Acta Biomaterialia最新文献

{"title":"Magnetoactive elastomer-based dynamic urethral support device for stress urinary incontinence","authors":"Seelay Tasmim ,&nbsp;Asha Baten ,&nbsp;Manivannan Sivaperuman Kalairaj ,&nbsp;Suitu Wang ,&nbsp;Philippe E. Zimmern ,&nbsp;Taylor H. Ware","doi":"10.1016/j.actbio.2024.11.039","DOIUrl":"10.1016/j.actbio.2024.11.039","url":null,"abstract":"<div><div>Stress urinary incontinence (SUI) is the involuntary leakage of urine in response to increased intra-abdominal pressure during episodes of exertion. A common treatment method for SUI is sling implantation underneath the urethra to provide support. Most current sling procedures, however, cannot adjust urethral tension postoperatively. To address this limitation, we designed a soft magnetoactive elastomer (MAE) device capable of changing shape in response to moderate magnetic fields. To ensure shape change after fibrotic scar tissue encapsulation, MAE devices were embedded in agar gels with different stiffnesses, and their shape change was studied in response to up to 200 mT magnetic fields. A simple in vitro model of the lower urinary tract was designed to study device performance. Flow time was measured as a function of pressure in the simulated bladder as the model system leaked before and after activating sling with a hand-held magnet. MAE devices embedded in agar gel (100 kPa) in hammock-like configuration achieved 4.7% ± 1.1% change in height. Devices with silica-coated magnetic particles showed minimal loss in mass after two weeks in accelerated oxidative (2.36% ± 1.55%) and hydrolytic (0.58% ± 0.25%) conditions. Placing a sling under the model urethra provided urethral support; thus, increasing its resistance to flow. Normalized flow time significantly reduced from 1.56 ± 0.18 to 1.11 ± 0.16 when magnetic field was applied, indicating urethral support modulation at 60 cm-H₂O. This dynamic sling, powered externally with physiologically safe magnetic fields, allowed for urethral support modulation in a model of the lower urinary tract.</div></div><div><h3>Statement of significance</h3><div>Stress urinary incontinence (SUI) affects up to half the adult women during their lifetime, and slings are commonly used to treat severe cases. While sling implantation is minimally invasive and offers moderate to high cure rates, long-term sling complications, such as urine retention, remain a significant concern. Available adjustable SUI devices often require invasive surgeries, implantable electronics, and multiple mechanical components, increasing the overall invasiveness. Here, we report a proof of concept for using shape-morphing biomaterials to fabricate a dynamic device that can provide continence support and be triggered to change shape, enabling complete voiding. Such a dynamic device may prevent many complications associated with traditional slings and improve quality of life for women suffering from severe SUI.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 336-351"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712198","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":"Regenerated fat induced by a decellularized adipose matrix can survive long-term in vivo","authors":"Jiayi Feng ,&nbsp;Su Fu ,&nbsp;Jie Luan","doi":"10.1016/j.actbio.2024.09.028","DOIUrl":"10.1016/j.actbio.2024.09.028","url":null,"abstract":"<div><div>Decellularized adipose matrix (DAM) is considered to be the most potential biological scaffold for soft tissue repair and reconstruction, as it is able to induce the regeneration of adipose tissue in situ in adulthood. But how does this adipose tissue regeneration happen and develop <em>in vivo</em>? Is it the same as the original autologous one? Temporary existence or long-term survival? These are the key questions that will determine the future applications of DAM. In this study, we investigated the composition, structure and biomechanical properties of DAM before implanting it into the subcutaneous back of immunodeficient mice. The entire regeneration process <em>in vivo</em> was closely monitored histologically from 3 days to 1 year after implantation, including fat regeneration, vascular growth, inflammatory responses, and matrix degradation and remodeling. Transcriptome sequencing was used to analyze the difference in gene expression between regenerated fat and autologous fat at different periods. The results showed that the DAM-induced regenerated fat first appeared at 1 w and remained stable over 6 m, indicating remarkable similarity to autologous fat at the later stages of implantation. And about (18.3 ± 29.3) % of the regenerated adipocytes were still viable after one year. The process of adipogenesis was enhanced by the decrease in inflammatory infiltration and proceeded in parallel with angiogenesis.</div></div><div><h3>Statement of significance</h3><div>The decellularized adipose matrix (DAM) is the only biological scaffold that can spontaneously generate adipocytes <em>in vivo</em> without the need to add exogenous cells. However, in the previous studies, the longest DAM-related animal experiments were about 3 months. The different stages and characteristics of DAM implantation cannot be fully captured. Comprehensive preclinical researches on the initiation, characteristics, and long-term outcomes of DAM-induced adipose tissue regeneration in adulthood is crucial.</div><div>In this study, we closely observed various aspects of the entire process <em>in vivo</em> from 3 days to 1 year after implantation including fat regeneration, vascular growth, inflammatory reactions as well as matrix degradation and remodeling. The thorough research will contribute to the understanding of stability and dynamic remodeling of DAM regeneration models.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 233-243"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303138","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":"Endochondral ossification: Insights into the cartilage mineralization processes achieved by an anhydrous freeze substitution protocol","authors":"Suwimon Boonrungsiman ,&nbsp;Christopher Allen ,&nbsp;Fabio Nudelman ,&nbsp;Sandra Shefelbine ,&nbsp;Colin Farquharson ,&nbsp;Alexandra E Porter ,&nbsp;Roland A Fleck","doi":"10.1016/j.actbio.2024.11.015","DOIUrl":"10.1016/j.actbio.2024.11.015","url":null,"abstract":"<div><div>Growth plate cartilage (GP) serves as a dynamic site of active mineralization and offers a unique opportunity to investigate the cell-regulated matrix mineralization process. Transmission electron microscopy (TEM) provides a means for the direct observation of these mechanisms, offering the necessary resolution and chemical analysis capabilities. However, as mineral crystallinity is prone to artifacts using aqueous fixation protocols, sample preparation techniques are critical to preserve the mineralized tissue in its native form. We optimized cryofixation by high-pressure freezing followed by freeze substitution in anhydrous acetone containing 0.5 % uranyl acetate to prepare murine GP for TEM analysis. This sample preparation workflow maintains cellular and extracellular protein structural integrity with sufficient contrast for observation and without compromising mineral crystallinity. By employing appropriate sample preparation techniques, we were able to observe two parallel mineralization processes driven by chondrocytes: 1) intracellular- and 2) extracellular-originating mineralized vesicles. Both mechanisms are based on sequestering calcium phosphate (CaP) within a membrane-limited structure, <em>albeit</em> originating from different compartments of the chondrocytes. In the intracellular originating pathway, CaP accumulates within mitochondria as globular CaP granules, which are incorporated into intracellular vesicles (500–1000 nm) and transported as granules to the extracellular matrix (ECM). In contrast, membrane budding vesicles with a size of approximately 100–200 nm, filled with needle-shaped minerals were observed only in the ECM. Both processes transport CaP to the collagenous matrix <em>via</em> vesicles, they can be differentiated based on the vesicle size and mineral morphologies. Their individual importance to the cartilage mineralization process is yet to be determined.</div></div><div><h3>Statement of Significance</h3><div>We do not fully understand the process by which epiphyseal cartilage mineralizes - a vital step in endochondral bone formation. Previous work has proposed that mitochondria and intracellular vesicles are storage sites for the delivery of mineral to collagen fibrils. However, these concepts are founded on results from <em>in vitro</em> models of mineralization; no prior work has observed mineral-containing intracellular vesicles or mitochondria in developing epiphyseal cartilage. Here we developed a new cryofixation preparation route for transmission electron microscopy (TEM) imaging that has disclosed a cell-regulated process of mineralization in epiphyseal cartilage. High resolution TEM images revealed an involvement of mitochondria and intracellular and extracellular vesicles in delivering transient mineral phases to the collagen fibrils to promote cartilage mineralization.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 149-157"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634059","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":"Interleukin-12 decorated nanosized semiflexible Immunofilaments enable directed targeting and augmented IFNγ responses of natural killer cells","authors":"Lea Weiss ,&nbsp;Marjolein Schluck ,&nbsp;René Classens ,&nbsp;Paul K.J.D. de Jonge ,&nbsp;Anniek van der Waart ,&nbsp;Khue G. Nguyen ,&nbsp;Tam T. Nguyen ,&nbsp;David A. Zaharoff ,&nbsp;Karl-Johan Malmberg ,&nbsp;Harry Dolstra ,&nbsp;Carl G. Figdor ,&nbsp;Ebba Sohlberg ,&nbsp;Roel Hammink","doi":"10.1016/j.actbio.2024.11.012","DOIUrl":"10.1016/j.actbio.2024.11.012","url":null,"abstract":"<div><div>Immunotherapies are a powerful strategy to treat cancer by modulating the immune system to raise an anti-tumor immune response. A prime example of immunotherapies are cytokines - small immunomodulatory molecules that are widely used to stimulate immune cells. Undirected administration of cytokines, however, can cause severe side effects, preventing the use of potent cytokines, such as Interleukin (IL)-12, which induces IFNγ responses by cytotoxic effector lymphocytes, including NK cells. Biomaterials, like nanoparticles, can encapsulate IL-12 and accumulate at the tumor site to alleviate side effects. Yet, the released IL-12 might not be directly targeted to extracellular IL-12 receptors on the specific effector cells, thereby potentially compromising the cytokine's therapeutic efficacy. Here, we develop a polymer-based platform to target NK cells, which we call immunofilaments. Immunofilaments are nanosized linear polymers that present an anti-CD16 antibody and IL-12 effectively to NK cells and lead to synergistic NK cell activation as highlighted by an increase in TNFα and IFNγ production and upregulation of multiple activation markers, including CD25, CD69, and degranulation marker CD107a. NK cell proliferation is enhanced in the presence of both anti-CD16 antibody and IL-12 compared to giving IL-12 separately. Finally, we demonstrate that the IF platform is suitable for <em>in vivo</em> applications, as immunofilaments readily activate human NK cells upon administration to mice.</div></div><div><h3>Statement of Significance</h3><div>IL-12 is a potent cytokine that stimulates IFNγ responses in NK cells, which supports an anti-tumor immune response. Due to its high potency, the delivery of IL-12 needs to be highly controlled to prevent severe adverse side effects, which can be achieved by using biomaterials. This study shows that nanosized polymers termed Immunofilaments can be used to immobilize IL-12 and effectively target and activate NK cells by co-conjugation of anti-CD16 antibodies. This work is a prime example of careful engineering of innovative biomaterials to improve immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 386-397"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634259","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":"Targeted CRISPR regulation of ZNF865 enhances stem cell cartilage deposition, tissue maturation rates, and mechanical properties in engineered intervertebral discs","authors":"Hunter Levis ,&nbsp;Christian Lewis ,&nbsp;Matthew Fainor ,&nbsp;Ameerah Lawal ,&nbsp;Elise Stockham ,&nbsp;Jacob Weston ,&nbsp;Niloofar Farhang ,&nbsp;Sarah E. Gullbrand ,&nbsp;Robby D. Bowles","doi":"10.1016/j.actbio.2024.11.007","DOIUrl":"10.1016/j.actbio.2024.11.007","url":null,"abstract":"<div><div>Cell and tissue engineering based approaches have garnered significant interest for treating intervertebral disc degeneration and associated low back pain due to the substantial limitations of currently available clinical treatments. Herein we present a clustered regularly interspaced short palindromic repeats (CRISPR)-guided gene modulation strategy to improve the therapeutic potential of cell and tissue engineering therapies for treating intervertebral disc disease. Recently, we discovered a zinc finger (ZNF) protein, ZNF865 (BLST), which is associated with no in-depth publications and has not been functionally characterized. Utilizing CRISPR-guided gene modulation, we show that ZNF865 regulates cell cycle progression and protein processing. As a result, regulating this gene acts as a primary titratable regulator of cell activity. We also demonstrate that targeted ZNF865 regulation can enhance protein production and fibrocartilage-like matrix deposition in human adipose-derived stem cells (hASCs). Furthermore, we demonstrate CRISPR-engineered hASCs ability to increase GAG and collagen <strong>II</strong> matrix deposition in human-size tissue-engineered discs by 8.5-fold and 88.6-fold, respectively, while not increasing collagen X expression compared to naive hASCs dosed with growth factors. With this increased tissue deposition, we observe significant improvements in compressive mechanical properties, generating a stiffer and more robust tissue. Overall, we present novel biology on ZNF865 and display the power of CRISPR-cell engineering to enhance strategies treating musculoskeletal disease.</div></div><div><h3>Statement of significance</h3><div>This work reports on a novel gene, ZNF865 (also known as BLST), that when regulated with CRISPRa, improves cartilagenous tissue deposition in human sized tissue engineering constructs. Producing tissue engineering constructs at human scale has proven difficult, and this strategy presents a broadly applicable tool to enhance a cells ability to produce tissue at these scales, as we saw an ∼8–88 fold increase in tissue deposition and significantly improved biomechanics in large tissue engineered intervertebral disc compared to traditional growth factor differentiation methods. Additionally, this work begins to elucidate the biology of this novel zinc finger protein, which appears to be critical in regulating cell function and activity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 276-291"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634276","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":"Manganese-doped liquid metal nanoplatforms for cellular uptake and glutathione depletion-enhanced photothermal and chemodynamic combination tumor therapy","authors":"Shuai Wang ,&nbsp;Yang Zou ,&nbsp;Liefeng Hu ,&nbsp;Yonggang Lv","doi":"10.1016/j.actbio.2024.11.010","DOIUrl":"10.1016/j.actbio.2024.11.010","url":null,"abstract":"<div><div>Chemodynamic therapy (CDT) involves the catalysis of <em>in situ</em> overexpressed hydrogen peroxide (H₂O₂) into highly toxic reactive oxygen species (ROS) to treat tumors. However, the efficacy of CDT is greatly hampered by limited cellular internalization efficiency, ROS scavenging by glutathione (GSH), and slow reaction rate. To overcome the current limitations of CDT, a manganese-doped and polyethylene glycol (PEG)-modified liquid metal (LM)-silica nanoplatform (labeled as Mn-LMOP) with varying stiffness is constructed to achieve synergistic photothermal therapy (PTT) and CDT, which can further induce immunogenic cell death (ICD) in tumors to enhance the anti-tumour effects. Significantly, benefiting from the increased stiffness, the Mn-LMOP nanoparticles (NPs) can enhance cellular uptake and lysosomal escape, and gradually accumulate in tumor sites. Moreover, manganese-doped NPs exhibite good photothermal effects and can rapidly reacte with intratumoral GSH to produce Mn²⁺, inhibiting GSH-mediated ROS clearance and promoting the efficiency of CDT. This combined treatment strategy can activate the immune response of the tumors, which holds the promise of photothermal/chemodynamic/immune multimodal therapeutic effects. This LM-based nanosystem will provide a paradigm for enhanced CDT/PTT combination anti-tumour efficacy.</div></div><div><h3>Statement of significance</h3><div>Chemodynamic therapy (CDT) is a promising drug-free treatment approach characterized by its low invasiveness and minimal side effect. However, CDT encounters challenges such as high levels of glutathione (GSH), low Fenton-like reaction rate, and inefficient cellular uptake in tumor tissues. Here, a manganese-doped liquid metal (LM) nanomaterial was designed to achieve synergistic photothermal therapy (PTT) and CDT. This innovative strategy enhanced cellular uptake by adjusting the mechanical property of nanoparticles (NPs) and facilitated the consumption of GSH, while simultaneously accelerating the Fenton-like reaction rate with the assistance of PTT-mediated hyperthermia. This combined CDT/PTT strategy also activated the immune response within the tumor, demonstrating significant therapeutic potential.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 369-385"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634261","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":"Repair effects of thermosensitive hydrogels combined with iPSC-derived corneal endothelial cells on rabbit corneal endothelial dysfunction","authors":"Jinhua Chi ,&nbsp;Shuo Wang ,&nbsp;Ruibao Ju ,&nbsp;Shanshan Li ,&nbsp;Chenqi Liu ,&nbsp;Mingyu Zou ,&nbsp;Tianjiao Xu ,&nbsp;Yanting Wang ,&nbsp;Zhiwen Jiang ,&nbsp;Chaozhong Yang ,&nbsp;Baoqin Han","doi":"10.1016/j.actbio.2024.11.021","DOIUrl":"10.1016/j.actbio.2024.11.021","url":null,"abstract":"<div><div>Considering the limitations of human corneal endothelial cell proliferation as well as the severe shortage of corneal donations, it is imperative to develop improved methods of corneal endothelial cell transplantation. The purpose of this study was to construct a modified corneal endothelial cell transplantation approach using thermosensitive hydrogels combined with induced pluripotent stem cells (iPSCs)-derived human corneal endothelial cells (hCECs). In this study, thermosensitive hydrogels hydroxypropyl chitin/carboxymethyl chitosan (HPCH/CMCS) were fabricated, and their hydrogels properties and biocompatibility were investigated. Our results demonstrated that HPCH/CMCS hydrogels exhibited superior transparency, appropriate mechanical properties and favorable biocompatibility. A two-step induction method of small molecule compounds was employed, by which iPSCs were differentiated into hCECs via neural crest cells (NCCs). Additionally, a rabbit corneal endothelial dysfunction model was established <em>in vivo</em>, aiming to evaluate the safety and effectiveness of the combined method. Slit lamp microscope results indicated that significant transparency improvement could be noted in HPCH/CMCS/hCECs group (<em>P</em> = 0.006), whereas the corneal transparency was not homogeneous in different areas. Moreover, histological examinations and immunofluorescence analysis revealed that HPCH/CMCS/hCECs group showed a higher density of corneal endothelial cells and positive expressions of related markers. This study may provide ideas and experimental basis for the combined application of hydrogels and iPSC-derived corneal endothelial cells for corneal endothelial dysfunction.</div></div><div><h3>Statement of Significance</h3><div>Corneal transplantation is the most effective treatment for corneal endothelial dysfunction, which is challenged by issues such as corneal donor shortages and immune rejection. In this study, we proposed a combined transplantation method of cells and hydrogels for corneal endothelial dysfunction. We modified the protocols to obtain corneal endothelial cells from iPSCs by a two-step induction method. Besides, thermosensitive hydrogels with satisfactory biocompatibility and degradability were fabricated as fixation and support carriers of iPSC-derived corneal endothelial cells for <em>in vivo</em> transplantation. Experimental results demonstrated that this method could locally repair corneal endothelial dysfunction in rabbits, with the repaired corneas expressing relevant markers. This study presented a preliminary attempt to combine hydrogels and cells for corneal endothelial dysfunction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 216-232"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650021","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":"Deoxygenated hydroxyapatite inhibits macrophage inflammation through fibronectin restricted adsorption","authors":"Jingxuan Zhou ,&nbsp;Fanyu Zhang ,&nbsp;Qinchao Tang ,&nbsp;Taomin Zhu ,&nbsp;Yueqi Ni ,&nbsp;Qian Wu ,&nbsp;Qunli Liu ,&nbsp;Runlin Zhu ,&nbsp;Tianman Wang ,&nbsp;Yufeng Zhang ,&nbsp;Xiaoxin Zhang ,&nbsp;Hong He","doi":"10.1016/j.actbio.2024.11.026","DOIUrl":"10.1016/j.actbio.2024.11.026","url":null,"abstract":"<div><div>Macrophages can determine the ultimate outcome of the foreign body reaction (FBR). Although researchers confirmed that differences in the elemental composition of the implant interface can lead to varying levels of biological function, the mechanism underlying the polarization directions of macrophages induced by varying oxygen proportions remains unclear. This research presented the fabrication of a deoxygenated hydroxyapatite (dHAP) surface to investigate the impact of oxygen content on macrophage activation. The dHAP surface exhibited a pronounced inhibitory effect on the inflammatory activation of macrophages when compared to the HAP surface. Results from total internal reflection microscopy (TIRFM) and molecular dynamic (MD) simulation have revealed that the significant extracellular matrix adhesion protein, Fibronectin (Fn), showed a lower level of adsorption on dHAP surfaces. The Arg-Gly-Asp (RGD) structural domain showed a reduction in the exposure. The diminished adhesion capacity and impaired active site recognition ability of Fn resulted in lower activation of the integrin-focal adhesion kinase (FAK) pathway of macrophages on the dHAP surface, thereby suppressing the inflammation. In summary, this work explains the mechanism of the FBR impacted by the proportion of oxygen at the protein level. It also introduces a new approach to enhance the compatibility of biomaterials.</div></div><div><h3>Statement of Significance</h3><div>Macrophages are key in the foreign body response (FBR). Researches indicate that implant material's elemental interface content can regulate the functionality of biomaterials, but the mechanism of this regulation is unclear. To study the relationship between the elemental content at the interface and macrophages in the FBR, we prepared a deoxygenated hydroxyapatite (dHAP). Our results showed that the dHAP surface inhibited the adsorption behavior and changed the orientation of an ECM protein—fibronectin (Fn)—as well as the exposure of fewer active sites of the Arg-Gly-Asp (RGD) sequence, leading to less integrin activation. And then, the activation of the integrin- focal adhesion kinase (FAK) signaling pathway was reduced, leading to a greater activation of macrophages towards a pro-regenerative direction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 177-188"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694035","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":"Race for the surface between THP-1 macrophages and Staphylococcus aureus on various titanium implants with well-defined topography and wettability","authors":"Adam Benedict Turner ,&nbsp;Paula Milena Giraldo-Osorno ,&nbsp;Yohan Douest ,&nbsp;Liliana Andrea Morales-Laverde ,&nbsp;Carl Anton Bokinge ,&nbsp;Farah Asa'ad ,&nbsp;Nicolas Courtois ,&nbsp;Anders Palmquist ,&nbsp;Margarita Trobos","doi":"10.1016/j.actbio.2024.11.013","DOIUrl":"10.1016/j.actbio.2024.11.013","url":null,"abstract":"<div><div>Gristina <em>et al</em>. (1987) suggested that the fate of a biomaterial is decided in a “race for the surface” between pathogens and the host. To gain deeper insight into the mechanisms behind this concept, we investigated the “race for the surface” across three co-culture scenarios with THP-1 macrophages and <em>Staphylococcus aureus</em> (1:1 ratio), varying the order of addition: (i) simultaneous, (ii) macrophages first, and (iii) <em>S. aureus</em> first, on six Ti6Al4V-ELI surfaces modified with specific topographies and wettability. The outcome of the race for the surface was not influenced by these biomaterials but by the chronological introduction of macrophages and <em>S. aureu</em>s. When macrophages and <em>S. aureus</em> arrived simultaneously, macrophages won the race, leading to the lowest number of viable <em>S. aureus</em> through rapid phagocytosis and killing. When macrophages arrived and established first, macrophages still prevailed but under greater challenge resulting from the lower bacterial killing efficiency of adherent macrophages and numerous viable intracellular bacteria, supporting the concept of the so-called immunocompromised zone around implants (upregulation of TLR-2 receptor and pro-inflammatory IL-1β). When <em>S. aureus</em> arrived first establishing a biofilm, bacteria won the race, leading to macrophage dysfunction and cell death (upregulation of FcγR and TLR-2 receptors, NF-κB signaling, NOX2 mediated reactive oxygen species), contributing to a persistent biofilm phenotype (upregulation of <em>clfA, icaA, sarA</em>, downregulation of <em>agrA, hld, lukAB</em>) and intracellular survival of <em>S. aureus</em> (<em>lipA</em> upregulation). The clinical implications are bacterial colonization of the implant and persistence of intracellular bacteria in periprosthetic tissues, which can lead to infection chronicity.</div></div><div><h3>Statement of Significance</h3><div>Gristina <em>et al</em>. (1987) suggested that the fate of a biomaterial is decided in a “race for the surface” between bacterial pathogens and host cells. There is a lack of <em>in vitro</em> co-culture models and knowledge on macrophage-<em>S. aureus</em> interactions on biomaterial surfaces, and no studies have evaluated the expression of virulence factors in <em>S. aureus</em> biofilms.</div><div>We have successfully developed co-culture models and molecular panels, and elucidated important cellular and molecular interactions between macrophages and <em>S. aureus</em> on a broad range of titanium biomaterials with well-defined surface topography and wettability. Our findings highlight the critical role of biofilm formation and the chronological order of bacteria or macrophage arrival in determining the fate of the race for the surface.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 113-139"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634265","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":"Characterization of human melanoma skin cancer models: A step towards model-based melanoma research","authors":"Nicoline Dorothea Daugaard ,&nbsp;Rikke Tholstrup ,&nbsp;Jakob Rask Tornby ,&nbsp;Sofie Marchsteiner Bendixen ,&nbsp;Frederik Tibert Larsen ,&nbsp;Daniela De Zio ,&nbsp;Mike Bogetofte Barnkob ,&nbsp;Kim Ravnskjaer ,&nbsp;Jonathan R. Brewer","doi":"10.1016/j.actbio.2024.11.018","DOIUrl":"10.1016/j.actbio.2024.11.018","url":null,"abstract":"<div><div>Advancing 3D in vitro human tissue models is crucial for biomedical research and drug development to address the ethical and biological limitations of animal testing. Recently, 3D skin models have proven to be effective for studying serious skin conditions, such as melanoma. For these advanced models to be applicable in preclinical studies, thorough characterization is essential to understand their applicability and limitations.</div><div>In this study, we used bioimaging and RNA sequencing to assess the architecture and transcriptomic profiles of skin models, including models with melanoma. Our results indicated that these models closely mimicked skin morphology and gene expression patterns. The full-thickness (FT) model shows a superior resemblance to the human skin, particularly in basement membrane formation and cellular interactions.</div><div>The integrity of the skin-like properties and gene expression signatures of both skin and melanoma cells were preserved upon the integration of melanoma cells, establishing these models as robust platforms for cancer research. The responsiveness of the FT melanoma models to vemurafenib treatment was successfully monitored, demonstrating their validity as a reliable, reproducible, and humane tool for pharmacological testing and drug development. Furthermore, the transcriptomic data showed that skin models with cancer spheroids had upregulated genes linked to aggressive and resilient cancer behavior compared to spheroids alone. This emphasizes the importance of the microenvironment in cancer progression and suggests that 3D skin models can serve to uncover mechanisms and therapeutic targets that are not detectable in simpler systems.</div></div><div><h3>Statement of significance</h3><div>This study introduces advanced, ethically sound skin and melanoma models as alternatives to animal testing in drug discovery. By thoroughly characterizing these models using bioimaging and RNA sequencing, we demonstrate their close resemblance to human skin, particularly in full-thickness models. These models not only replicate the complex cellular interactions and gene expression patterns of human tissue but also maintain robustness after melanoma integration. Our findings highlight the potential of these models in revealing cancer mechanisms and therapeutic targets, offering a significant impact on melanoma research and preclinical testing.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 308-324"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645284","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}