Acta Biomaterialia最新文献

{"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}

{"title":"A biphasic drug-releasing microneedle with ROS scavenging and angiogenesis for the treatment of diabetic ulcers","authors":"Xinyue He ,&nbsp;Lianghong Peng ,&nbsp;Liming Zhou ,&nbsp;Huiling Liu ,&nbsp;Yifan Hao ,&nbsp;Yuhan Li ,&nbsp;Zijin lv ,&nbsp;Baohui Zeng ,&nbsp;Xinmin Guo ,&nbsp;Rui Guo","doi":"10.1016/j.actbio.2024.09.045","DOIUrl":"10.1016/j.actbio.2024.09.045","url":null,"abstract":"<div><div>Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. <em>In vitro</em> and <em>in vivo</em> studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers.</div></div><div><h3>Statement of significance</h3><div>In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 270-285"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373746","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":"Multi-functional nanosonosensitizer-engineered bacteria to overcome tumor hypoxia for enhanced sonodynamic therapy","authors":"Ting Wang ,&nbsp;Meng Du ,&nbsp;Zhen Yuan ,&nbsp;Jintong Guo ,&nbsp;Zhiyi Chen","doi":"10.1016/j.actbio.2024.10.013","DOIUrl":"10.1016/j.actbio.2024.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Ultrasound-triggered sonodynamic therapy (SDT), with high safety and acceptance, has become a promising tumor treatment. However, the dense stroma, hypoxic microenvironment of tumor, and the unpredictable treatment timing limit the effectiveness of sonosensitizers and the antitumor therapeutic effect. Thus, it is crucial to develop an imaging-guided sensitization strategy for hypoxic tumor sonosensitization to improve the efficacy of SDT.</div></div><div><h3>Methods</h3><div>In this study, we developed a biohybrid system CB@HPP, which genetically engineered bacteria to express catalase (CB) and modified nanosonosensitizers (HPP) to the surface of these bacteria. Tumor hypoxia relief, tumor targeting, biocompatibility, and antitumor efficacy were evaluated through <em>in vitro</em> and <em>in vivo</em> experiments. In addition, the photoacoustic (PA), ultrasound (US), and fluorescence (FL) imaging effects of CB@HPP were evaluated <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>After intravenous injection, CB@HPP was able to target tumor tissue. CB@HPP possessed efficient catalase activity and successfully degraded hydrogen peroxide to produce oxygen. Increased oxygen levels relief intratumoral hypoxia, thereby enhancing CB@HPP-mediated. In addition, CB@HPP showed FL/PA/US multimodal imaging capabilities, which reflects the aggregation effect of CB@HPP in the tumor and suggest the timing of treatment.</div></div><div><h3>Conclusion</h3><div>The biohybrid system CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.</div></div><div><h3>Statement of significance</h3><div>This study developed a sensitizing SDT strategy for imaging-guided drug-targeted delivery and <em>in situ</em> oxygen production. We designed a biohybrid system CB@HPP, which was hybridized by the engineered bacteria with catalytic oxygen production and nanosonosensitizer with multimodal imaging capability. CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 519-531"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482766","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":"Deciphering the complex mechanics of atherosclerotic plaques: A hybrid hierarchical theory-microrheology approach","authors":"Zhuo Chang ,&nbsp;Yidan Zhou ,&nbsp;Le Dong ,&nbsp;Lin-Ru Qiao ,&nbsp;Hui Yang ,&nbsp;Guang-Kui Xu","doi":"10.1016/j.actbio.2024.09.029","DOIUrl":"10.1016/j.actbio.2024.09.029","url":null,"abstract":"<div><div>Understanding the viscoelastic properties of atherosclerotic plaques at rupture-prone scales is crucial for assessing their vulnerability. Here, we develop a Hybrid Hierarchical theory-Microrheology (HHM) approach, enabling the analysis of multiscale mechanical variations and distribution changes in regional tissue viscoelasticity within plaques across different spatial scales. We disclose a universal two-stage power-law rheology in plaques, characterized by distinct power-law exponents (<em>α</em>_short and <em>α</em>_long), which serve as mechanical indexes for plaque components and assessing mechanical gradients. We further propose a self-similar hierarchical theory that effectively delineates plaque heterogeneity from the cytoplasm, cell, to tissue levels. Moreover, our proposed multi-layer perceptron model addresses the viscoelastic heterogeneity and gradients within plaques, offering a promising diagnostic strategy for identifying unstable plaques. These findings not only advance our understanding of plaque mechanics but also pave the way for innovative diagnostic approaches in cardiovascular disease management.</div></div><div><h3>Statement of significance</h3><div>Our study pioneers a Hybrid Hierarchical theory-Microrheology (HHM) approach to dissect the intricate viscoelasticity of atherosclerotic plaques, focusing on distinct components including cap fibrosis, lipid pools, and intimal fibrosis. We unveil a universal two-stage power-law rheology capturing mechanical variations across plaque structures. The proposed hierarchical model adeptly captures viscoelasticity changes from cytoplasm, cell to tissue levels. Based on the newly proposed markers, we further develop a machine learning (ML) diagnostic model that sets precise criteria for evaluating plaque components and heterogeneity. This work not only reveals the comprehensive mechanical heterogeneity within plaques but also introduces a mechanical marker-based ML strategy for assessing plaque conditions, offering a significant leap towards understanding and diagnosing atherosclerotic risks.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 399-412"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303128","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}