Acta Biomaterialia最新文献

{"title":"Understanding the hierarchical structure of collagen fibers of the human periodontal ligament: Implications for biomechanical characteristics","authors":"Mao Liu ,&nbsp;Bin Wu ,&nbsp;Fan Yang ,&nbsp;Di Jiang ,&nbsp;Iman Izadikhah ,&nbsp;Yingyu Chen ,&nbsp;Na Li ,&nbsp;Bin Yan","doi":"10.1016/j.actbio.2024.09.016","DOIUrl":"10.1016/j.actbio.2024.09.016","url":null,"abstract":"<div><div>The periodontal ligament (PDL) is a unique fibrous connective tissue that regulates periodontal homeostasis mechanisms. Its biomechanical properties primarily reside in the hierarchical and non-uniform collagenous network. This study aimed to investigate the region-specific structure and composition of collagen fibers in the PDL at various scales and to explore their relationship with mechanical properties in a split-mouth design. Fresh human cadaver transverse PDL specimens of maxillary anterior teeth were categorized into cervical, middle, and apical groups. These specimens were analyzed via Masson’s trichrome staining, scanning electron microscopy, picrosirius red (PSR) staining, three-dimensional (3D) reconstruction, Raman spectroscopy, and uniaxial tensile test. Statistical analyses were performed to compare the structural, compositional, and tensile properties among the groups. Notably, the middle PDL samples exhibited superior tensile strength and higher fiber area fraction than the other two transverse sections. Despite a higher mineral-to-matrix ratio and a different collagen secondary structure, the apical PDL demonstrated a relatively weaker tensile strength, possibly associated with its discovered sparser collagen fiber areal fraction. The cervical region, characterized by a mediocre fiber areal fraction, displayed diminished tensile strength. The 3D reconstructed collagenous network model and PSR staining exposed the fiber interaction and the micropores. Microscale porosity and variations in collagen secondary structure, particularly in the apical region, suggest adaptive mechanisms for accommodating compressive forces and maintaining functional integrity. Variance in the tensile properties of samples in different force directions indicated the significant influence of fiber orientation and root level on tissue mechanics.</div></div><div><h3>Statement of significance</h3><div>This study provides critical insights into the biomechanical and structural properties of the human periodontal ligament (PDL), particularly focusing on the underexplored anterior teeth. Through advanced techniques like SEM, histological staining, 3D reconstruction, Raman spectroscopy, and tensile testing, we reveal significant regional variations in PDL collagen organization, composition, and biomechanical properties. Our findings address a crucial knowledge gap concerning the material mechanics of the PDL, offering a foundational understanding for future periodontal tissue engineering and biomimetic material development. This multi-scale analysis underscores the importance of both mesoscale structural characteristics and nanoscale molecular structures in maintaining PDL mechanical integrity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 253-265"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303143","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":"Thermosensitive chitosan-based hydrogel: A vehicle for overcoming the limitations of nose-to-brain cell therapy","authors":"Doddy Denise Ojeda-Hernández ,&nbsp;Susana Velasco-Lozano ,&nbsp;José M. Fraile ,&nbsp;J.C. Mateos-Díaz ,&nbsp;Francisco J. Rojo ,&nbsp;María Soledad Benito-Martín ,&nbsp;Belén Selma-Calvo ,&nbsp;Sarah de la Fuente-Martín ,&nbsp;Marina García-Martín ,&nbsp;María Teresa Larriba-González ,&nbsp;Mercedes Azucena Hernández-Sapiéns ,&nbsp;Alejandro A. Canales-Aguirre ,&nbsp;Jordi A. Matias-Guiu ,&nbsp;Jorge Matias-Guiu ,&nbsp;Ulises Gomez-Pinedo","doi":"10.1016/j.actbio.2024.09.002","DOIUrl":"10.1016/j.actbio.2024.09.002","url":null,"abstract":"<div><div>Cell therapy is a promising strategy for treating neurological pathologies but requires invasive methods to bypass the blood–brain barrier restrictions. The nose-to-brain route has been presented as a direct and less invasive alternative to access the brain. The primary limitations of this route are low retention in the olfactory epithelium and poor cell survival in the harsh conditions of the nasal cavity. Thus, using chitosan-based hydrogel as a vehicle is proposed in this work to overcome the limitations of nose-to-brain cell administration. The hydrogelʼs design was driven to achieve gelification in response to body temperature and a mucosa-interacting chemical structure biocompatible with cells. The hydrogel showed <em>a</em> &lt; 30 min gelation time at 37 °C and &gt;95 % biocompatibility with 2D and 3D cultures of mesenchymal stromal cells. Additionally, the viability, stability, and migration capacity of oligodendrocyte precursor cells (OPCs) within the hydrogel were maintained <em>in vitro</em> for up to 72 h. After the intranasal administration of the OPCs-containing hydrogel, histological analysis showed the presence of viable cells in the nasal cavity for up to 72 h post-administration in healthy athymic mice. These results demonstrate the hydrogel's capacity to increase the residence time in the nasal cavity while providing the cells with a favorable environment for their viability. This study presents for the first time the use of thermosensitive hydrogels in nose-to-brain cell therapy, opening the possibility of increasing the delivery efficiency in future approaches in translational medicine.</div></div><div><h3>Statement of significance</h3><div>This work highlights the potential of biomaterials, specifically hydrogels, in improving the effectiveness of cell therapy administered through the nose. The nose-to-brain route has been suggested as a non-invasive way to directly access the brain. However, delivering stem cells through this route poses a challenge since their viability must be preserved and cells can be swept away by nasal mucus. Earlier attempts at intranasal cell therapy have shown low efficiency, but still hold promise to the future. The hydrogels designed for this study can provide stem cells with a biocompatible environment and adhesion to the nasal atrium, easing the successful migration of viable cells to the brain.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 157-168"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156914","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":"Hydrogen-releasing magnesium hydrogel mitigates post laminectomy epidural fibrosis through inhibition of neutrophil extracellular traps","authors":"Rui Mei ,&nbsp;Jinpeng Sun ,&nbsp;Shuchang Cao ,&nbsp;Mohan Shi ,&nbsp;Zeyuan Song ,&nbsp;Feng Hua ,&nbsp;Gaoxin Zhou ,&nbsp;Mingshun Zhang ,&nbsp;Jun Liu","doi":"10.1016/j.actbio.2024.09.006","DOIUrl":"10.1016/j.actbio.2024.09.006","url":null,"abstract":"<div><div>Epidural fibrosis is a primary contributor to the failure of laminectomy surgeries, leading to the development of failed back surgery syndrome (FBSS). Post-laminectomy, neutrophils infiltrate the surgical site, generating neutrophil extracellular traps (NETs) that contribute to epidural fibrosis. Reactive oxygen species (ROS) play a pivotal role in mediating NETs formation. Molecular hydrogen, recognized for its selective antioxidant properties and biosafety, emerges as a potential therapeutic gas in suppressing epidural fibrosis. In this study, we developed an in-situ hydrogen release hydrogel that inhibits the formation of NETs and mitigates epidural scarring. Biodegradable magnesium (Mg) microspheres served as a hydrogen source, coated with PLGA to regulate hydrogen release. These microspheres (Mg@PLGA) were then incorporated into a PLGA-PEG-PLGA thermosensitive hydrogel (Mg@PLGA@Gel), providing a surgical implant for sustained, long-term hydrogen release. <em>In vitro</em> experiments confirmed the biocompatibility of the system, demonstrating that hydrogen produced by Mg@PLGA effectively neutralizes neutrophil intracellular ROS and inhibits NETs formation. Histological analyses, including H&amp;E staining, MRI, Masson staining, and immunohistochemistry, collectively indicate that Mg@PLGA@Gel is biocompatible and effectively inhibits epidural fibrosis post-laminectomy. Furthermore, Mg@PLGA@Gel inhibits ROS accumulation and NETs formation at the surgical site. These findings suggest that Mg@PLGA@Gel ensures continuous, therapeutic hydrogen concentration, providing relief from epidural fibrosis in a laminectomy mouse model.</div></div><div><h3>Statement of significance</h3><div><ul><li><span>•</span><span><div>The hydrogen-releasing hydrogel combines the therapeutic effects of a physical barrier with immunomodulation.</div></span></li><li><span>•</span><span><div>In situ-generated molecular hydrogen scavenges ROS caused by surgical stress and suppresses NETs formation.</div></span></li><li><span>•</span><span><div>The hydrogen-releasing hydrogel is demonstrated to exhibit high biocompatibility and inhibit epidural scar formation <em>in vivo</em>.</div></span></li></ul></div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 420-431"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303132","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":"Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions","authors":"Xinqi Zeng ,&nbsp;Yanhao Li ,&nbsp;Gang Zhao ,&nbsp;Xiaoer Wei ,&nbsp;Rongpu Wu ,&nbsp;Sa Pang ,&nbsp;Yuange Li ,&nbsp;Zaijing Tao ,&nbsp;Shuo Wang ,&nbsp;Jixian Yue ,&nbsp;Xu Chen ,&nbsp;Yajun Xu ,&nbsp;Yongjun Rui ,&nbsp;Jingyi Mi ,&nbsp;Yang Liu ,&nbsp;Jinglei Wu ,&nbsp;Jian Tian","doi":"10.1016/j.actbio.2024.09.031","DOIUrl":"10.1016/j.actbio.2024.09.031","url":null,"abstract":"<div><div>Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)–dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA.</div></div><div><h3>Statement of significance</h3><div>Peritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 197-211"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334136","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 bifunctional lactoferrin-derived amyloid coating prevents bacterial adhesion and occludes dentinal tubules via deep remineralization","authors":"Bing Sun ,&nbsp;Jiao Sun ,&nbsp;Kai Zhang ,&nbsp;Yanyun Pang ,&nbsp;Cheng Zhi ,&nbsp;Fan Li ,&nbsp;Yangyang Ye ,&nbsp;Jinglin Wang ,&nbsp;Yongchun Liu ,&nbsp;Jiayin Deng ,&nbsp;Peng Yang ,&nbsp;Xu Zhang","doi":"10.1016/j.actbio.2024.08.056","DOIUrl":"10.1016/j.actbio.2024.08.056","url":null,"abstract":"<div><div>Dentin hypersensitivity (DH) manifests as sharp and uncomfortable pain due to the exposure of dentinal tubules (DTs) following the erosion of tooth enamel. Desensitizing agents commonly used in clinical practice have limitations such as limited depth of penetration, slow remineralization and no antimicrobial properties. To alleviate these challenges, our study designed a lactoferrin-derived amyloid nanofilm (PTLF nanofilm) inspired by the saliva-acquired membrane (SAP). The nanofilm utilises Tris(2-carboxyethyl)phosphine (TCEP) to disrupt the disulfide bonds of lactoferrin (LF) under physiological conditions. The PTLF nanofilm modifies surfaces across various substrates and effectively prevents the early and stable adhesion of cariogenic bacteria, such as <em>Streptococcus mutans</em> and <em>Lactobacillus acidophilus</em>. Simultaneously, it adheres rapidly and securely to demineralized dentin surfaces, facilitating <em>in-situ</em> remineralization of HAP through a simple immersion process. This leads to the formation of a remineralized layer resembling natural dentin, with an occlusion depth of dentinal tubules exceeding 80 µm after three days. The <em>in vivo</em> and <em>vitro</em> results confirm that the PTLF nanofilm possesses good biocompatibility and its ability to exert simultaneous antimicrobial effects and dentin remineralization. Accordingly, this innovative bifunctional PTLF amyloid coating offers promising prospects for the management of DH-related conditions.</div></div><div><h3>Statement of significance</h3><div><ul><li><span>1.</span><span><div>We design a simple, fast, inexpensive, and easy-to-process PTLF nanofilm for nearly any material surface or shape.</div></span></li><li><span>2.</span><span><div>The PTLF nanofilm modifies surfaces across various substrates and effectively prevents the adhesion of cariogenic bacteria, such as Streptococcus mutans and Lactobacillus acidophilus.</div></span></li><li><span>3.</span><span><div>The abundant functional groups on the surface of PTLF nanofilm facilitate bioactive hydroxyapatite (HAP) formation and maintain stability at the HAP remineralization interface.</div></span></li></ul></div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 393-405"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147076","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 tough Janus poly(vinyl alcohol)-based hydrogel for wound closure and anti postoperative adhesion","authors":"Xiaojin Lin ,&nbsp;Zongxuan Huang ,&nbsp;Hongjian Huang ,&nbsp;Yan Fang ,&nbsp;Yunxiang Weng ,&nbsp;Zhengchao Wang ,&nbsp;Hu Zhao ,&nbsp;Haiqing Liu","doi":"10.1016/j.actbio.2024.08.049","DOIUrl":"10.1016/j.actbio.2024.08.049","url":null,"abstract":"<div><div>Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m³; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m² of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the <em>in vivo</em> adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation.</div></div><div><h3>Statement of significance</h3><div>Despite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 103-116"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147077","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":"Enhancing melanoma therapy by modulating the immunosuppressive microenvironment with an MMP-2 sensitive and nHA/GNE co-encapsulated hydrogel","authors":"Zhu Chen ,&nbsp;Hongfeng Wu ,&nbsp;Yifu Wang ,&nbsp;Yunjia Rao ,&nbsp;Jin Yan ,&nbsp;Bin Ran ,&nbsp;Qin Zeng ,&nbsp;Xiao Yang ,&nbsp;Jun Cao ,&nbsp;Huan Cao ,&nbsp;Xiangdong Zhu ,&nbsp;Xingdong Zhang","doi":"10.1016/j.actbio.2024.08.055","DOIUrl":"10.1016/j.actbio.2024.08.055","url":null,"abstract":"<div><div>The immunosuppressive tumor microenvironment, such as lactic acid and matrix metalloproteinases (MMPs) overexpression, has been well confirmed to be adverse for tumor therapy. In current study, a tumor microenvironment modulatory hydrogel was successfully developed to treat melanoma by taking advantage of the synergistic effects of nano-hydroxyapatite (nHA) with well-documented selective anti-tumor action, lactate dehydrogenase A inhibitor (R)-GNE-140 (GNE), and matrix metalloproteinase-2 (MMP-2) sensitive peptide. The hydrogel was acquired by the reaction of 4-arm-polyethylene glycol-maleic anhydride (4-arm-PEG-MAL) and MMP-2 sensitive peptide (CC-14), in which nHA and GNE were co-encapsulated physically. The <em>in vitro</em> degradation tests confirmed the accelerated release of nHA and GNE from the hydrogel under less-acidic (pH 6.8) and MMP-2 containing conditions compared to those neutral or without MMP-2 conditions, demonstrating the pH and MMP-2 responsive properties of as-prepared hydrogel. Findings from <em>in vitro</em> cell experiments revealed that the hydrogel could stop the proliferation of melanoma cells by stacking cell cycle <em>via</em> lactic acid metabolic dysregulation and boosting cell apoptosis <em>via</em> nHA direct killing effect. Moreover, after hydrogel treatment, the rate of migration and aggressiveness of melanoma cells both reduced significantly. An <em>in vivo</em> anti-melanoma study showed that the hydrogel could inhibit tumor growth significantly and result in more CD8⁺ T cells and antigen-presenting cells but less T_reg cells infiltration, ultimately leading to an enhanced therapeutic efficacy. As thus, the fabricated hydrogel demonstrated great promise for treating melanoma and could be a new potent strategy for efficient melanoma therapy.</div></div><div><h3>Statement of significance</h3><div>Nano-hydroxyapatite (nHA) has the capability of selectively killing cancer cells. The study reported a tumor microenvironment (TME) modulatory hydrogel with the goal of enhancing melanoma therapy efficacy by combining nHA administration with immunosuppressive microenvironment modulation. The hydrogel demonstrated pH and MMP-2 sensitivity. Hence, controlled release of nHA and lactate dehydrogenase A inhibitor (GNE) could be observed, and <em>in situ</em> MMP-2 consumption at the tumor site occurred. The hydrogel effectively inhibited the growth of melanoma cells. Furthermore, hydrogel increased the production of CD8⁺ T cells and antigen-presenting cells while decreasing the infiltration of T_reg cells at the tumor site. This could transform the initial “cold” tumor into a “hot” tumor, ultimately resulting in an enhanced therapeutic effect.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 79-92"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147078","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 dual-pathway pyroptosis inducer based on Au–Cu2-xSe@ZIF-8 enhances tumor immunotherapy by disrupting the zinc ion homeostasis","authors":"Xiang Yan ,&nbsp;Cheng Chen ,&nbsp;Yiping Ren ,&nbsp;Tianyu Su ,&nbsp;Han Chen ,&nbsp;Dehong Yu ,&nbsp;Yuqi Huang ,&nbsp;Minghao Chao ,&nbsp;Guoquan Wu ,&nbsp;Guan Jiang ,&nbsp;Fenglei Gao","doi":"10.1016/j.actbio.2024.09.015","DOIUrl":"10.1016/j.actbio.2024.09.015","url":null,"abstract":"<div><div>The regulation of intracellular ionic homeostasis to trigger antigen-specific immune responses has attracted extensive interest in tumor therapy. In this study, we developed a dual-pathway nanoreactor, Au-Cu_2-xSe@ZIF-8@P18 NPs (ACS-Z-P NPs), which targets danger-associated molecular patterns (DAMPs) and releases Zn²⁺ and reactive oxygen species (ROS) within the tumor microenvironment (TME). Zn²⁺ released from the metal–organic frameworks (MOFs) was deposited in the cytoplasm, leading to aberrant transcription levels of intracellular zinc-regulated proteins and DNA damage, thereby inducing pyroptosis and immunogenic cell death (ICD) dependent on caspase1/gasdermin D (GSDMD) pathway. Furthermore, upon laser irradiation, ACS-Z-P NPs could break through the limitations of inherent defects of immunosuppression in TME, enhance ROS generation through a Fenton-like reaction cascade, which subsequently triggered the activation of inflammatory vesicles and the release of damage-associated molecular patterns (DAMPs). This cascade effect led to the amplification of pyroptosis and immunogenic cell death (ICD), thereby remodeling the immunosuppressed TME. Consequently, this process improved dendritic cell (DC) antigen presentation and augmented anti-tumor T-cell responses, effectively initiating antigen-specific immune responses and further enhancing pyroptosis and ICD. This study explores the therapeutic properties of these mechanisms in detail.</div></div><div><h3>Statement of significance</h3><div>The synthesized Au-Cu_2-xSe@ZIF-8@P18 nanoparticles (ACS-Z-Ps) can effectively enhance the bodyʼs immune response by regulating zinc ion levels within cells. This regulation leads to abnormal levels of zinc-regulated protein transcription and DNA damage, which induces cellular pyroptosis. As a result, antigen presentation to dendritic cells (DCs) is improved, and anti-tumor T-cell responses are enhanced.</div><div>The ACS-Z-P NPs overcome the limitations of ROS deficiency and immunosuppression in the tumor microenvironment by using H₂O₂ in the tumor microenvironment through a Fenton-like reaction. This leads to an increased production of ROS and O₂, remodeling of the immunosuppressed tumor microenvironment, and enhanced induction of cell pyroptosis and immunogenic cell death.</div><div>ACS-Z-P NPs targeted B16 cells using the photosensitizer P18 in combination with PDT treatment. This approach significantly inhibited the proliferation of B16 cells and effectively inhibited tumor growth.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 329-343"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303122","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":"Armed on the back: Hidden biomineralized scales in the ventral girdle of chiton Acanthopleura loochooana","authors":"Haipeng Liu,&nbsp;Chuang Liu","doi":"10.1016/j.actbio.2024.09.009","DOIUrl":"10.1016/j.actbio.2024.09.009","url":null,"abstract":"<div><div>Flexible protective armors are found in large animals such as fish skins, snake skins, and pangolin scales. For small-sized invertebrates, such armors are paid less attention and overlooked. Chitons, a type of marine mollusk, possess mineralized armors covering the whole dorsal body. The dorsal scales in the girdle tissue are well known, in this study, we reported hidden mineralized scales in the ventral side of chiton <em>Acanthopleura loochooana</em> girdles for the first time. The ventral surface is covered with scales with ca. 40 μm in length, forming continuous but overlapped scales. Additionally, scales are formed from aragonitic spicule-like and square-like scales, embedded in the cuticle layer. Nanoindentation testing results showed that the hardness and elastic modulus of ventral scales were ∼20 % higher compared to those in the dorsal scales, exhibiting good hardness and wear resistance. The combination of the ventral scales and cuticle, along with the regular arrangement of ventral scales, may allow chitons to simultaneously address complex and variable attachment interfaces while also providing wear-resistant protection. This study provides insights for designing protective structures that balance flexibility and durability.</div></div><div><h3>Statement of significance</h3><div>Biomineralization is universal in nature and provides protection and support for animals. However, mineralization of dermal skin is not commonly seen. Herein, for the first time, we reported hidden minerals covering the whole ventral side of skin in a small marine animal, chitons. Calcium carbonate minerals are arranged regularly and manifest different morphology in different regions. Additionally, these minerals are embedded in a continuous cuticle layer covering the whole animal. The material also indicates a higher wear-resistant property. This study extends our understanding of the diverse functionality of biominerals and provides a prototype for designing wear-resistant materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 266-275"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303126","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":"Stimulus-responsive drug delivery nanoplatforms for inflammatory bowel disease therapy","authors":"Jiang Long ,&nbsp;Xiaoya Liang ,&nbsp;Zuojin Ao ,&nbsp;Xiao Tang ,&nbsp;Chuang Li ,&nbsp;Kexin Yan ,&nbsp;Xin Yu ,&nbsp;Ying Wan ,&nbsp;Yao Li ,&nbsp;Chunhong Li ,&nbsp;Meiling Zhou","doi":"10.1016/j.actbio.2024.09.007","DOIUrl":"10.1016/j.actbio.2024.09.007","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD.</div></div><div><h3>Statement of significance</h3><div>This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 27-47"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303139","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}