ACS Biomaterials Science & Engineering最新文献

{"title":"Induced Extracellular Ice Nucleation Protects Cocultured Spheroid Interior and Exterior during Cryopreservation.","authors":"Yanan Gao, Akalabya Bissoyi, Qiongyu Guo, Matthew I Gibson","doi":"10.1021/acsbiomaterials.4c00958","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00958","url":null,"abstract":"<p><p>Spheroids and other 3D cellular models more accurately recapitulate physiological responses when compared to 2D models and represent potential alternatives to animal testing. The cryopreservation of spheroids remains challenging, limiting their wider use. Standard DMSO-only cryopreservation results in supercooling to low subzero temperatures, reducing viability, shedding surface cells, and perforating spheroid interiors. Here, cocultured spheroids with differentially labeled outer cell layers allow spatial evaluation of the protective effect of macromolecular ice nucleators by microscopy and histology. Extracellular nucleation is shown to reduce damage to both interior and exterior regions of the spheroids, which will support the development of \"off-the-shelf\" 3D models.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D Printed Microneedles for the Transdermal Delivery of NAD⁺ Precursor: Toward Personalization of Skin Delivery.","authors":"Masood Ali, Sarika Namjoshi, Khanh Phan, Xiaoxin Wu, Indira Prasadam, Heather A E Benson, Tushar Kumeria, Yousuf Mohammed","doi":"10.1021/acsbiomaterials.4c00905","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00905","url":null,"abstract":"<p><p>3D printing of microneedles (μNDs) for transdermal therapy has the potential to enable patient personalization based on the target disease, site of application, and dosage requirements. To convert this concept to reality, it is necessary that the 3D printing technology can deliver high resolution, an affordable cost, and large print volumes. With the introduction of benchtop 4K and 8K 3D printers, it is now possible to manufacture medical devices like μNDs at sufficient resolution and low cost. In this research, we systematically optimized the 3D printing design parameters such as resin viscosity, print angle, layer height, and curing time to generate customizable μNDs. We have also developed an innovative 3D coating microtank device to optimize the coating method. We have applied this to the development of novel μNDs to deliver an established NAD⁺ precursor molecule, nicotinamide mononucleotide (NMN). A methacrylate-based polymer photoresin (eSun resin) was diluted with methanol to adjust the resin viscosity. The 3D print layer height of 25 μm yielded a smooth surface, thus reducing edge-ridge mismatches. Printing μNDs at 90° to the print platform yielded 84.28 ± 2.158% (<i>n</i> = 5) of the input height thus increasing the tip sharpness (48.52 ± 10.43 μm, <i>n</i> = 5). The formulation containing fluorescein (model molecule), sucrose (viscosity modifier), and Tween-20 (surface tension modifier) was coated on the μNDs using the custom designed microtank setup, and the amount deposited was determined fluorescently. The dye-coated μND arrays inserted into human skin (<i>in vitro</i>) showed a fluorescence signal at a depth of 150 μm (<i>n</i> = 3) into the skin. After optimization of the 3D printing parameters and coating protocol using fluorescein, NMN was coated onto the μNDs, and its diffusion was assessed in full-thickness human skin <i>in vitro</i> using a Franz diffusion setup. Approximately 189 ± 34.5 μg (5× dipped coated μNDs) of NMN permeated through the skin and 41.2 ± 7.53 μg was left in the skin after 24 h. Multiphoton microscopy imaging of NMN-coated μND treated mouse ear skin <i>ex vivo</i> demonstrated significantly (<i>p</i> < 0.05) increased free-unbound NADPH and reduced fluorescence lifetime of NADPH, both of which are indicative of cellular metabolic rates. Our study demonstrates that low-cost benchtop 3D printers can be used to print high-fidelity μNDs with the ability to rapidly coat and release NMN which consequently caused changes in intracellular NAD⁺ levels.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PF-PEG@ASIV-EXO Hydrogel Accelerates Diabetic Wound Healing by Ferroptosis Resistance and Promoting Angiogenesis.","authors":"Wu Xiong, Xi Zhang, Jinhui Hu, Xiaoling Zou, Hongyu Huang, Wenjing Qu, Shimin Cai, Chengyu Li, Yang Wei, Xingxing Zhong, Zhaoyang Cai, Zixin Huang","doi":"10.1021/acsbiomaterials.4c00692","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00692","url":null,"abstract":"<p><p>Astragaloside IV (ASIV) promotes the proliferation of key cells, endothelial progenitor cells (EPCs), during the wound healing process, while exosomes and hydrogels are ideal drug delivery carriers. This study aims to explore the mechanism of action of the \"ROS-responsive hydrogel-engineered EPCs-targeted exosomes\" composite ASIV delivery system (PF-PEG@ASIV-EXO) in diabetic wound healing. Surface markers of EPCs and PF-PEG@ASIV-EXO were detected separately. The degradation rate of PF-PEG@ASIV-EXO was assessed after coculturing with human dermal fibroblasts (HDF), immortalized human epidermal cells (HaCAT), and human EPCs, and the biocompatibility of EPCs and PF-PEG@ASIV-EXO was evaluated through exosome release and uptake. The effects of PF-PEG@ASIV-EXO on the viability, angiogenesis, ferroptosis, and mitochondria of high-glucose-treated EPCs (HS-EPCs) were investigated. A diabetic wound rat model was established, and the effects of PF-PEG@ASIV-EXO on diabetic wounds were evaluated through HE and Masson staining, as well as levels of VWF, CD31, and ferroptosis in the skin. EPCs were successfully isolated, and PF-PEG@ASIV-EXO was successfully constructed. PF-PEG@ASIV-EXO exhibited a high degradation rate within EPCs, and both EPCs and PF-PEG@ASIV-EXO showed good biocompatibility. PF-PEG@ASIV-EXO promoted the vitality and angiogenesis of EPCs, inhibited ferroptosis, and mitigated mitochondrial damage. Following treatment with PF-PEG@ASIV-EXO, the healing of diabetic rat skin accelerated, accompanied by elevated expression of VWF and CD31, and reduced ferroptosis levels. PF-PEG@ASIV-EXO hydrogel inhibits ferroptosis, promotes angiogenesis, and thereby accelerates the healing of diabetic wounds.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Coculture Model for Assessing Competing Host Mammalian Cell and Bacterial Attachment on Zirconia versus Titanium.","authors":"Danyal A Siddiqui, Bhuvana Lakkasetter Chandrashekar, Smriti G Natarajan, Kelli L Palmer, Danieli C Rodrigues","doi":"10.1021/acsbiomaterials.4c01075","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01075","url":null,"abstract":"<p><p><i><u>Objectives:</u></i> Coculture models are limited by bacteria rapidly outcompeting host mammalian cells for nutrients <i>in vitro</i>, resulting in mammalian cell death. The goal of this study was to develop a coculture model enabling survival of mammalian cells and oral bacterial species to assess their competition for growth on dental implant materials. <i><u>Methods:</u></i> Two early colonizing oral bacterial species, <i>Streptococcus mutans</i> or <i>Actinomyces naeslundii</i>, were grown in coculture with primary human macrophages or human gingival fibroblasts for up to 7 days on tissue-culture treated polystyrene or polished titanium and zirconia disks. Chloramphenicol was supplemented in cell culture medium at bacteriostatic concentrations to maintain stable bacterial inoculum size. Planktonic and adherent bacterial growth was assessed via spot plating while mammalian cell growth and attachment were evaluated using colorimetric metabolic assay and confocal fluorescence microscopy, respectively. <i><u>Results:</u></i> Macrophages and fibroblasts proliferated in the presence of <i>S. mutans</i> and maintained viability above 70% during coculture for up to 7 days on tissue-culture treated polystyrene and polished titanium and zirconia. In contrast, both mammalian cell types exhibited decreasing proliferation and surface coverage on titanium and zirconia over time in coculture with <i>A. naeslundii</i> versus control. <i>S. mutans</i> and <i>A. naeslundii</i> were maintained within an order of magnitude of seeding inoculum sizes throughout coculture. <i><u>Significance:</u></i> Cell culture medium supplemented with antibiotics at bacteriostatic concentrations can suppress bacterial overgrowth and facilitate mammalian cell viability in coculture model systems. Within the study's limitations, oral bacteria and mammalian cell growth in coculture are comparable on polished titanium and zirconia surfaces.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Extracellular Vesicle Cargo Loading via microRNA Biogenesis Pathway Modulation.","authors":"Alex Eli Pottash, Daniel Levy, Emily H Powsner, Nicholas H Pirolli, Leo Kuo, Talia J Solomon, Raith Nowak, Jacob Wang, Stephanie M Kronstadt, Steven M Jay","doi":"10.1021/acsbiomaterials.4c00821","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00821","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are physiological vectors for the intercellular transport of a variety of molecules. Among these, small RNAs, and especially microRNAs (miRNAs), have been identified as prevalent components, and there has thus been a robust investigation of EVs for therapeutic miRNAs delivery. However, intrinsic levels of EV-associated miRNAs are generally too low to enable efficient and effective therapeutic outcomes. We hypothesized that miRNA localization to EVs could be improved by limiting competing interactions that occur throughout the miRNA biogenesis process. Using miR-146a-5p as a model, modulation of transcription, nuclear export, and enzymatic cleavage steps of miRNA biogenesis were tested for impact on EV miRNA loading. Working in HEK293T cells, various alterations in the EV biogenesis pathway were shown to impact miRNA localization to EVs. The system was then applied in induced pluripotent stem cells (iPSCs), a more promising substrate for therapeutic EV production, and EVs were separated and assessed for anti-inflammatory efficacy <i>in vitro</i> and in a murine colitis model, where the preservation of function was validated. Overall, the results highlight necessary considerations when designing a cell culture system for the devoted production of miRNA-loaded EVs.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicines with Versatile GSH-Responsive Linkers for Cancer Theranostics","authors":"Huamin Ding, Can Zhou, Tiejun Li","doi":"10.1021/acsbiomaterials.4c00897","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00897","url":null,"abstract":"Glutathione (GSH)-responsive nanomedicines have generated significant interest in biochemistry, oncology, and material sciences due to their diverse applications, including chemical and biological sensors, diagnostics, and drug delivery systems. The effectiveness of these smart GSH-responsive nanomedicines depends critically on the choice of GSH-responsive linkers. Despite their crucial role, comprehensive reviews of GSH-responsive linkers are scarce, revealing a gap in the current literature. This review addresses this gap by systematically summarizing various GSH-responsive linkers and exploring their potential applications in cancer treatment. We provide an overview of the mechanisms of action of these linkers and their bioapplications, evaluating their advantages and limitations. The insights presented aim to guide the development of advanced GSH-responsive agents for cancer diagnosis and therapy.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Cystic Fibrosis Chronic Infection Using Engineered Mucus-like Hydrogels","authors":"Courtney L. O’Brien, Sarah Spencer, Naeimeh Jafari, Andy J. Huang, Alison J. Scott, Zhenyu Cheng, Brendan M. Leung","doi":"10.1021/acsbiomaterials.4c01271","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01271","url":null,"abstract":"The airway mucus of patients with cystic fibrosis has altered properties, which create a microenvironment primed for chronic infections that are difficult to treat. These complex polymicrobial airway infections and corresponding mammalian–microbe interactions are challenging to model in vitro. Here, we report the development of mucus-like hydrogels with varied compositions and viscoelastic properties reflecting differences between healthy and cystic fibrosis airway mucus. Models of cystic fibrosis and healthy airway microenvironments were created by combining the hydrogels with relevant pathogens, human bronchial epithelial cells, and an antibiotic. Notably, pathogen antibiotic resistance was not solely dependent on the altered properties of the mucus-like hydrogels but was also influenced by culture conditions including microbe species, monomicrobial or polymicrobial culture, and the presence of epithelial cells. Additionally, the cystic fibrosis airway model showed the ability to mimic features characteristic of chronic cystic fibrosis airway infections including sustained polymicrobial growth and increased antibiotic tolerance.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Surface-Mediated Biomimetic Porous Polyether–Ether–Ketone Scaffold for Regulating Immunity and Promoting Osteogenesis","authors":"Mingyu Zhu, Liqiu Hu, Yang Liu, Pinghang Chen, Xiaofei Wang, Bin Tang, Chao Liu, Rui Zhang, Ju Fang, Fuzeng Ren","doi":"10.1021/acsbiomaterials.4c00725","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00725","url":null,"abstract":"The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether–ether–ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells’ adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin β1-specific cell-matrix binding and the activation of Ca²⁺ receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration <i>in vivo</i>. This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Thermomechanical Processing Induced Retained Strain on In Vitro, In Vivo Biodegradation Response and Cytocompatibility of Mg Alloy","authors":"Darothi Bairagi, Santanu Mandal, Samsamul Hoque, Debaki Ghosh, Samit Kumar Nandi, Samiran Mondal, Mangal Roy, Manas Paliwal, Sumantra Mandal","doi":"10.1021/acsbiomaterials.4c00823","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00823","url":null,"abstract":"The implications of retained strain on <i>in vitro</i> and <i>in vivo</i> degradation behavior as well as cytocompatibility of the Mg–4Zn–0.5Ca–0.8Mn alloy is comprehensively studied. The retained strain is induced in homogenized specimens by hard-plate hot forging (HPHF) at a temperature (523 K) lower than the recrystallization temperature of the alloy. The retained strain generated during deformation process deteriorated the corrosion response of the deformed alloy as compared to its homogenized counterpart. The strained area of deformed specimen with high dislocation density promoted defect generation (oxygen vacancies) in the film and facilitated preferential migration of ions, consequently leading to formation of a nonuniform product film with low protectiveness. In addition to strain magnitude, the distribution of retained strain also influenced the product film properties in the deformed specimens. An even distribution of retained strain improved the uniformity of the product film to certain extent by providing greater film coverage, resulting in higher film resistance. After 24 h of immersion, the protectiveness of the film was further improved in this specimen due to annihilation of defects through homogeneous ionic migration, which led to the development of a uniform and stable film that restricted further ionic diffusion. The dissolution of Zn(OH)₂ into Zn²⁺ ions was promoted at lower pH, resulting in enhanced antimicrobial activity in the specimen with the lowest degradation. Besides, the specimen with stable product film not only minimized the rate of further degradation but also served as an interface for new bone growth, as evident from <i>in vivo</i> studies.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Initial Secondary Structure on Conformation and Mechanical Properties of Spider Silk Protein Gels","authors":"Takanori Higashi, Hideyasu Okamura, Takehiro K. Sato, Takashi Morinaga, Ryo Satoh, Yu Suzuki","doi":"10.1021/acsbiomaterials.4c00809","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00809","url":null,"abstract":"Recombinant spider silk protein (RSP) is a promising biomaterial for developing high-performance materials independent of fossil fuels. In this study, we investigated the influence of the initial secondary structure of RSPs on the properties of RSP-based hydrogels. By altering the initial structure of RSP to β-sheets (β-RSP), α-helices (α-RSP), and random coils (rc-RSP) through solvent treatment, we compared the structures and mechanical properties of the resulting gels. Solid-state NMR revealed a β-sheet-rich structure in all gels, with the α-RSP gel exhibiting significantly higher strength and Young’s modulus compared to the rc-RSP gel. X-ray diffraction revealed that the α-RSP gel had a unique crystalline structure, distinguishing it from the β-RSP and rc-RSP gels. The different initial secondary structures possibly lead to variations in the crystalline and network structures of the molecular chains within the gels, explaining the superior mechanical properties observed in the α-RSP gels.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}