Acta Biomaterialia最新文献

{"title":"Mitigating adverse effects of Cu-containing intrauterine devices using a highly biocompatible Cu5Fe alloy","authors":"Lijun Yang ,&nbsp;Guo Bao ,&nbsp;Cancan Yao ,&nbsp;Tian Diao ,&nbsp;Zhenning Su ,&nbsp;Tingting Liu ,&nbsp;Guannan Li ,&nbsp;Gonglei Wang ,&nbsp;Xihua Chen ,&nbsp;Xiangbo Xu ,&nbsp;Bing Sun ,&nbsp;Xiaoxue Xu ,&nbsp;Bin He ,&nbsp;Yufeng Zheng","doi":"10.1016/j.actbio.2024.09.022","DOIUrl":"10.1016/j.actbio.2024.09.022","url":null,"abstract":"<div><div>Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu²⁺. To minimize the burst release, in this study, we designed a series of Cu–Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu–Fe alloys and UFG Cu–Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and <em>in vitro</em> cytotoxicity. With careful comparison and selection, we chose the CG Cu–5Fe and UFG Cu–5Fe for <em>in vivo</em> tests using rat model, including tissue biocompatibility, <em>in vivo</em> corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu–5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu–5Fe alloys exhibited dramatic suppression of Cu²⁺ release in simulated uterine fluid for the long-term immersion process. The <em>in vivo</em> tissue compatibility was significantly improved with both CG and UFG Cu–5Fe alloys implanted in the rats’ uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu–5Fe alloys can be the promising candidate material for Cu-IUD.</div></div><div><h3>Statement of significance</h3><div>A highly biocompatible Cu–Fe alloy was designed and fabricated for Cu-containing intrauterine devices (Cu-IUD). With 5 wt% Fe, the burst release of Cu²⁺ is inhibited due to the formed galvanic cell of Cu and Fe, resulting in earlier release of Fe³⁺. As Fe is the most abundant essential trace element of human body, it can mitigate the toxic effects of Cu²⁺, thus significantly improving both <em>in vitro</em> cell compatibility and <em>in vivo</em> tissue compatibility. More importantly, the Cu–5Fe alloy exhibits 100 % contraceptive efficiency as the CG Cu, but with greatly reduced adverse effects to the uterus tissues. An advanced Cu-IUD can be developed using Cu–Fe alloys.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 651-667"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373748","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":"An optical system for cellular mechanostimulation in 3D hydrogels","authors":"Rahul Sreedasyam ,&nbsp;Bryce G. Wilson ,&nbsp;Patricia R. Ferrandez ,&nbsp;Elliot L. Botvinick ,&nbsp;Vasan Venugopalan","doi":"10.1016/j.actbio.2024.09.050","DOIUrl":"10.1016/j.actbio.2024.09.050","url":null,"abstract":"<div><div>We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca²⁺ signaling following exposure to an impulsive mechanical stimulus provided by a single 250 µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca²⁺ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy.</div></div><div><h3>Statement of significance</h3><div>Currently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 439-448"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378671","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":"Versatile self-assembled near-infrared SERS nanoprobes for multidrug-resistant bacterial infection-specific surveillance and therapy","authors":"Qian Gao ,&nbsp;Ruocan Liu ,&nbsp;Yundi Wu ,&nbsp;Fuxiang Wang ,&nbsp;Xilong Wu","doi":"10.1016/j.actbio.2024.09.054","DOIUrl":"10.1016/j.actbio.2024.09.054","url":null,"abstract":"<div><div>The rise of multidrug-resistant bacteria (MDRB) has made bacterial infection one of the biggest health threats, causing numerous antibiotics to fail. Real-time monitoring of bacterial disease treatment efficacy at the infection site is required. Herein, we report a versatile Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated star-shaped Au-MoS₂@hyaluronic acid (AMD@HA) nanocomposite as a surface-enhanced Raman scattering (SERS) nanoprobe for quick bacterial identification and in-situ eradication. Localized surface plasmon resonance (LSPR) from the hybrid metallic nanostructure makes AMD@HA highly responsive to the near-infrared laser, enabling it to demonstrate a photothermal (PTT) effect, increased SERS activity, and peroxidase-like catalytic reaction to release reactive oxygen species. The tail vein injection of AMD@HA nanoprobes is invasive, however SERS imaging for bacterial identification is non-invasive and sensitive, making it an efficient residual bacteria monitoring method. The detection limit for methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is as low as 10² CFU·mL^-1, and the substrates allow for taking 120 s to acquire a Raman image of 1600 (40 × 40) pixels. In mouse models of MRSA-induced wound infection and skin abscess, the combination of AMD@HA-mediated PTT and catalytic therapy demonstrates a synergistic effect in promoting wound healing through rapid sterilization. This SERS-guided therapeutic approach exhibits little toxicity and does not cause considerable collateral damage, offering a highly promising intervention for treating diseases caused by MDRB.</div></div><div><h3>Statement of significance</h3><div>This research introduces a SERS nanoprobe, AMD@HA, for the rapid identification and eradication of multidrug-resistant bacteria (MDRB), a critical health threat. The nanoprobe leverages localized surface plasmon resonance for photothermal therapy and enhanced Raman signals, offering a sensitive, non-invasive diagnostic tool. With a low detection limit for MRSA and a synergistic therapeutic effect in mouse models, our approach holds significant promise for treating MDRB-driven infections with minimal toxicity, advancing the field of antimicrobial strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 559-573"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382712","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":"Laser powder bed fusion printed poly-ether-ether-ketone/bioactive glass composite scaffolds with dual-scale pores for enhanced osseointegration and bone ingrowth","authors":"Haoze Wang ,&nbsp;Zixing Shu ,&nbsp;Peng Chen ,&nbsp;Jin Su ,&nbsp;Hao Zhu ,&nbsp;Jiawei Jiang ,&nbsp;Chunze Yan ,&nbsp;Jun Xiao ,&nbsp;Yusheng Shi","doi":"10.1016/j.actbio.2024.09.055","DOIUrl":"10.1016/j.actbio.2024.09.055","url":null,"abstract":"<div><div>Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. <em>In vitro</em> assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, <em>in vivo</em> experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt.% and 25 wt.% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds’ effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold.</div></div><div><h3>Statement of significance</h3><div>This study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. <em>In vitro</em> and <em>in vivo</em> analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 605-620"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402217","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":"Tissue expansion mitigates radiation-induced skin fibrosis in a porcine model","authors":"Laura Nunez-Alvarez ,&nbsp;Joanna K. Ledwon ,&nbsp;Sarah Applebaum ,&nbsp;Bianka Progri ,&nbsp;Tianhong Han ,&nbsp;Joel Laudo ,&nbsp;Vahidullah Tac ,&nbsp;Arun K. Gosain ,&nbsp;Adrian Buganza Tepole","doi":"10.1016/j.actbio.2024.09.035","DOIUrl":"10.1016/j.actbio.2024.09.035","url":null,"abstract":"<div><div>Tissue expansion (TE) is the primary method for breast reconstruction after mastectomy. In many cases, mastectomy patients undergo radiation treatment (XR). Radiation is known to induce skin fibrosis and is one of the main causes for complications during post-mastectomy breast reconstruction. TE, on the other hand, induces a pro-regenerative response that culminates in growth of new skin. However, the combined effect of XR and TE on skin mechanics is unknown. Here we used the porcine model of TE to study the effect of radiation on skin fibrosis through biaxial testing, histological analysis, and kinematic analysis of skin deformation over time. We found that XR leads to stiffening of skin compared to control based on a shift in the transition stretch (transition between a low stiffness and an exponential stress-strain region characteristic of collagenous tissue) and an increase in the high modulus (modulus computed with stress-stretch data past the transition point). The change in transition stretch can be explained by thicker, more aligned collagen fiber bundles measured in histology images. Skin subjected to both XR+TE showed similar microstructure to controls as well as similar biaxial response, suggesting that physiological remodeling of collagen induced by TE partially counteracts pro-fibrotic XR effects. Skin growth was indirectly assessed with a kinematic approach that quantified increase in permanent area changes without reduction in thickness, suggesting production of new tissue driven by TE even in the presence of radiation treatment. Future work will focus on the detailed biological mechanisms by which TE counteracts radiation induced fibrosis.</div></div><div><h3>Statement of significance</h3><div>Breast cancer is the most prevalent in women and its treatment often results in total breast removal (mastectomy), followed by reconstruction using tissue expanders. Radiation, which is used in about a third of breast reconstruction cases, can lead to significant complications. The timing of radiation treatment remains controversial. Radiation is known to cause immediate skin damage and long-term fibrosis. Tissue expansion leads to a pro-regenerative response involving collagen remodeling. Here we show that tissue expansion immediately prior to radiation can reduce the level of radiation-induced fibrosis. Thus, we anticipate that this new evidence will open up new avenues of investigation into how the collagen remodeling and pro-regenerative effects of tissue expansion can be leverage to prevent radiation-induced fibrosis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 427-438"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334153","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":"Elucidating the unexpected cell adhesive properties of agarose substrates. The effect of mechanics, fetal bovine serum and specific peptide sequences","authors":"Francesco Piazza ,&nbsp;Beatrice Ravaglia ,&nbsp;Andrea Caporale ,&nbsp;Ana Svetić ,&nbsp;Pietro Parisse ,&nbsp;Fioretta Asaro ,&nbsp;Gabriele Grassi ,&nbsp;Luca Secco ,&nbsp;Riccardo Sgarra ,&nbsp;Eleonora Marsich ,&nbsp;Ivan Donati ,&nbsp;Pasquale Sacco","doi":"10.1016/j.actbio.2024.09.042","DOIUrl":"10.1016/j.actbio.2024.09.042","url":null,"abstract":"<div><div>2D agarose substrates have recently been surprisingly shown to be permissive for cell adhesion, depending on their mechanics and the use of the adhesive proteins of fetal bovine serum (FBS) in the cell culture medium. Here, we elucidate how the cells exhibit two anchoring mechanisms depending on the amount of FBS. Under low FBS conditions, the cells recognize the surface-coupled adhesive sequences of fibronectin via the binding of the heterodimer α₅β₁ integrin. Functionality of the actomyosin axis and mechanoactivation of focal adhesion kinase (FAK) are essential for the stretching of the protein, thereby accessing the “synergy” PPSRN site and enhancing cell adhesion in combination with the downstream RGD motif. Under high FBS conditions, the specific peptide sequences are much less relevant as the adsorbed serum proteins conceal the coupled fibronectin and the cells recognize the adhesive protein vitronectin, which is constitutively present in FBS, via the binding of the heterodimer α_vβ₃ integrin. Similarly, the intracellular tension and FAK activity are decisive, which collectively indicate that the cells stretch the partially cryptic RGD site of vitronectin and thus make it more accessible for integrin binding. Both anchoring mechanisms only work properly if the agarose substrate is mechanically compliant in terms of linear stress-strain response, unraveling a critical balance between the mechanics of the agarose substrate and the presentation of the adhesive peptides.</div></div><div><h3>Statement of significance</h3><div>In the context of biomaterial design, agarose hydrogels are known to lack intrinsic cell-adhesive peptide motifs and are therefore commonly used for the development of non-permissive 2D substrates. However, we unexpectedly found that agarose hydrogels can become permissive substrates for cell adhesion, depending on a compliant mechanical response of the substrate and the use of fetal bovine serum (FBS) as protein reservoir in the cell culture medium. We describe here two anchoring mechanisms that cells harness to adhere to agarose substrates, depending on the amount of FBS. Our results will have a major impact on the field of mechanobiology and shed light on the central role of FBS as a natural source of adhesive proteins that could promote cell anchoring.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 286-297"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367736","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":"Automated model discovery for textile structures: The unique mechanical signature of warp knitted fabrics","authors":"Jeremy A. McCulloch,&nbsp;Ellen Kuhl","doi":"10.1016/j.actbio.2024.09.051","DOIUrl":"10.1016/j.actbio.2024.09.051","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Textile fabrics have unique mechanical properties, which make them ideal candidates for many engineering and medical applications: They are initially flexible, nonlinearly stiffening, and ultra-anisotropic. Various studies have characterized the response of textile structures to mechanical loading; yet, our understanding of their exceptional properties and functions remains incomplete. Here we integrate biaxial testing and constitutive neural networks to automatically discover the best model and parameters to characterize warp knitted polypropylene fabrics. We use experiments from different mounting orientations, and discover interpretable anisotropic models that perform well during both training and testing. Our study shows that constitutive models for warp knitted fabrics are highly sensitive to an accurate representation of the textile microstructure, and that models with three microstructural directions outperform classical orthotropic models with only two in-plane directions. Strikingly, out of 2&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;/mrow&gt;&lt;mn&gt;14&lt;/mn&gt;&lt;/msup&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;16,384 possible combinations of terms, we consistently discover models with two exponential linear fourth invariant terms that inherently capture the initial flexibility of the virgin mesh and the pronounced nonlinear stiffening as the loops of the mesh tighten. We anticipate that the tools we have developed and prototyped here will generalize naturally to other textile fabrics–woven or knitted, weft knit or warp knit, polymeric or metallic–and, ultimately, will enable the robust discovery of anisotropic constitutive models for a wide variety of textile structures. Beyond discovering constitutive models, we envision to exploit automated model discovery as a novel strategy for the generative material design of wearable devices, stretchable electronics, and smart fabrics, as programmable textile metamaterials with tunable properties and functions. Our source code, data, and examples are available at https://github.com/LivingMatterLab/CANN.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Textile structures are rapidly gaining popularity in many biomedical applications including tissue engineering, wound healing, and surgical repair. A precise understanding of their unique mechanical properties is critical to tailor them to their specific functions. Here we integrate mechanical testing and machine learning to automatically discover the best models for knitted polypropylene fabrics. We show that warp knitted fabrics possess a complex symmetry with three distinct microstructural directions. Along these, the behavior is dominated by an exponential linear term that characterize the initial flexibility of the virgin mesh and the nonlinear stiffening as the loops of the fabric tighten. We expect that our technology will generalize naturally to other fabrics and enable the robust discovery of complex anisotropic models for a wide variety of textile structures.","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 461-477"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378672","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":"A biodegradable Fe–0.6Se alloy with superior strength and effective antibacterial and antitumor capabilities for orthopedic applications","authors":"Bo Deng ,&nbsp;Dechuang Zhang ,&nbsp;Yilong Dai ,&nbsp;Sihan Lin ,&nbsp;Yuncang Li ,&nbsp;Cuie Wen","doi":"10.1016/j.actbio.2024.10.012","DOIUrl":"10.1016/j.actbio.2024.10.012","url":null,"abstract":"<div><div>Iron–selenium (Fe–Se) alloys have potential as attractive biodegradable bone–implant materials, given the antitumor properties of Se in cancer prevention and therapy. However, the fabrication of Fe–Se alloys is challenging due to the volatility of elemental Se and the significantly different melting points of Se and Fe. In this study, we successfully fabricated Fe–xSe (<em>x</em> = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys using suction casting, with FeSe compounds as the Se source. The microstructures, tensile properties, corrosion behavior, biocompatibility, antibacterial ability, and antitumor properties of the Fe–Se alloys were evaluated. The microstructures of the Fe–Se alloys were composed of α–Fe and FeSe phases. Among the Fe–Se alloys, Fe–0.6Se showed the best combination of tensile properties, with a yield strength of 1096.5 ± 7.2 MPa, an ultimate tensile strength of 1271.6 ± 6.3 MPa, and a fracture strain of 15.6 ± 3.3 %, and a degradation rate of 56.9 ± 0.4 μm/year. Moreover, the Fe–0.6Se alloy showed superb antibacterial ability against <em>S. aureus</em>, antitumor activity against 143B osteosarcoma cells, and osteogenicity and biocompatibility toward pre–osteoblast MC3T3–E1 cells. In summary, adding 0.2–1.0 wt.% Se to Fe does not affect the growth of healthy cells but effectively inhibits the growth and reproduction of tumor cells, and the Fe–0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties.</div></div><div><h3>Statement of significance</h3><div>This work reports on Fe-xSe (<em>x</em> = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys fabricated using suction casting. The microstructures of the Fe–Se alloys were composed of α-Fe and FeSe phases. Among the Fe–Se alloys, the Fe-0.6Se showed the best combination of tensile properties, with a yield strength of 1058.6 ± 3.9 MPa, an ultimate tensile strength of 1134.1 ± 2.9 MPa, and a fracture strain of 16.8 ± 1.5 %, and a degradation rate of 56.9 ± 0.4 μm/year. Moreover, the Fe-0.6Se alloy showed superb antibacterial ability against <em>S. aureus</em>, antitumor activity against 143B osteosarcoma cells, and significant osteogenic ability and biocompatibility toward pre-osteoblast MC3T3-E1 cells. In summary, the Fe-0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 633-650"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482752","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":"A multifunctional self-reinforced injectable hydrogel for enhancing repair of infected bone defects by simultaneously targeting macrophages, bacteria, and bone marrow stromal cells","authors":"Jingyi Du ,&nbsp;Ying Chu ,&nbsp;Yan Hu ,&nbsp;Jin Liu ,&nbsp;Hanghang Liu ,&nbsp;Huimin Wang ,&nbsp;Changying Yang ,&nbsp;Zheng Wang ,&nbsp;Aixi Yu ,&nbsp;Jiabing Ran","doi":"10.1016/j.actbio.2024.10.014","DOIUrl":"10.1016/j.actbio.2024.10.014","url":null,"abstract":"<div><div>Injectable hydrogels (IHs) have demonstrated huge potential in promoting repair of infected bone defects (IBDs), but how to endow them with desired anti-bacterial, immunoregulatory, and osteo-inductive properties as well as avoid mechanical failure during their manipulation are challenging. In this regard, we developed a multifunctional AOHA-RA/Lap nanocomposite IH for IBDs repair, which was constructed mainly through two kinds of reversible cross-links: (i) the laponite (Lap) crystals mediated electrostatic interactions; (ii) the phenylboronic acid easter bonds between the 4-aminobenzeneboronic acid grafted oxidized hyaluronic acid (AOHA) and rosmarinic acid (RA). Due to the specific structural composition, the AOHA-RA/Lap IH demonstrated superior injectability, self-recoverability, spatial adaptation, and self-reinforced mechanical properties after being injected to the bone defect site. In addition, the RA molecules could be locally released from the hydrogel following a Weibull model for over 10 days. Systematic <em>in vitro/vivo</em> assays proved the strong anti-bacterial activity of the hydrogel against <em>Staphylococcus aureus</em> (<em>S. aureu</em>s) and <em>Escherichia coli</em> (<em>E. coli</em>). Moreover, its capability of inducing M₂ polarization of macrophages (M_φ) and osteogenic differentiation of bone marrow stromal cells (BMSCs) was verified either, and the mechanism of the former was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways and that of the latter was identified to be related to the calcium signaling pathway, extracellular matrix (ECM) receptor interaction and TGF-β signaling pathway. After being implanted to a <em>S. aureus</em> infected rat skull defect model, the AOHA-RA/Lap IH significantly accelerated repair of IBDs without causing significant systemic toxicity.</div></div><div><h3>Statement of significance</h3><div>Rosmarinic acid and laponite were utilized to develop an injectable hydrogel, promising for accelerating repair of infected bone defects in clinic. The gelation of the hydrogel was completely driven by two kinds of reversible cross-links, which endow the hydrogel superior spatial adaption, self-recoverability, and structural stability. The as-prepared hydrogel demonstrated superior anti-bacterial/anti-biofilm activity and could induce M₂ polarization of macrophages and osteogenic differentiation of BMSCs. The mechanism behind macrophages polarization was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways. The mechanism behind osteogenic differentiation of BMSCs was identified to be related to the ECM receptor interaction and calcium signaling/TGF-β signaling pathways.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 232-253"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482755","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 immunostimulatory CD73 antibody-polymeric cytotoxic drug complex for triple negative breast cancer therapy","authors":"Xiao Xie ,&nbsp;Ming Yang ,&nbsp;Xue Wei ,&nbsp;Hongyu Chu ,&nbsp;Weidong Zhao ,&nbsp;Na Shen","doi":"10.1016/j.actbio.2024.09.033","DOIUrl":"10.1016/j.actbio.2024.09.033","url":null,"abstract":"<div><div>Treatment of triple-negative breast cancer (TNBC) poses significant challenges due to its propensity for metastasis. A key impediment lies in the suppressive immune microenvironment, which fosters tumor progression. This study introduces an approach employing a dual immune-stimulatory CD73 antibody-polymeric cytotoxic drug complex (αCD73-PLG-MMAE). This complex is designed for targeted eradication of TNBC while modulating tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. By enhancing antitumor immune responses, this strategy offers a highly effective means of treating TNBC and mitigating metastasis. The complex is synthesized by combining αCD73 with poly(_L-glutamic acid) (PLG) grafted Fc binding peptides (Fc-III-4C) and Val-Cit-PAB-monomethyl auristatin E (MMAE), exploiting the affinity between αCD73 and Fc-III-4C. αCD73 selectively targets CD73 molecules on both tumor and immune suppressive cells, thereby inhibiting the adenosine pathway. Meanwhile, Val-Cit-PAB-MMAE, activated by cathepsin B, triggers selective release of MMAE, inducing ICD in tumor cells. In a 4T1 tumor model, αCD73-PLG-MMAE significantly enhances drug accumulation in tumors by 4.13-fold compared to IgG-PLG-MMAE, leading to suppression of tumor growth and metastasis. Furthermore, it synergistically augments the antitumor effects of αPD-1, resulting in a tumor inhibition rate of 92 % as compared to 21 % with αPD-1 alone. This study thus presents a pioneering therapeutic strategy for TNBC, emphasizing the potential of targeted immunomodulation in cancer treatment.</div></div><div><h3>Statement of significance</h3><div>Antibody-drug conjugate (ADC) therapy holds promise for treating triple-negative breast cancer (TNBC). However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this \"cold tumor\". Here, we present a dual immune-stimulatory complex, αCD73-PLG-MMAE, which targets TNBC specifically and modulates tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 532-544"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334137","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}