Acta Biomaterialia最新文献

{"title":"Quantifying the microstructural and biomechanical changes in the porcine ventricles during growth and remodelling","authors":"Faizan Ahmad ,&nbsp;Shwe Soe ,&nbsp;Julie Albon ,&nbsp;Rachel Errington ,&nbsp;Peter Theobald","doi":"10.1016/j.actbio.2023.09.044","DOIUrl":"10.1016/j.actbio.2023.09.044","url":null,"abstract":"<div><p>Cardiac tissue growth and remodelling (G &amp; R) occur in response to the changing physiological demands of the heart after birth. The early shift to pulmonary circulation produces an immediate increase in ventricular workload, causing microstructural and biomechanical changes that serve to maintain overall physiological homoeostasis. Such cardiac G &amp; R continues throughout life. Quantifying the tissue's mechanical and microstructural changes because of G &amp; R is of increasing interest, dovetailing with the emerging fields of personalised and precision solutions. This study aimed to determine equibiaxial, and non-equibiaxial extension, stress-relaxation, and the underlying microstructure of the passive porcine ventricles tissue at four time points spanning from neonatal to adulthood. The three-dimensional microstructure was investigated via two-photon excited fluorescence and second-harmonic generation microscopy on optically cleared tissues, describing the 3D orientation, rotation and dispersion of the cardiomyocytes and collagen fibrils. The results revealed that during biomechanical testing, myocardial ventricular tissue possessed non-linear, anisotropic, and viscoelastic behaviour. An increase in stiffness and viscoelasticity was noted for the left and right ventricular free walls from neonatal to adulthood. Microstructural analyses revealed concomitant increases in cardiomyocyte rotation and dispersion. This study provides baseline data, describing the biomechanical and microstructural changes in the left and right ventricular myocardial tissue during G &amp; R, which should prove valuable to researchers in developing age-specific, constitutive models for more accurate computational simulations.</p></div><div><h3>Statement of significance</h3><p>There is a dearth of experimental data describing the growth and remodelling of left and right ventricular tissue. The published literature is fragmented, with data reported via different experimental techniques using tissues harvested from a variety of animals, with different gender and ages. This prevents developing a continuum of data spanning birth to death, so limiting the potential that can be leveraged to aid computational modelling and simulations. In this study, equibiaxial, non-equibiaxial, and stress–relaxation data are presented, describing directional-dependent material responses. The biomechanical data is consolidated with equivalent microstructural data, an important element for the development of future material models. Combined, these data describe microstructural and biomechanical changes in the ventricles, spanning G &amp;R from neonatal to adulthood.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"171 ","pages":"Pages 166-192"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib delivery using a Gd/Fe bimetallic MOF: Enhancing antitumor immunity following microwave-based thermal therapy","authors":"Qiaozheng Wang ,&nbsp;Xiaowen Zhu ,&nbsp;Xianwei Meng ,&nbsp;Hongshan Zhong","doi":"10.1016/j.actbio.2023.09.052","DOIUrl":"10.1016/j.actbio.2023.09.052","url":null,"abstract":"<div><p>Microwave (MW) thermal therapy has been developed as an effective clinical strategy that can achieve pronounced antitumor activity and also has the potential to trigger antitumor immunity. However, patients generally face high rates of tumor recurrence following MW treatment, limiting the long-term benefits of such treatment. The combination of MW treatment and immunomodulatory strategies may represent a promising means of reprogramming the immunosuppressive tumor microenvironment (TME) in a manner conducive to lower recurrence rates. In this study, a Lenvatinib-loaded Gd/Fe metal-organic framework (Gd/FeMOF) was designed as a promising approach to enhancing such antitumor immunity. MW-enhanced dynamic Gd/FeMOF sensitization can facilitate high levels of reactive oxygen species production under MW irradiation, resulting in stronger immunogenic tumor cell death. In parallel, the Lenvatinib released from Gd/FeMOF preparations can serve as an immune adjuvant that suppresses programmed death ligand 1 (PD-L1) expression and drives the reprogramming of the immunosuppressive TME. The Gd and Fe present within this MOF preparation also imbue it with magnetic resonance imaging capabilities. Importantly, <em>in vivo</em> animal model experiments confirmed the ability of GdFeMOF treatment to significantly enhance antitumor immunity while protecting against recurrence. Accordingly, this study offers a foundation for promising strategies aimed at the integrated diagnosis and durable treatment of cancer.</p></div><div><h3>Statement of Significance</h3><p>High rates of tumor recurrence following MW thermal therapy limit the long-term benefits of such treatment. We found that the administration of Lenvatinib-loaded Gd/FeMOF nanoparticles significantly reduced tumor recurrence after MW thermal therapy. Under MW irradiation, the Gd/FeMOF nanoparticles were found to augment the immune response due to facilitation of the process of immunogenic cell death. In addition, the released Lenvatinib could act as an immune adjuvant to downregulate the expression of PD-L1 and reprogram the immunosuppressive state of the tumor microenvironment, thus further enhancing the immune response. This is significant because MW-induced immune responses are relatively weak and usually fail to effectively prevent tumor recurrence. The combination of MW treatment with an immunomodulatory strategy may solve this problem.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"172 ","pages":"Pages 382-394"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1742706123006001/pdfft?md5=91d778ff0465e5e3881d04ac502f5520&pid=1-s2.0-S1742706123006001-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy","authors":"Yinghui Xu ,&nbsp;Jiayi Bian ,&nbsp;Xin Liu ,&nbsp;Zhengzheng Qian ,&nbsp;Minghao Sun ,&nbsp;Cheng Zhang ,&nbsp;Ruiyang Pan ,&nbsp;Qitong Li ,&nbsp;Changrui Sun ,&nbsp;Bin Lin ,&nbsp;Kun Peng ,&nbsp;Nan Lu ,&nbsp;Xikuang Yao ,&nbsp;Wenpei Fan","doi":"10.1016/j.actbio.2023.10.001","DOIUrl":"10.1016/j.actbio.2023.10.001","url":null,"abstract":"<div><p>Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H₂O₂ at the tumor site. More importantly, the self-supplied peroxide hydrogen (H₂O₂) can convert ABTS (2,2′-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe²⁺ arising from the reduction of Fe³⁺ by overexpressed GSH reacts with H₂O₂ to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies.</p></div><div><h3>Statement of significance</h3><p>Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H₂O₂ self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H₂O₂. The self-supplied H₂O₂ initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"172 ","pages":"Pages 441-453"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1742706123006013/pdfft?md5=99d76e289a4ef9a0d18b96c85314091b&pid=1-s2.0-S1742706123006013-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untangling the mechanisms of pulmonary arterial hypertension-induced right ventricular stiffening in a large animal model","authors":"Sotirios Kakaletsis ,&nbsp;Marcin Malinowski ,&nbsp;J. Caleb Snider ,&nbsp;Mrudang Mathur ,&nbsp;Gabriella P. Sugerman ,&nbsp;Jeffrey J. Luci ,&nbsp;Colton J. Kostelnik ,&nbsp;Tomasz Jazwiec ,&nbsp;Matthew R. Bersi ,&nbsp;Tomasz A. Timek ,&nbsp;Manuel K. Rausch","doi":"10.1016/j.actbio.2023.09.043","DOIUrl":"10.1016/j.actbio.2023.09.043","url":null,"abstract":"<div><p>Pulmonary hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) stiffening; thus, impeding diastolic filling. Multiple mechanisms may contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model to untangle these mechanisms. Thus, we induced pulmonary arterial hypertension (PAH) in sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. Finally, we used finite element modeling to disentangle the relative importance of each stiffening mechanism. We found that the RVs of PAH animals thickened most at the base and the free wall and that PAH induced excessive collagen synthesis, increased cardiomyocyte cross-sectional area, and led to microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with collagen synthesis. Finally, our computational models predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Thus, myocardial stiffening may be the most important predictor for PAH progression. Given the correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for estimating myocardial stiffness and predicting PAH outcomes.</p></div><div><h3>Statement of significance</h3><p>Ventricular stiffening is a significant contributor to pulmonary hypertension-induced right heart failure. However, the mechanisms that lead to ventricular stiffening are not fully understood. The novelty of our work lies in answering this question through the use of a large animal model in combination with spatially- and directionally sensitive experimental techniques. We find that myocardial stiffness is the primary mechanism that leads to ventricular stiffening. Clinically, this knowledge may be used to improve diagnostic, prognostic, and therapeutic strategies for patients with pulmonary hypertension.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"171 ","pages":"Pages 155-165"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual scaffold delivery of miR-210 mimic and miR-16 inhibitor enhances angiogenesis and osteogenesis to accelerate bone healing","authors":"Irene Mencía Castaño ,&nbsp;Rosanne M. Raftery ,&nbsp;Gang Chen ,&nbsp;Brenton Cavanagh ,&nbsp;Brian Quinn ,&nbsp;Garry P. Duffy ,&nbsp;Caroline M. Curtin ,&nbsp;Fergal J. O'Brien","doi":"10.1016/j.actbio.2023.09.049","DOIUrl":"10.1016/j.actbio.2023.09.049","url":null,"abstract":"<div><p>Angiogenesis is critical for successful bone repair, and interestingly, miR-210 and miR-16 possess counter-active targets involved in both angiogenesis and osteogenesis: miR-210 acts as an activator by silencing EFNA3 &amp; AcvR1b, while miR-16 inhibits both pathways by silencing VEGF &amp; Smad5. It was thus hypothesized that dual delivery of both a miR-210 mimic and a miR-16 inhibitor from a collagen-nanohydroxyapatite scaffold system may hold significant potential for bone repair. Therefore, this systems potential to rapidly accelerate bone repair by directing enhanced angiogenic-osteogenic coupling in host cells in a rat calvarial defect model at a very early 4 week timepoint was assessed. <em>In vitro</em>, the treatment significantly enhanced angiogenic-osteogenic coupling of human mesenchymal stem cells, with enhanced calcium deposition after just 10 days in 2D and 14 days on scaffolds. <em>In vivo</em>, these dual-miRNA loaded scaffolds showed more than double bone volume and vessel recruitment increased 2.3 fold over the miRNA-free scaffolds. Overall, this study demonstrates the successful development of a dual-miRNA mimic/inhibitor scaffold for enhanced <em>in vivo</em> bone repair for the first time, and the possibility of extending this ‘off-the-shelf’ platform system to applications beyond bone offers immense potential to impact a myriad of other tissue engineering areas.</p></div><div><h3>Statement of significance</h3><p>miRNAs have potential as a new class of bone healing therapeutics as they can enhance the regenerative capacity of bone-forming cells. However, angiogenic-osteogenic coupling is critical for successful bone repair. Therefore, this study harnesses the delivery of miR-210, known to be an activator of both angiogenesis and osteogenesis, and miR-16 inhibitor, as miR-16 is known to inhibit both pathways, from a collagen-nanohydroxyapatite scaffold system to rapidly enhance osteogenesis <em>in vitro</em> and bone repair <em>in vivo</em> in a rat calvarial defect model. Overall, it describes the successful development of the first dual-miRNA mimic/inhibitor scaffold for enhanced <em>in vivo</em> bone repair. This ‘off-the-shelf’ platform system offers immense potential to extend beyond bone applications and impact a myriad of other tissue engineering areas.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"172 ","pages":"Pages 480-493"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1742706123005974/pdfft?md5=9781b126e5ce36c919a8dba2336af7a3&pid=1-s2.0-S1742706123005974-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue behaviour of load-bearing polymeric bone scaffolds: A review","authors":"Hamed Bakhtiari ,&nbsp;Alireza Nouri ,&nbsp;Mehrdad Khakbiz ,&nbsp;Majid Tolouei-Rad","doi":"10.1016/j.actbio.2023.09.048","DOIUrl":"10.1016/j.actbio.2023.09.048","url":null,"abstract":"<div><p>Bone scaffolds play a crucial role in bone tissue engineering by providing mechanical support for the growth of new tissue while enduring static and fatigue loads. Although polymers possess favourable characteristics such as adjustable degradation rate, tissue-compatible stiffness, ease of fabrication, and low toxicity, their relatively low mechanical strength has limited their use in load-bearing applications. While numerous studies have focused on assessing the static strength of polymeric scaffolds, little research has been conducted on their fatigue properties. The current review presents a comprehensive study on the fatigue behaviour of polymeric bone scaffolds. The fatigue failure in polymeric scaffolds is discussed and the impact of material properties, topological features, loading conditions, and environmental factors are also examined. The present review also provides insight into the fatigue damage evolution within polymeric scaffolds, drawing comparisons to the behaviour observed in natural bone. Additionally, the effect of polymer microstructure, incorporating reinforcing materials, the introduction of topological features, and hydrodynamic/corrosive impact of body fluids in the fatigue life of scaffolds are discussed. Understanding these parameters is crucial for enhancing the fatigue resistance of polymeric scaffolds and holds promise for expanding their application in clinical settings as structural biomaterials.</p></div><div><h3>Statement of Significance</h3><p>Polymers have promising advantages for bone tissue engineering, including adjustable degradation rates, compatibility with native bone stiffness, ease of fabrication, and low toxicity. However, their limited mechanical strength has hindered their use in load-bearing scaffolds for clinical applications. While prior studies have addressed static behaviour of polymeric scaffolds, a comprehensive review of their fatigue performance is lacking. This review explores this gap, addressing fatigue characteristics, failure mechanisms, and the influence of parameters like material properties, topological features, loading conditions, and environmental factors. It also examines microstructure, reinforcement materials, pore architectures, body fluids, and tissue ingrowth effects on fatigue behaviour. A significant emphasis is placed on understanding fatigue damage progression in polymeric scaffolds, comparing it to natural bone behaviour.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"172 ","pages":"Pages 16-37"},"PeriodicalIF":9.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1742706123005962/pdfft?md5=4602bfc158ecade282999a9cb09d2f66&pid=1-s2.0-S1742706123005962-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrostatic pressure under hypoxia facilitates fabrication of tissue-engineered vascular grafts derived from human vascular smooth muscle cells in vitro","authors":"Tomoyuki Kojima ,&nbsp;Takashi Nakamura ,&nbsp;Junichi Saito ,&nbsp;Yuko Hidaka ,&nbsp;Taisuke Akimoto ,&nbsp;Hana Inoue ,&nbsp;Christian Nanga Chick ,&nbsp;Toyonobu Usuki ,&nbsp;Makoto Kaneko ,&nbsp;Etsuko Miyagi ,&nbsp;Yoshihiro Ishikawa ,&nbsp;Utako Yokoyama","doi":"10.1016/j.actbio.2023.09.041","DOIUrl":"10.1016/j.actbio.2023.09.041","url":null,"abstract":"<div><p>Biologically compatible vascular grafts are urgently required. The scaffoldless multi-layered vascular wall is considered to offer theoretical advantages, such as facilitating cells to form cell-cell and cell-matrix junctions and natural extracellular matrix networks. Simple methods are desired for fabricating physiological scaffoldless tissue-engineered vascular grafts. Here, we showed that periodic hydrostatic pressurization under hypoxia (HP/HYP) facilitated the fabrication of multi-layered tunica media entirely from human vascular smooth muscle cells. Compared with normoxic atmospheric pressure, HP/HYP increased expression of N-myc downstream-regulated 1 (NDRG1) and the collagen-cross-linking enzyme lysyl oxidase in human umbilical artery smooth muscle cells. HP/HYP increased N-cadherin-mediated cell-cell adhesion via NDRG1, cell-matrix interaction (i.e., clustering of integrin α5β1 and fibronectin), and collagen fibrils. We then fabricated vascular grafts using HP/HYP during repeated cell seeding and obtained 10-layered smooth muscle grafts with tensile rupture strength of 0.218–0.396 MPa within 5 weeks. Implanted grafts into the rat aorta were endothelialized after 1 week and patent after 5 months, at which time most implanted cells had been replaced by recipient-derived cells. These results suggest that HP/HYP enables fabrication of scaffoldless human vascular mimetics that have a spatial arrangement of cells and matrices, providing potential clinical applications for cardiovascular diseases.</p></div><div><h3>Statement of significance</h3><p>Tissue-engineered vascular grafts (TEVGs) are theoretically more biocompatible than prosthetic materials in terms of mechanical properties and recipient cell-mediated tissue reconstruction. Although some promising results have been shown, TEVG fabrication processes are complex, and the ideal method is still desired. We focused on the environment in which the vessels develop in utero and found that mechanical loading combined with hypoxia facilitated formation of cell-cell and cell-matrix junctions and natural extracellular matrix networks in vitro, which resulted in the fabrication of multi-layered tunica media entirely from human umbilical artery smooth muscle cells. These scaffoldless TEVGs, produced using a simple process, were implantable and have potential clinical applications for cardiovascular diseases.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"171 ","pages":"Pages 209-222"},"PeriodicalIF":9.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive and chemically defined hydrogels with tunable stiffness guide cerebral organoid formation and modulate multi-omics plasticity in cerebral organoids","authors":"Melis Isik ,&nbsp;Babatunde O. Okesola ,&nbsp;Cemil Can Eylem ,&nbsp;Engin Kocak ,&nbsp;Emirhan Nemutlu ,&nbsp;Matteo D'Este ,&nbsp;Alvaro Mata ,&nbsp;Burak Derkus","doi":"10.1016/j.actbio.2023.09.040","DOIUrl":"10.1016/j.actbio.2023.09.040","url":null,"abstract":"<div><p>Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactivity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69 kPa to 2.24 kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolecular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM-like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels containing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research.</p></div><div><h3>Statement of significance</h3><p>Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic matrices are chemically defined and animal-free compared to current gold standard matrices such as Matrigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"171 ","pages":"Pages 223-238"},"PeriodicalIF":9.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A synergistic strategy of dual-crosslinking and loading intelligent nanogels for enhancing anti-coagulation, pro-endothelialization and anti-calcification properties in bioprosthetic heart valves","authors":"Mengyue Hu ,&nbsp;Shubin Shi ,&nbsp;Xu Peng ,&nbsp;Xinyun Pu ,&nbsp;Xixun Yu","doi":"10.1016/j.actbio.2023.09.045","DOIUrl":"10.1016/j.actbio.2023.09.045","url":null,"abstract":"<div><p>Currently, glutaraldehyde (GA)-crosslinked bioprosthetic heart valves (BHVs) still do not guarantee good biocompatibility and long-term effective durability for clinical application due to their subacute thrombus, inflammation, calcification, tearing and limited durability. In this study, double-modified xanthan gum (oxidized/vinylated xanthan gum (O₂CXG)) was acquired from xanthan gum for subsequent double crosslinking and modification platform construction. Sulfonic acid groups with anticoagulant properties were also introduced through the free radical polymerization of vinyl sulfonate (VS) and vinyl on O₂CXG. Taking advantage of the drug-loading function of xanthan gum, the treated pericardium was further loaded with inflammation-triggered dual drug-loaded nanogel (heparin (Hep) and atorvastatin (Ator)). Mechanical properties of O₂CXG-crosslinked porcine pericardium (O₂CXG-PP) were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Due to the presence of sulfonic acid groups as well as the dual drug release from nanogels under the stimulation of H₂O₂, the hemocompatibility, anti-inflammatory, pro-endothelialization and anti-calcification properties of the crosslinked pericardium modified with nanogels loaded with Hep and Ator (O₂CXG+VS+(Hep+Ator) nanogel-PP) was significantly better than that of GA-crosslinked PP (GA-PP). The collaborative strategy of double crosslinking and sequential release of anticoagulant/endothelium-promoting drugs triggered by inflammation could effectively meet the requirement of enhanced multiple performance and long-term durability of bioprosthetic heart valves and provide a valuable pattern for multi-functionalization of blood contacting materials.</p></div><div><h3>Statement of significance</h3><p>Currently, glutaraldehyde-crosslinked bioprosthetic heart valves (BHVs) are subject to subacute thrombus, inflammation, calcification and tearing, which would not guarantee good biocompatibility and long-term effective durability. We developed a cooperative strategy of double crosslinking and surface modification in which double-modified xanthan gum plays a cornerstone. The mechanical properties of this BHV were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Inflammation-triggered combination delivery of heparin and atorvastatin has been demonstrated to enhance anticoagulation, anti-inflammatory and pro-endothelialization of BHVs by utilizing local inflammatory response. The collaborative strategy could effectively meet the requirement of enhanced multiple performance and long-term durability of BHVs and provide a valuable pattern for the multi-functionalization of blood-contacting materials.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"171 ","pages":"Pages 466-481"},"PeriodicalIF":9.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions","authors":"Duy T. Nguyen ,&nbsp;Ruixuan Liu ,&nbsp;Elizabeth Ogando-Rivas ,&nbsp;Alfonso Pepe ,&nbsp;Diego Pedro ,&nbsp;Sadeem Qdaisat ,&nbsp;Nhi Tran Yen Nguyen ,&nbsp;Julia M. Lavrador ,&nbsp;Griffin R. Golde ,&nbsp;Ryan A. Smolchek ,&nbsp;John Ligon ,&nbsp;Linchun Jin ,&nbsp;Haipeng Tao ,&nbsp;Alex Webber ,&nbsp;Simon Phillpot ,&nbsp;Duane A. Mitchell ,&nbsp;Elias J. Sayour ,&nbsp;Jianping Huang ,&nbsp;Paul Castillo ,&nbsp;W. Gregory Sawyer","doi":"10.1016/j.actbio.2023.09.042","DOIUrl":"10.1016/j.actbio.2023.09.042","url":null,"abstract":"<div><p>Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with <em>in situ</em> imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.</p></div><div><h3>Statement of significance</h3><p>The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative <em>in vitro</em> three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"172 ","pages":"Pages 466-479"},"PeriodicalIF":9.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1742706123005925/pdfft?md5=883a934963c6c6d8057778f47866224d&pid=1-s2.0-S1742706123005925-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}