in both the biochemical and biophysical properties of the liver. Hepatic stellate cells (HSCs) reside within the perisinusoidal space of the liver sinusoid and are one of the main drivers of liver fibrosis, yet it remains unclear how changes to the sinusoidal microenvironment impact HSC phenotype in the context of liver fibrosis. Cellular microarrays were used to examine and deconstruct the impacts of bio-chemo-mechanical changes on activated HSCs in vitro. Extracellular matrix (ECM) composition and stiffness were found to act individually and in combination to regulate HSC fibrogenic phenotype and proliferation. Hyaluronic acid and collagen III promoted elevated collagen I expression while collagen IV mediated a decrease. Previously activated HSCs exhibited reduced lysyl oxidase (Lox) expression as array substrate stiffness increased, with less dependence on ECM composition. Collagens III and IV increased HSC proliferation, whereas hyaluronic acid had the opposite effect. Meta-analysis performed on these data revealed distinct phenotypic clusters (e.g. low fibrogenesis/high proliferation) as a direct function of their microenvironmental composition. Notably, soft microenvironments mimicking healthy tissue (1 kPa), promoted higher levels of intracellular collagen I and Lox expression in activated HSCs, compared to stiff microenvironments mimicking fibrotic tissue (25 kPa). Collectively, these data suggest potential HSC functional adaptations in response to specific bio-chemo-mechanical changes relevant towards the development of therapeutic interventions. These findings also underscore the importance of the microenvironment when interrogating HSC behavior in healthy, disease, and treatment settings. STATEMENT OF SIGNIFICANCE: : In this work we utilized high-throughput cellular microarray technology to systematically interrogate the complex interactions between HSCs and their microenvironment in the context of liver fibrosis. We observed that HSC phenotype is regulated by ECM composition and stiffness, and that these phenotypes can be classified into distinct clusters based on their microenvironmental context. Moreover, the range of these phenotypic responses to microenvironmental stimuli is substantial and a direct consequence of the combinatorial pairing of ECM protein and stiffness signals. We also observed a novel role for microenvironmental context in affecting HSC responses to potential fibrosis therapeutics.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114638882","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}

{"title":"Micro-Groove Patterned PCL Patches with DOPA for Rat Achilles Tendon Regeneration","authors":"Sihyeon Park, Min Suk Lee, Jin Jeon, Juhan Lim, C. Jo, H. Yang","doi":"10.2139/ssrn.3855766","DOIUrl":"https://doi.org/10.2139/ssrn.3855766","url":null,"abstract":"Abstract Achilles tendon regeneration using current tissue engineering techniques requires morphometrically mimetic tendon biomaterials to attain the required microstructural tendon tissue and to achieve the necessary mechanical properties. In this study, we used nano- (400 nm) and micro-groove (5000 nm) patterned polycaprolactone patches (PCL-400, PCL-5000), which offer adequate elastic modulus and biocompatibility. The PCL patches were fabricated via capillary force lithography and were surface modified with 3,4-dihydroxy-L-phenylalanine (DOPA) for increased hydrophilicity. We hypothesized that the resulting biologically surface-modified elastic groove patterned patches would enhance the cell behaviors in vitro and the rat Achilles tendon regeneration in vivo. The micro-groove patterned PCL patches with DOPA coating (DOPA-PCL-5000) exhibited excellent cell elongation, tenogenic differentiation and YAP expression of the mesenchymal stem cells in our in vitro study and these results were further confirmed by application to the rat Achilles tendon rupture model in our in vivo study. DOPA-PCL-5000 induced dramatic regeneration of rat Achilles tendon compared to the other groups, which was further confirmed by the Achilles functional index and histological analysis at 8 weeks. In conclusion, DOPA-PCL-5000 can be used not only for damaged Achilles tendon, but also for various functional tendon regeneration techniques such as rotator cuff, patellar tendon, and flexor tendon.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125187072","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}

{"title":"TGF-β3-Loaded Graphene Oxide - Self-Assembling Peptide Hybrid Hydrogels as Functional 3D Scaffolds for the Regeneration of the Nucleus Pulposus","authors":"C. Ligorio, Marie O'Brien, N. Hodson, Aleksandr Mironov, Maria Iliut, A. Miller, A. Vijayaraghavan, J. Hoyland, A. Saiani","doi":"10.2139/ssrn.3777628","DOIUrl":"https://doi.org/10.2139/ssrn.3777628","url":null,"abstract":"Intervertebral disc (IVD) degeneration is a process that starts in the central nucleus pulposus (NP) and leads to inflammation, extracellular matrix (ECM) degradation, and progressive loss of disc height. Early treatment of IVD degeneration is critical to the reduction of low back pain and related disability. As such, minimally invasive therapeutic approaches that can halt and reverse NP degeneration at the early stages of the disease are needed. Recently, we developed an injectable graphene oxide (GO) - self-assembling peptide FEFKFEFK (F: phenylalanine; K: lysine; E: glutamic acid) hybrid hydrogels as potential delivery platform for cells and/or drugs in the NP. In this current study, we explored the possibility of using the GO present in these hybrid hydrogels as a vehicle for the sequestration and controlled delivery of transforming growth factor beta-3 (TGF-β3), an anabolic growth factor (GF) known to direct NP cell fate and function. For this purpose, we first investigated the potential of GO to bind and sequestrate TGF-β3. We then cultured bovine NP cells in the new functional scaffolds and investigated their response to the presence of GO and TGF-β3. Our results clearly showed that GO flakes can sequestrate TGF-β3 through strong binding interactions resulting in a slow and prolonged release with the GF remaining active even when bound to the GO flakes. The adsorption of the GF on the GO flakes to create TGF-β3-loaded GO flakes and their subsequent incorporation in the hydrogels through mixing, [(GO/TGF-β3Ads)-F8] hydrogel, led to the upregulation of NP-specific genes, accompanied by the production and deposition of an NP-like ECM, rich in aggrecan and collagen II. NP cells actively interacted with TGF-β3-loaded GO flakes and remodeled the scaffolds through endocytosis. This work highlights the potential of using GO as a nanocarrier for the design of functional hybrid peptide-based hydrogels. STATEMENT OF SIGNIFICANCE: : Intervertebral disc (IVD) degeneration is a process that starts in the central nucleus pulposus (NP) and leads to inflammation, extracellular matrix (ECM) degradation, and progressive loss of disc height. As such, minimally invasive therapeutic approaches that can halt and reverse NP degeneration at the early stages of the disease are needed. In this current study, we explored the possibility of using peptide - GO hybrid hydrogels as a vehicle for the sequestration and controlled delivery of transforming growth factor beta-3 (TGF-β3), an anabolic growth factor (GF) known to direct NP cell fate and function.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126721630","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}

{"title":"Three-Dimensional Bioprinting of a Full-Thickness Functional Skin Model Using Acellular Dermal Matrix and Gelatine Methacrylamide Bioink","authors":"R. Jin, Yuecheng Cui, Haojiao Chen, Zhenzhen Zhang, T. Weng, S. Xia, Meirong Yu, Wei Zhang, J. Shao, Min Yang, Chunmao Han, Xingang Wang","doi":"10.2139/ssrn.3814585","DOIUrl":"https://doi.org/10.2139/ssrn.3814585","url":null,"abstract":"Treatment of full-thickness skin defects still presents a significant challenge in clinical practice. Three-dimensional (3D) bioprinting technique offers a promising approach for fabricating skin substitutes. However, it is necessary to identify bioinks that have both sufficient mechanical properties and desirable biocompatibilities. In this study, we successfully fabricated acellular dermal matrix (ADM) and gelatin methacrylamide (GelMA) bioinks. The results demonstrated that ADM preserved the main extracellular matrix (ECM) components of the skin and GelMA had tunable mechanical properties. Both bioinks with shear-thinning properties were suitable for 3D bioprinting and GelMA bioink exhibited high printability. Additionally, the results revealed that 20% GelMA with sufficient mechanical properties was suitable to engineer epidermis, 1.5% ADM and 10% GelMA displayed relatively good cytocompatibilities. Here, we proposed a new 3D structure to simulate natural full-thickness skin, which included 20% GelMA with HaCaTs as an epidermal layer, 1.5% ADM with fibroblasts as the dermis, and 10% GelMA mesh with human umbilical vein endothelial cells (HUVECs) as the vascular network and framework. We demonstrated that this 3D bioprinting functional skin model (FSM) could not only promote cell viability and proliferation, but also support epidermis reconstruction in vitro. When transplanted in vivo, the FSM could maintain cell viability for at least 1 week. Furthermore, the FSM promoted wound healing and re-epithelization, stimulated dermal ECM secretion and angiogenesis, and improved wound healing quality. The FSM may provide viable functional skin substitutes for future clinical applications.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130200427","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}

{"title":"Collagen Networks within 3D PEG Hydrogels Support Valvular Interstitial Cell Matrix Mineralization","authors":"M. E. Schroeder, Andrea Gonzalez Rodriguez, Kelly F Speckl, Cierra J. Walker, Firaol S. Midekssa, Joseph C. Grim, R. Weiss, K. Anseth","doi":"10.2139/ssrn.3677406","DOIUrl":"https://doi.org/10.2139/ssrn.3677406","url":null,"abstract":"Enzymatically degradable hydrogels were designed for the 3D culture of valvular interstitial cells (VICs), and through the incorporation of various functionalities, we aimed to investigate the role of the tissue microenvironment in promoting the osteogenic properties of VICs and matrix mineralization. Specifically, porcine VICs were encapsulated in a poly(ethylene glycol) hydrogel crosslinked with a matrix metalloproteinase (MMP)-degradable crosslinker (KCGPQG↓IWGQCK) and formed via a thiol-ene photoclick reaction in the presence or absence of collagen type I to promote matrix mineralization. VIC-laden hydrogels were treated with osteogenic medium for up to 15 days, and the osteogenic response was characterized by the expression of RUNX2 as an early marker of an osteoblast-like phenotype, osteocalcin (OCN) as a marker of a mature osteoblast-like phenotype, and vimentin (VIM) as a marker of the fibroblast phenotype. In addition, matrix mineralization was characterized histologically with Von Kossa stain for calcium phosphate. Osteogenic response was further characterized biochemically with calcium assays, and physically via optical density measurements. When the osteogenic medium was supplemented with calcium chloride, OCN expression was upregulated and mineralization was discernable at 12 days of culture. Finally, this platform was used to screen various drug therapeutics that were assessed for their efficacy in preventing mineralization using optical density as a higher throughput read out. Collectively, these results suggest that matrix composition has a key role in supporting mineralization deposition within diseased valve tissue.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134193996","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}

{"title":"Advanced Materials for Drug Delivery Across Mucosal Barrier","authors":"Sony Priyanka Bandi, Shubhmita Bhatnagar, V. V. Venuganti, V. V. Venuganti","doi":"10.2139/ssrn.3674136","DOIUrl":"https://doi.org/10.2139/ssrn.3674136","url":null,"abstract":"Mucus is a viscoelastic gel that traps pathogens and other foreign particles to limit their penetration into the underlying epithelium. Dosage forms containing particle-based drug delivery systems are trapped in mucosal layers and will be removed by mucus turnover. Mucoadhesion avoids premature wash-off and prolongs the residence time of drugs on mucus. Moreover, mucus penetration is essential for molecules to access the underlying epithelial tissues. Various strategies have been investigated to achieve mucoadhesion and mucus penetration of drug carriers. Innovations in materials used for the construction of drug-carrier systems allowed the development of different mucoadhesion and mucus penetration delivery systems. Over the last decade, advances in the field of materials chemistry, with a focus on biocompatibility, has led to the expansion of the pool of materials available for drug delivery applications. The choice of materials in mucosal delivery is generally dependent on the intended therapeutic target, properties of pathological features of the mucosa, among others. This review presents an up-to-date account of materials including synthesis, physical and chemical modifications of mucoadhesive materials, nanocarriers, viral mimics used for the construction of mucosal drug delivery systems.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131257892","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}

{"title":"Strontium Regulates Stem Cells Fates During Osteogenic Differentiation Through an Asymmetric Cell Division","authors":"Yanqun Li, Jianhui Yue, Yuan Liu, Jun Wu, Min Guan, Di Chen, H. Pan, Zhao, W. Lu","doi":"10.2139/ssrn.3640693","DOIUrl":"https://doi.org/10.2139/ssrn.3640693","url":null,"abstract":"Strontium as a popular osteogenic component has been incorporated into various types of orthopaedic biomaterials to enhance bone regeneration. It performs dual effects in promoting bone formation and inhibiting bone resorption. Studies have focused on the effects of strontium in regulating stem cells behaviors to initiate regenerative capacity. However, the mechanism of strontium on regulating stem cells fates and homeostasis has not been fully elucidated. In this study, the promoted effect of strontium on osteogenic differentiation of mesenchymal stem cells was confirmed both in vitro and in vivo. Interestingly, in responding to strontium treatment, stem cells performed asymmetric cell division to balance stemness maintenance and osteogenic differentiation. Asymmetric distribution of Par complex in daughter stem cells induced different cell fates by discriminately activating of osteogenic transcription factors. Strontium activated noncanonical Wnt signaling to regulate Par complex distribution. Understanding the mechanism of strontium on regulating stem cell fate could facilitate biomaterials designing to initiate endogenous bone regenerative capacity.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121057176","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}

{"title":"A Comparison of Anticancer Activities of Copper Nanoparticles on Two Cancer Lung Cell Lines","authors":"Zeid A. Alothman, Ahmad Yacine Badjah, I. Ali","doi":"10.2139/SSRN.3619090","DOIUrl":"https://doi.org/10.2139/SSRN.3619090","url":null,"abstract":"Due to the need of nano-medicines, the efforts are made to synthesize copper oxide nanoparticles from copper sulphate and copper acetate. These were characterized by the different spectroscopic techniques and showed rough surface with particle sizes 20 to 50 nm (from copper sulphate) and 21 to 51.5 nm (from copper acetate). The anticancer activities were assessed by change in morphology, DAPI staining and MTT assay with A549 and H1299 cell lines. Profound effects of the reported nanoparticles on the morphology were observed. DAPI staining confirmed changes in cells apoptotic morphological structures, chromatin compression, nuclear reduction and apoptotic bodies formation. MTT assay confirmed anticancer activities 59 to 68% for both nanoparticles. It was observed that nanoparticles obtained from copper sulphate showed slightly higher anticancer activities than nanoparticles obtained from copper acetate. Finally, it was concluded that the reported nanoparticles may be used for future anticancer medication as nano anti-cancer drugs.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126876379","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}

{"title":"Substrate Stiffness Regulated Regulatory Volume Decrease (RVD) and Calcium Signaling of Chondrocyte","authors":"Quanyou Zhang, Xiao-na Liu, Xiaoan Wu, Genlai Du, Jia-Dong Bai, Min Zhang, Xiaochun Wei, Wei-yi Chen","doi":"10.2139/ssrn.3568117","DOIUrl":"https://doi.org/10.2139/ssrn.3568117","url":null,"abstract":"Substrate stiffness is an important physical cue of the microenvironment and plays a critical role in transducing biochemical and biomechanical signals for chondrocytes. But how substrate stiffness modulates the chondrocyte volume and calcium signaling remains unknown. This study aims to recapitulate the physiologically relevant stiffness and to investigate the effects of substrate stiffness on the chondrocyte regulatory volume decrease (RVD) and calcium signaling. The mechanical properties of chondrocytes on varying substrate stiffness in both iso-osmotic and hypo-osmotic medium were measured by using atomic force microscopy (AFM). The cell diameter rate during the RVD response was measured. TRPV4-mediated calcium signaling of chondrocytes was captured by calcium dye solution. TRPV4 protein and mRNA expression levels were quantified by Western Blot and Semi-quantitative reverse transcription polymerase chain reaction, respectively. Soft substrate induced faster cell swelling but slower cell recovering during chondrocyte RVD response. Stiff substrate enhanced the cytosolic Ca2+ oscillation of chondrocytes in iso-osmotic medium. Moreover, chondrocytes exhibited a completely distinctive cytosolic Ca2+ oscillation during the RVD response. Soft substrate significantly improved the Ca2+ oscillation during the cell swelling whereas stiff substrate enhanced cytosolic Ca2+ oscillation during the cell recovering. More importantly, TRPV4 channel is involved in the chondrocyte sensing substrate stiffness and RVD response by mediating Ca2+ signaling in a stiffness-dependent manner. Our work demonstrates that varying substrate stiffness induces completely different swelling and recovering processes during chondrocyte RVD response. Moreover, the TRPV4 channel is involved in chondrocyte sensing substrate stiffness and RVD response by mediating calcium signaling.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"115 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124119144","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}

{"title":"An Injectable and Tumor-Specific Responsive Hydrogel with Tissue-Adhesive and Nanomedicine-Releasing Abilities for Precise Locoregional Chemotherapy","authors":"Di Wu, Xiaoguang Shi, Fu-Lin Zhao, Sergio Tomas Fernando Chilengue, Liandong Deng, Anjie Dong, D. Kong, Weiwei Wang, Jianhua Zhang","doi":"10.2139/ssrn.3387704","DOIUrl":"https://doi.org/10.2139/ssrn.3387704","url":null,"abstract":"Locoregional chemotherapy, especially using implantable hydrogel depots to sustainably deliver chemotherapeutics at tumor site, has shown great potential for improving antitumor efficacy and reducing systemic toxicity. However, the hydrogel applications are limited by some intrinsic constraints, especially the contradiction between increasing drug penetration and accumulation in tumor and decreasing random drug diffusion into surrounding normal tissues. Herein, we report a unique \"Jekyll and Hyde\" nanoparticle-hydrogel (NP-gel) hybrid platform, which can keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative doxorubicin (DOX)-loaded NPs. Apart from tumor-specific recognition, penetration, internalization and release, NP-gel features: shear-thinning behavior for injection, tissue-adhesiveness for continuous on-site activation, and full biodegradability for safe use. Precise delivery was clearly demonstrated in both tumor-grafted and tumor-resected mice. A single peritumoral injection of DOX-loaded NP-gel exhibited a significantly higher drug accumulation in tumor for 3 weeks than in nontarget organs and thus long-term tumor remission. More importantly, significant inhibition in tumor recurrence without detectable toxicity to healthy organs was demonstrated when applied after tumor resection. The designed system displayed long-acting and precise anticancer efficacy, paving the way toward effective tumor locoregional treatment. STATEMENT OF SIGNIFICANCE: Injectable hydrogels, allowing sustained drug delivery directly at tumor site, has shown great potential for locoregional chemotherapy. However, how to achieve tumor-specific drug accumulation but meanwhile impede the random drug diffusion into surrounding normal tissues remains an insurmountable challenge, especially considering high drug concentration gradient, higher interstitial fluid pressure and denser extracellular matrix in tumor than adjacent normal tissue. Herein, a 'Jekyll and Hyde' nanoparticle-hydrogel hybrid formulation was designed to keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative DOX-loaded nanoparticles, leading to a significant tumor inhibition and antirecurrence efficiency without detectable toxicity to healthy organs, thus presenting great potential for precise locoregional chemotherapy.","PeriodicalId":216437,"journal":{"name":"ChemRN: Biomaterials (Topic)","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116293272","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}