ACS Biomaterials Science & Engineering最新文献

{"title":"Piezo1 Mediates Glycolysis-Boosted Pancreatic Ductal Adenocarcinoma Chemoresistance within a Biomimetic Three-Dimensional Matrix Stiffness.","authors":"Haopeng Pan, Xue Zhang, Shajun Zhu, Biwen Zhu, Di Wu, Jiashuai Yan, Xiaoqi Guan, Yan Huang, Yahong Zhao, Yumin Yang, Yibing Guo","doi":"10.1021/acsbiomaterials.4c01319","DOIUrl":"10.1021/acsbiomaterials.4c01319","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a very low 5-year survival rate, which is partially attributed to chemoresistance. Although the regulation of chemoresistance through biochemical signaling is well-documented, the influence of three-dimensional (3D) matrix stiffness is poorly understood. In this study, gelatin methacrylate (GelMA) hydrogels were reconstructed with stiffnesses spanning the range from normal to cancerous PDAC tissues, which are termed as the soft group and stiff group. The PDAC cell lines (Mia-PaCa2 and CFPAC-1) encapsulated in the stiff group displayed a chemoresistance phenotype and were prominent against gemcitabine. RNA-sequencing and bioinformatics analysis indicated that glycolysis was apparently enriched in the stiff group <i>versus</i> the soft group, which was also validated through assays of glucose uptake, lactate production, and the expression of GLUT2, HK2, and LDHA. A rescue assay with 2-deoxy-d-glucose and <i>N</i>-acetylcysteine demonstrated that glycolysis is involved in chemoresistance. Furthermore, the expression of Piezo1 and the content of Ca²⁺ were elevated in the stiff group. The addition of Yoda1 (Piezo1 agonist) in the soft group promoted glycolysis, whereas in the stiff group, treatment with GsMTx4 (Piezo1 inhibitor) inhibited glycolysis, which showcased that Piezo1 participated in 3D matrix stiffness-induced glycolysis. Taken together, Piezo1-mediated glycolysis was involved in PDAC chemoresistance triggered by the 3D matrix stiffness. Our study sheds light on the mechanism underlying chemoresistance in PDAC from the perspective of 3D mechanical cues.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7632-7646"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666384","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":"Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.","authors":"Quinn T Ehlen, Joseph P Costello, Nicholas A Mirsky, Blaire V Slavin, Marcelo Parra, Albert Ptashnik, Vasudev Vivekanand Nayak, Paulo G Coelho, Lukasz Witek","doi":"10.1021/acsbiomaterials.4c01279","DOIUrl":"10.1021/acsbiomaterials.4c01279","url":null,"abstract":"<p><p>Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7314-7336"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Stiffness Measurement of Hepatic Steatosis Model Liver Organoid by Fluorescence Imaging-Assisted Probe Indentation.","authors":"Dae-Seop Shin, Myung Jin Son, Myungae Bae, Hyunwoo Kim","doi":"10.1021/acsbiomaterials.4c01242","DOIUrl":"10.1021/acsbiomaterials.4c01242","url":null,"abstract":"<p><p>Mechanical stiffness of liver organoid is a key indicator for the progress of hepatic steatosis. Probe indentation is a noninvasive methodology to measure Young's modulus (YM); however, the inhomogeneous nature of the liver organoid induces measurement uncertainty requiring a large number of indentations covering a wide scanning area. Here, we demonstrate that lipid-stained fluorescence imaging-assisted probe indentation significantly reduces the number of measurements by specifying the highly lipid-induced area. Lipid-stained hepatic steatosis model liver organoid shows broad fluorescence distributions that are spatially correlated with a decreased YM on a lipid-filled region with bright fluorescence compared with that measured on a blank region with dark fluorescence. The organoid viability remained robust even after exposure to an ambient condition up to 6 h, showing that probe indentations can be noninvasive methods for liver organoid stiffness measurements.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7386-7393"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674431","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":"Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.","authors":"Yunyang Li, Jingwen Wu, Peilin Ye, Yilin Cai, Mingfei Shao, Tong Zhang, Yanchuan Guo, Sujuan Zeng, Janak L Pathak","doi":"10.1021/acsbiomaterials.4c01764","DOIUrl":"10.1021/acsbiomaterials.4c01764","url":null,"abstract":"<p><p>Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7372-7385"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566440","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":"Surface Engineered Osteoblast-Extracellular Vesicles Serve as an Efficient Carrier for Drug and Small RNA to Actively Target Osteosarcoma.","authors":"Sasmita Samal, Gyanendra Prasad Panda, Sharmishtha Shyamal, Kapilash Das, Mamoni Dash","doi":"10.1021/acsbiomaterials.4c00952","DOIUrl":"10.1021/acsbiomaterials.4c00952","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a rare malignant tumor that affects soft tissue and has high rates of lung metastasis and mortality. The primary treatments for OS include preoperative chemotherapy, surgical resection of the lesion, and postoperative chemotherapy. However, OS chemotherapy presents critical challenges related to treatment toxicity and multiple drug resistance. To address these challenges, nanotechnology has developed nanosystems that release drugs directly to OS cells, reducing the drug's toxicity. Extracellular vesicles (EVs) are nanosized lipid-bilayer bound vesicles that act as cell-derived vehicles and drug delivery systems for several cancers. This study aims to utilize EVs for OS management by co-delivering Hdac1 siRNA and zoledronic acid (zol). The EVs' surface is modified with folic acid (FA) and their targeting ability is compared to that of native EVs. The results showed that the EVs' targeting ability depends on the parent cell source, and FA conjugation further enhanced it. Furthermore, EVs were used as the carrier for co-loading drug (zol) and small RNA (Hdac-1). This approach of using surface engineered EVs as carriers for cargo loading and delivery can be a promising strategy for osteosarcoma management.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7466-7481"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986731","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 Hydroxyapatite Nanowires on Formation and Bioactivity of Osteoblastic Cell Spheroid.","authors":"Hanjing Li, Hongwei Chen, Chunyuan Du, Yucheng Liu, Li Wan, Fanrong Ai, Kui Zhou","doi":"10.1021/acsbiomaterials.4c01159","DOIUrl":"10.1021/acsbiomaterials.4c01159","url":null,"abstract":"<p><p>Compared with traditional high-density cell spheroids, which are more prone to core necrosis, nanowires effectively improve the biological activity of core cells in spheroids, emanating more innovations for optimizing the internal cell survival environment and providing differentiation signals. In this study, hydroxyapatite nanowires (HAW), which provide numerous material exchange channels for internal cells by interpenetrating into cell spheroids, were added to osteoblast precursor (MC3T3-E1) cell spheroids. HAW, synthesized using the hydrothermal method, was used as a regulatory material to prepare uniformly sized 3D composite spheroids with good biological activity. Subsequently, material characterization and biocompatibility tests were performed on HAW, and the biological activity and osteogenic differentiation ability of the cell spheroids were tested. Notably, in 2D coculture, HAW displayed a certain attraction to MC3T3-E1 cells and promoted cell aggregation toward it. The content of HAW determined whether composite cell spheroids can form aggregated spherical structures, and incorporation of HAW alleviated core necrosis and enhanced the osteogenic phenotype. In summary, these findings indicate that the prepared HAW-bone cell composite spheroids can potentially be used as building blocks for the construction of large high-density biomimetic tissues and organoids using 3D bioprinting technology.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7413-7428"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453188","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":"DNA Aptamers That Bind to Alginate Hydrogels.","authors":"Ali Parvez, Dana A Baum","doi":"10.1021/acsbiomaterials.4c01436","DOIUrl":"10.1021/acsbiomaterials.4c01436","url":null,"abstract":"<p><p>Hydrogels have become common in wound treatment because they form very stable and biocompatible environments that promote healing. However, due to the highly porous hydrogel structure, any therapeutic added to these gels tends to diffuse quickly and impact delivery to the target site. Aptamers are short, single-stranded DNA or RNA sequences that bind specifically to a target, so aptamers that bind to hydrogels could serve as tags for therapeutics to prevent rapid diffusion and allow for extended delivery. An in vitro selection approach was developed to identify DNA aptamers for alginate hydrogels. Two DNA aptamers were shown to bind hydrogels ranging from 0.5 to 2% alginate and could be either encapsulated during gelation or introduced to preformed gels. Both aptamers also showed specificity for binding to alginate compared to agarose. To demonstrate the functional aspect of the aptamers as tethers for other biomolecules, both aptamers were conjugated to BSA. Aptamer-conjugated BSA was retained longer in the hydrogel during week-long diffusion studies both when encapsulated or introduced to preformed gels, which adds flexibility to how these aptamers can be deployed in a clinical setting.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7507-7515"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680230","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":"Mechanical and Physical Characterization of a Biphasic 3D Printed Silk-Infilled Scaffold for Osteochondral Tissue Engineering.","authors":"T Braxton, K Lim, C Alcala-Orozco, H Joukhdar, J Rnjak-Kovacina, N Iqbal, T Woodfield, D Wood, C Brockett, X B Yang","doi":"10.1021/acsbiomaterials.4c01865","DOIUrl":"10.1021/acsbiomaterials.4c01865","url":null,"abstract":"<p><p>Osteochondral tissue damage is a serious concern, with even minor cartilage damage dramatically increasing an individual's risk of osteoarthritis. Therefore, there is a need for an early intervention for osteochondral tissue regeneration. 3D printing is an exciting method for developing novel scaffolds, especially for creating biological scaffolds for osteochondral tissue engineering. However, many 3D printing techniques rely on creating a lattice structure, which often demonstrates poor cell bridging between filaments due to its large pore size, reducing regenerative speed and capacity. To tackle this issue, a novel biphasic scaffold was developed by a combination of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene-terephthalate) (PEGT/PBT) lattice infilled with a porous silk scaffold (derived from <i>Bombyx mori</i> silk fibroin) to make up a bone phase, which continued to a seamless silk top layer, representing a cartilage phase. Compression testing showed scaffolds had Young's modulus, ultimate compressive strength, and fatigue resistance that would allow for their theoretical survival during implantation and joint articulation without stress-shielding mechanosensitive cells. Fluorescent microscopy showed biphasic scaffolds could support the attachment and spreading of human mesenchymal stem cells from bone marrow (hMSC-BM). These promising results highlight the potential utilization of this novel scaffold for osteochondral tissue regeneration as well as highlighting the potential of infilling silk materials within 3D printed scaffolds to further increase their versatility.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7606-7618"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.","authors":"Payton J Martinez, Jane J Song, Jair I Castillo, John DeSisto, Kang-Ho Song, Adam L Green, Mark Borden","doi":"10.1021/acsbiomaterials.4c00777","DOIUrl":"10.1021/acsbiomaterials.4c00777","url":null,"abstract":"<p><p>Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 μm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 μm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor <i>in vivo</i> stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7451-7465"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574779","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":"The Photocleavable Protein PhoCl-Based Dynamic Hydrogels.","authors":"Jingqi Lei, Hongbin Li","doi":"10.1021/acsbiomaterials.4c01584","DOIUrl":"10.1021/acsbiomaterials.4c01584","url":null,"abstract":"<p><p>Dynamic protein hydrogels have attracted increasing attention owing to their tunable physiochemical and mechanical properties, customized functionality, and biocompatibility. Among the different types of dynamic hydrogels, photoresponsive hydrogels are of particular interest. Here, we report the engineering of a photoresponsive protein hydrogel by using the photocleavable protein PhoCl. We employed the well-developed SpyTag and SpyCatcher chemistry to engineer PhoCl-containing covalently cross-linked hydrogels. In the hydrogel network, PhoCl, which can be cleaved into two fragments upon violet irradiation, is employed as a dynamic structural motif to regulate the cross-linking density of the hydrogel network. The resultant PhoCl-containing hydrogels showed photoresponsive viscoelastic properties. Upon violet irradiation, the PhoCl hydrogels soften, leading to an irreversible reduction in the storage moduli. However, no gel-sol transition was observed. Leveraging this light-induced stiffness change, we employed this hydrogel as a cell culture substrate to investigate the mechanobiological response of NIH-3T3 fibroblast cells. Our results showed that 3T3 cells can change their morphologies in response to the stiffness change of the PhoCl hydrogel substrate dynamically, rendering PhoCl-based hydrogels a useful substrate for other mechanobiological studies.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7404-7412"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638002","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}