Acta Biomaterialia最新文献

{"title":"Adoptive transfer of immunomodulatory macrophages reduces the pro-inflammatory microenvironment and increases bone formation on titanium implants","authors":"Lais Morandini ,&nbsp;Tyler Heath ,&nbsp;Luke S. Sheakley ,&nbsp;Derek Avery ,&nbsp;Melissa Grabiec ,&nbsp;Michael Friedman ,&nbsp;Rebecca K. Martin ,&nbsp;Jonathan Boyd ,&nbsp;Rene Olivares-Navarrete","doi":"10.1016/j.actbio.2024.09.011","DOIUrl":"10.1016/j.actbio.2024.09.011","url":null,"abstract":"<div><div>Macrophages play a central role in orchestrating the inflammatory response to implanted biomaterials and are sensitive to changes in the chemical and physical characteristics of the implant. Macrophages respond to biological, chemical, and physical cues by polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) states. We previously showed that rough-hydrophilic titanium (Ti) implants skew macrophage polarization towards an anti-inflammatory phenotype and increase mesenchymal stem cell (MSC) recruitment and bone formation around the implant. In the present study, we aimed to investigate whether the adoptive transfer of macrophages in different polarization states would alter the inflammatory microenvironment and improve biomaterial integration in macrophage-competent and macrophage-ablated mice. We found that ablating macrophages increased the presence of neutrophils, reduced T cells and MSCs, and compromised the healing and biomaterial integration process. These effects could not be rescued with adoptive transfer of naïve or polarized macrophages. Adoptive transfer of M1 macrophages into macrophage-competent mice increased inflammatory cells and inflammatory microenvironment, resulting in decreased bone-to-implant contact. Adoptive transfer of M2 macrophages into macrophage-competent mice reduced the pro-inflammatory environment in the peri‑implant tissue and increased bone-to-implant contact. Taken together, our results show the importance of macrophages in controlling and modulating the inflammatory process in response to implanted biomaterials and suggest they can be used to improve outcomes following biomaterial implantation.</div></div><div><h3>Statement of significance</h3><div>Macrophages are central in orchestrating the inflammatory response to implanted biomaterials and are sensitive to biomaterial chemical and physical characteristics. Our study shows that a deficiency of macrophages results in prolonged inflammation and abolishes bone-biomaterial integration. Adoptive transfer of immunomodulatory macrophages into macrophage-competent mice reduced the inflammatory environment and increased bone-implant contact.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 432-445"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303125","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":"Hagfish-inspired hydrogel for root caries: A multifunctional approach including immediate protection, antimicrobial phototherapy, and remineralization","authors":"Jieyu Zhu ,&nbsp;Min Zhang ,&nbsp;Rongmin Qiu ,&nbsp;Moyan Li ,&nbsp;Li Zhen ,&nbsp;Jiyao Li ,&nbsp;Jun Luo ,&nbsp;Jianshu Li ,&nbsp;Hongkun Wu ,&nbsp;Jiaojiao Yang","doi":"10.1016/j.actbio.2024.09.014","DOIUrl":"10.1016/j.actbio.2024.09.014","url":null,"abstract":"<div><div>Root caries is the main cause of oral pain and tooth loss in the elderly. Protecting root lesions from environmental disturbances, resisting pathogens, and facilitating remineralization over time are essential for addressing root caries, but are challenging due to the irregular root surface and the complex oral environment. Hagfish secretes slime when facing danger, which converts into gels upon contact with seawater, suffocating the predators. Inspired by hagfish's defense mechanism, a fluid-hydrogel conversion strategy is proposed to establish a mechanical self-regulating multifunctional platform for root caries treatment. The fluid system (silk fibroin-tannic acid-black phosphorene-urea, ST-BP-U), in which urea disrupts the hydrogen bonds between silk fibroin and tannic acid, can easily spread on the irregular root surface and permeate into dentinal tubules. Upon contact with the surrounding water, urea diffuses, prompting the hydrogel re-formation and creating intimate attachments with micromechanical inlay locks. Meanwhile, BP increases the crosslinking of the re-formed hydrogel network, resulting in reinforced cohesion for robust wet adhesion to the tooth root. This process establishes a structured platform for effective antimicrobial phototherapy and dentin remineralization promotion. This water-responsive fluid-hydrogel conversion system adapts to the irregular root surface in the dynamic wet environment, holding promise for addressing root caries.</div></div><div><h3>Statement of significance</h3><div>Root caries bring a heavy burden to the aging society, but the irregular root surface and dynamic moist oral environment always hinder non-surgical therapeutic effects. Here, we propose a water-responsive fluid-hydrogel conversion strategy aimed at mechanical self-regulation on the irregular and wet root interface to construct a functional structural platform. The liquid system (ST-BP-U) that prebreak intermolecular hydrogen bonds can easily spread on irregular surfaces and dentin tubules. When encountering water, hydrogen bonds re-form, and BP increases the crosslinking of the hydrogel formed <em>in situ</em>. Based on this firm wet-adhesion platform, it provides powerful phototherapy effects and promotes dentin remineralization. This fluid-hydrogel conversion system turns the disadvantages of wet environment into advantages, offering a promising strategy for root caries.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 117-137"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303131","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":"Latent stem cell-stimulating radially aligned electrospun nanofibrous patches for chronic tympanic membrane perforation therapy","authors":"Juo Lee ,&nbsp;Sangbae Park ,&nbsp;Beomyong Shin ,&nbsp;Yeon Ju Kim ,&nbsp;Sungmin Lee ,&nbsp;Jungsil Kim ,&nbsp;Kyoung-Je Jang ,&nbsp;Oak-Sung Choo ,&nbsp;Jangho Kim ,&nbsp;Hoon Seonwoo ,&nbsp;Jong Hoon Chung ,&nbsp;Yun-Hoon Choung","doi":"10.1016/j.actbio.2024.09.019","DOIUrl":"10.1016/j.actbio.2024.09.019","url":null,"abstract":"<div><div>Chronic tympanic membrane (TM) perforation is a tubotympanic disease caused by either traumatic injury or inflammation. A recent study demonstrated significant progress in promoting the regeneration of chronic TM perforations through the application of nanofibers with radially aligned nanostructures and controlled release of growth factors. However, radially aligned nanostructures with stem cell-stimulating factors have never been used. In this study, insulin-like growth factor binding factor 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. The IRA-NFPs were prepared by electrospinning 8 wt% polycaprolactone in trifluoroethanol and acetic acid (9:1). Random nanofibers (RFs) and aligned nanofibers (AFs) were successfully fabricated using a flat plate and a custom-designed circular collector, respectively. The presence of IGFBP2 was confirmed via Fourier transform infrared spectroscopy and the release of IGFBP2 was sustained for up to 20 days. <em>In vitro</em> studies revealed enhanced cellular proliferation and migration on AFs compared to RFs, and the incorporation of IGFBP2 further promoted these effects. Quantitative real-time PCR revealed mRNA downregulation, correlating with accelerated migration and increased cell confluency. <em>In vivo</em> studies showed IGFBP2-loaded RF and AF patches increased regeneration success rates by 1.59-fold and 2.23-fold, respectively, while also reducing healing time by 2.5-fold compared to the control. Furthermore, IGFBP2-incorporated AFs demonstrated superior efficacy in healing larger perforations with enhanced histological similarity to native TMs. This study, combining stem cell stimulating factors and aligned nanostructures, proposes a novel approach potentially replacing conventional surgical methods for chronic TM perforation regeneration.</div></div><div><h3>Statement of significance</h3><div>Chronic otitis media (COM) affects approximately 200 million people worldwide due to inflammation, inadequate blood supply, and lack of growth factors. Current surgical treatments have limitations like high costs and anesthetic risks. Recent research explored the use of nanofibers with radially aligned nanostructures and controlled release of growth factors to treat chronic tympanic membrane (TM) perforations. In this study, insulin-like growth factor binding protein 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. We assessed their properties and efficacy through <em>in vitro</em> and <em>in vivo</em> studies. IRA-NFPs showed promising healing capabilities with chronic TM perforation models. This innovative approach has the potential to improve COM management, reduce surgery costs, and enhance patient safety.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 212-222"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303134","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":"Microneedle transdermal drug delivery as a candidate for the treatment of gouty arthritis: Material structure, design strategies and prospects","authors":"Hong Yi ,&nbsp;Haojie Yu ,&nbsp;Li Wang ,&nbsp;Yu Wang ,&nbsp;Chenguang Ouyang ,&nbsp;Basem E. Keshta","doi":"10.1016/j.actbio.2024.08.032","DOIUrl":"10.1016/j.actbio.2024.08.032","url":null,"abstract":"<div><div>Gouty arthritis (GA) is caused by monosodium urate (MSU) crystals deposition. GA is difficult to cure because of its complex disease mechanism and the tendency to reoccur. GA patients require long-term uric acid-lowering and anti-inflammatory treatments. In the past ten years, as a painless, convenient and well-tolerated new drug transdermal delivery method, microneedles (MNs) administration has been continuously developed, which can realize various drug release modes to deal with various complex diseases. Compared with the traditional administration methods (oral and injection), MNs are more conducive to the long-term independent treatment of GA patients because of their safe, efficient and controllable drug delivery ability. In this review, the pathological mechanism of GA and common therapeutic drugs for GA are summarized. After that, MNs drug delivery mechanisms were summarized: dissolution release mechanism, swelling release mechanism and channel-assisted release mechanism. According to drug delivery patterns of MNs, the mechanisms and applications of rapid-release MNs, long-acting MNs, intelligent-release MNs and multiple-release MNs were reviewed. Additionally, existing problems and future trends of MNs in the treatment of GA were also discussed.</div></div><div><h3>Statement of significance</h3><div>Gout is an arthritis caused by metabolic disease \"hyperuricemia\". Epidemiological studies show that the number of gouty patients is increasing rapidly worldwide. Due to the complex disease mechanism and recurrent nature of gout, gouty patients require long-term therapy. However, traditional drug delivery modes (oral and injectable) have poor adherence, low drug utilization, and lack of local localized targeting. They may lead to adverse effects such as rashes and gastrointestinal reactions. As a painless, convenient and well-tolerated new drug transdermal delivery method, microneedles have been continuously developed, which can realize various drug release modes to deal with gouty arthritis. In this review, the material structure, design strategy and future outlook of microneedles for treating gouty arthritis will be reviewed.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 20-50"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057487","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":"Pancreatic islet cells in microfluidic-spun hydrogel microfibers for the treatment of diabetes","authors":"Zhikun Huan ,&nbsp;Jingbo Li ,&nbsp;Jiahui Guo ,&nbsp;Yunru Yu ,&nbsp;Ling Li","doi":"10.1016/j.actbio.2024.08.047","DOIUrl":"10.1016/j.actbio.2024.08.047","url":null,"abstract":"<div><div>Islet transplantation has been developed as an effective cell therapy strategy to treat the progressive life-threatening disease Type 1 diabetes (T1DM). To mimic the natural islets and achieve immune isolation, hydrogel encapsulation of multiple islet cell types is the current endeavor. Here, we present a microfiber loading with pancreatic α and β cells by microfluidic spinning for diabetes treatment. Benefiting from microfluidic technology, the cells could be controllably and continuously loaded in the alginate and methacrylated hyaluronic acid (Alg-HAMA) microfiber and maintained their high bioactivity. The resultant microfiber could then hold the capacity of dual-mode glucose responsiveness attributed to the glucagon and insulin secreted by the encapsulated pancreatic α and β cells. After transplantation into the brown adipose tissue (BAT), these cell-laden microfibers showed successful blood glucose control in rodents and avoided the occurrence of hypoglycemia. These results conceived that the multicellular microfibers are expected to provide new insight into artificial islet preparation, diabetes treatment, and regenerative medicine as well as tissue engineering.</div></div><div><h3>Statement of significance</h3><div><ul><li><span>•</span><span><div>The microfibers were generated with a double network of alginate and methacrylated hyaluronic acid.</div></span></li><li><span>•</span><span><div>The microfibers could simultaneously encapsulate pancreatic α and β cells and showed dual-mode glucose responsiveness.</div></span></li><li><span>•</span><span><div>The cell-laden microfibers maintained a long-term hormone-releasing function <em>in vivo</em>.</div></span></li><li><span>•</span><span><div>Cell-laden microfibers transplanted into diabetic mice could achieve glycemic control for 6 weeks.</div></span></li></ul></div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 149-160"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121305","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 fibroblast activation protein α-activatable nanoagent co-delivering diethyldithiocarbamate and copper for tumor therapy and imaging","authors":"Yaqing Ding ,&nbsp;Zeqian Huang ,&nbsp;Yong Luo,&nbsp;Huanxin Lin,&nbsp;Jue Wang,&nbsp;Zishan Zeng,&nbsp;Tao Zhang,&nbsp;Yiwei Chen,&nbsp;Yujun Gong,&nbsp;Mingxia Zhang,&nbsp;Chunshun Zhao","doi":"10.1016/j.actbio.2024.08.009","DOIUrl":"10.1016/j.actbio.2024.08.009","url":null,"abstract":"<div><div>Disulfiram (DSF), an FDA-approved drug for treating alcoholism, has been verified with Cu²⁺-dependent anticancer activity by forming Cu(DTC)₂, the complex of one of its metabolites diethyldithiocarbamate (DTC) and Cu²⁺. Nevertheless, the antitumor effect is limited by insufficient Cu(DTC)₂ formation <em>in suit</em> and off-target system toxicity. Herein, we developed a fibroblast activation protein α (FAPα) activatable nanoagent (HfD-HID-Cu) for co-delivery of DTC polymeric prodrug and exogenous Cu²⁺ to achieve enhanced cancer-specific therapy and activatable <em>in situ</em> fluorescence imaging meanwhile. HfD-HID-Cu was simply constructed through the co-assembly of the DTC polymeric prodrug (HA-fap-DTC) and the copper-loaded IR808-conjugated polymer (HA-IR-DPA-Cu), which could serve as the “OFF-to-ON” switch for chemotherapy and fluorescence. With the high expression of FAPα in tumor tissues, HA-fap-DTC could be activated specifically to release DTC, while maintaining inactive in normal tissues. The liberated DTC within tumor tissues could contend for Cu²⁺ from HA-IR-DPA-Cu, resulting in the formation of highly cytotoxic Cu(DTC)₂ <em>in situ</em> for chemotherapy, concomitant with the fluorescence recovery of cyanine dye for tumor imaging. This work provides an effective strategy for co-delivery of DTC prodrug and Cu²⁺ for tumor theranostic with improved selectivity and minimal side effects.</div></div><div><h3>Statement of significance</h3><div>DSF-based antitumor therapy is highly dependent on Cu²⁺. However, the non-synchronous distribution of DSF/DTC and Cu²⁺ in tumor tissues attenuates the antitumor efficacy. The insufficient Cu(DTC)₂ formation <em>in suit</em> and off-target distribution greatly limit the anti-tumor application. This study provides a nanoagent for co-delivery of DTC polymeric prodrug and Cu²⁺ by simple co-assembly to achieve their synchronous tumor distribution. It can be selectively activated by FAPα, forming cytotoxic Cu(DTC)₂ <em>in suit</em> for tumor-specific chemotherapy and reducing the systemic toxicity. In addition to chemotherapy, the nanoagent can emit fluorescence under the sequential triggering of FAPα and released DTC for tumor imaging. Overall, this study renders a promising strategy for improved Cu(DTC)₂-based antitumor therapy and imaging.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 316-327"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997054","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":"Bone cells influence the degradation interface of pure Mg and WE43 materials: Insights from multimodal in vitro analysis","authors":"Diana C. Martinez ,&nbsp;Anke Borkam-Schuster ,&nbsp;Heike Helmholz ,&nbsp;Anna Dobkowska ,&nbsp;Bérengère Luthringer-Feyerabend ,&nbsp;Tomasz Płociński ,&nbsp;Regine Willumeit-Römer ,&nbsp;Wojciech Święszkowski","doi":"10.1016/j.actbio.2024.08.015","DOIUrl":"10.1016/j.actbio.2024.08.015","url":null,"abstract":"<div><div>In this study, the interaction of pure Mg and WE43 alloy under the presence of osteoblast (OB) and osteoclast (OC) cells and their influence on the degradation of materials have been deeply analyzed. Since OB and OC interaction has an important role in bone remodeling, we examined the surface morphology and dynamic changes in the chemical composition and thickness of the corrosion layers formed on pure Mg and WE43 alloy by direct monoculture and coculture of pre-differentiated OB and OC cells <em>in vitro</em>. Electrochemical techniques examined the corrosion performance. The corrosion products were characterized using a combination of the focused ion beam (FIB), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Cell viability and morphology were assessed by fluorescent microscopy and SEM. Our findings demonstrate cell spread and attachment variations, which differ depending on the Mg substrates. It was clearly shown that cell culture groups delayed degradation processes with the lowest corrosion rate observed in the presence of OBOC coculture for the WE43 substrate. Ca-P enrichment was observed in the outer-middle region of the corrosion layer but only after 7 days of OBOC coculture on WE43 and after 14 days on the pure Mg specimens.</div></div><div><h3>Statement of significance</h3><div>Magnesium metallic materials that can degrade over time provide distinct opportunities for orthopedic application. However, there is still a lack, especially in elucidating cell-material interface characterization. This study investigated the influence of osteoblast-osteoclast coculture in direct Mg-material contact. Our findings demonstrated that pre-differentiated osteoblasts and osteoclasts cocultured on Mg substrates influenced the chemistry of the corrosion layers. The cell spread and attachment were Mg substrate-dependent. The findings of coculturing bone cells directly on Mg materials within an <em>in vitro</em> model provide an effective approach for studying the dynamic degradation processes of Mg alloys while also elucidating cell behavior and their potential contribution to the degradation of these alloys.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 471-490"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019824","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":"Multiphoton excited polymerized biomimetic models of collagen fiber morphology to study single cell and collective migration dynamics in pancreatic cancer","authors":"Sophie Mancha ,&nbsp;Meghan Horan ,&nbsp;Ojaswi Pasachhe ,&nbsp;Adib Keikhosravi ,&nbsp;Kevin W. Eliceiri ,&nbsp;Kristina A. Matkowskyj ,&nbsp;Jacob Notbohm ,&nbsp;Melissa C. Skala ,&nbsp;Paul J. Campagnola","doi":"10.1016/j.actbio.2024.08.026","DOIUrl":"10.1016/j.actbio.2024.08.026","url":null,"abstract":"<div><div>The respective roles of aligned collagen fiber morphology found in the extracellular matrix (ECM) of pancreatic cancer patients and cellular migration dynamics have been gaining attention because of their connection with increased aggressive phenotypes and poor prognosis. To better understand how collagen fiber morphology influences cell-matrix interactions associated with metastasis, we used Second Harmonic Generation (SHG) images from patient biopsies with Pancreatic ductal adenocarcinoma (PDAC) as models to fabricate collagen scaffolds to investigate processes associated with motility. Using the PDAC BxPC-3 metastatic cell line, we investigated single and collective cell dynamics on scaffolds of varying collagen alignment. Collective or clustered cells grown on the scaffolds with the highest collagen fiber alignment had increased E-cadherin expression and larger focal adhesion sites compared to single cells, consistent with metastatic behavior. Analysis of single cell motility revealed that the dynamics were characterized by random walk on all substrates. However, examining collective motility over different time points showed that the migration was super-diffusive and enhanced on highly aligned fibers, whereas it was hindered and sub-diffusive on un-patterned substrates. This was further supported by the more elongated morphology observed in collectively migrating cells on aligned collagen fibers. Overall, this approach allows the decoupling of single and collective cell behavior as a function of collagen alignment and shows the relative importance of collective cell behavior as well as fiber morphology in PDAC metastasis. We suggest these scaffolds can be used for further investigations of PDAC cell biology.</div></div><div><h3>Statement of significance</h3><div>Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, where aligned collagen has been associated with poor prognosis. Biomimetic models representing this architecture are needed to understand complex cellular interactions. The SHG image-based models based on stromal collagen from human biopsies afford the measurements of cell morphology, cadherin and focal adhesion expression as well as detailed motility dynamics. Using a metastatic cell line, we decoupled the roles of single cell and collective cell behavior as well as that arising from aligned collagen. Our data suggests that metastatic characteristics are enhanced by increased collagen alignment and that collective cell behavior is more relevant to metastatic processes. These scaffolds provide new insight in this disease and can be a platform for further experiments such as testing drug efficacy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 212-226"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057488","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":"Electrospun polycaprolactone-chitosan nanofibers on a zinc mesh as biodegradable guided bone-regeneration membranes with enhanced mechanical, antibacterial, and osteogenic properties for alveolar bone-repair applications","authors":"Wenjie Xu ,&nbsp;Xue Gao ,&nbsp;Menghan Zhang ,&nbsp;Zhengting Jiang ,&nbsp;Xiaomin Xu ,&nbsp;Liangfu Huang ,&nbsp;Huiyu Yao ,&nbsp;Yitian Zhang ,&nbsp;Xian Tong ,&nbsp;Yuncang Li ,&nbsp;Jixing Lin ,&nbsp;Cuie Wen ,&nbsp;Xi Ding","doi":"10.1016/j.actbio.2024.08.033","DOIUrl":"10.1016/j.actbio.2024.08.033","url":null,"abstract":"<div><div>Guided bone-regeneration membrane (GBRM) is commonly used in bone-repair surgery because it blocks fibroblast proliferation and provides spatial support in bone-defect spaces. However, the need for removal surgery and the lack of antibacterial properties of conventional GBRM limit its therapeutic applicability for alveolar bone defects. Here we developed a GBRM for alveolar bone-repair and -regeneration applications through double-sided electrospinning of polycaprolactone and chitosan layers on a Zn mesh surface (denoted DSZM). The DSZM showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times higher than that of commercial Bio-Gide membrane. The DSZM exhibited a corrosion rate of ∼17 µm/y and a Zn ion concentration of ∼0.23 µg/ml after 1 month of immersion in Hanks’ solution. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against <em>S. aureus</em> and osteogenesis in a rat critical-sized maxillary defect model. Overall, the DSZM fits the requirements for alveolar bone-repair and -regeneration applications as a biodegradable GBRM material due to its spatial support, suitable degradability, cytocompatibility, and antibacterial and osteogenic capabilities.</div></div><div><h3>Statement of significance</h3><div>This work reports the mechanical properties, antibacterial ability and osteogenic properties of electrospun PCL-CS nanofiber on Zn mesh as biodegradable guided bone-regeneration membrane for alveolar bone-repair applications. Our findings demonstrate that the DSZM prepared by double-sided electrospinning of PCL-CS layers on Zn mesh showed a UTS of ∼25.6 MPa, elongation of ∼16.1%, strength-elongation product of ∼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times greater than that of commercial Bio-Gide® membrane. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against <em>S. aureus</em> and osteogenesis in a rat critical-sized maxillary defect model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 434-450"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094284","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":"NIR-II triggered Cu(I) phosphide for chemodynamic and photothermal periodontitis treatment: Efficient reduction of bacterial co-aggregation","authors":"Jinying Lin ,&nbsp;Jiao Fang ,&nbsp;Jing Zhou ,&nbsp;Manlin Qi ,&nbsp;Yujia Shi ,&nbsp;Chunyan Li ,&nbsp;Xiaolin Sun ,&nbsp;Biao Dong ,&nbsp;Lin Wang","doi":"10.1016/j.actbio.2024.08.013","DOIUrl":"10.1016/j.actbio.2024.08.013","url":null,"abstract":"<div><div>The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H₂O₂ levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu₃P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting •OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate—a metabolite in periodontal biofilm—into H₂O₂, further amplifying CDT's potential. <em>In vitro</em> Cu₃P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu₃P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue <em>in vivo</em> periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified <em>via</em> the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care.</div></div><div><h3>Statement of significance</h3><div>The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H₂O₂ level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu₃P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu₃P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"187 ","pages":"Pages 396-408"},"PeriodicalIF":9.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019826","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}