Acta biomaterialia最新文献

{"title":"Coaxial printing of slow-release heparin-binding epidermal growth factor scaffold to avoid the occurrence of intrauterine adhesions.","authors":"Jing He, Zeming Gu, Qianqian Wei, Jing Zhang, Yuan Sun, Huifeng Shao, Yong He","doi":"10.1016/j.actbio.2025.06.025","DOIUrl":"10.1016/j.actbio.2025.06.025","url":null,"abstract":"<p><p>Intrauterine adhesions (IUAs) present a significant clinical challenge in reproductive medicine with limited effective treatments. Here, we developed an innovative bioactive scaffold using coaxial 3D printing technology to address this unmet need. The scaffold consists of a gelatin methacryloyl (GelMA)-heparin methacryloyl (HepMA) bioink that electrostatically binds and sustains controlled release of heparin-binding epidermal growth factor (HB-EGF). This unique design serves as both a physical barrier to prevent post-injury adhesions and a bioactive delivery system promoting endometrial regeneration through neovascularization. Furthermore, bone marrow-derived mesenchymal stem cells (BMSCs) were incorporated to modulate the local immune microenvironment by polarizing macrophages toward an anti-inflammatory M2 phenotype. Our results demonstrate that this combined approach successfully restored endometrial receptivity, as evidenced by recovered estrogen receptor α (ERα) and progesterone receptor (PR) expression, and ultimately enabled successful pregnancy in an animal model of uterine injury. Comprehensive safety assessments confirm the therapeutic potential of this approach. This multifunctional scaffold represents a promising therapeutic strategy for IUAs, addressing structural, regenerative, and immunological barriers to endometrial repair. STATEMENT OF SIGNIFICANCE: Intrauterine adhesions (IUAs) are a significant complication that can occur following gynecological procedures, affecting approximately 20 % of women after a miscarriage and decreasing the rates of live births. Current treatment options are insufficient, highlighting the urgent need for more effective interventions. To address this issue, we developed a bioactive scaffold using coaxial 3D bioprinting with a biodegradable hydrogel composed of GelMA and HepMA. This scaffold is loaded with stem cells (BMSCs) to help modulate the immune response and includes a sustained-release of growth factors (HB-EGF) to promote re-epithelialization. Our findings indicate that this innovative scaffold not only prevents adhesions but also has the potential to restore fertility, offering a promising strategy to improve outcomes for women at risk of developing IUAs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and mechanical characterisation of an animal model of acute compartment syndrome.","authors":"Carolina Tacchella, Sara Medina-Lombardero, R Eddie Clutton, Graeme McLeod, Yuhang Chen, Michael Crichton","doi":"10.1016/j.actbio.2025.06.026","DOIUrl":"10.1016/j.actbio.2025.06.026","url":null,"abstract":"<p><p>Acute compartment syndrome (ACS) is an orthopaedic emergency that occurs after limb trauma, where increased pressure in muscle compartments disrupts blood flow, risking nerve and muscle damage. Timely diagnosis is essential to avoid permanent harm, but current methods are either invasive, expensive, or subjective. The gold standard remains invasive intracompartmental pressure (IComP) measurement, with other approaches lacking enough evidence to replace it. This study proposes two mechanical tools - mechanical indentation and image-based strain mapping - as simplified methods for ACS assessment. Our work started by establishing a porcine model of ACS, involving intracompartmental gelofusine infusion and pressure measurement in selected muscles of the appendicular skeleton. The IComP could then be adjucted as required from 0 - 40 mmHg (which exceeds the diagnostic threshold of 30 mmHg). With a consistent animal model of ACS, we sought to identify if mechanical methods could measure the internal muscle pressure changes from the surface of the skin. Using a custom-made handheld indenter, we examined the skin overlying muscles during IComP manipulations. Whilst we observed some changes in the mechanical moduli extracted from the indentation force-displacement curves, there was no statistical difference in this method changing pressure. We then used a single-camera digital image correlation (DIC), which showed that as internal pressure increased, corresponding surface skin strains increased. At 30 mmHg the skin reached an average strain of approximately 1.5% although local strains were higher due to an uneven distribution of pressure in the muscle (one reason for the indenter results being so variable). This approach therefore provides a non-invasive diagnostic threshold for ACS in our model and has the potential for clinical use in human patients. STATEMENT OF SIGNIFICANCE: In this study, we established a porcine model of acute compartment syndrome (ACS) to evaluate the mechanical response of skin and muscle under increased intracompartmental pressure (IComP). We developed and tested two non-invasive diagnostic approaches-mechanical indentation and single-camera digital image correlation (DIC)-to assess internal pressure changes from the skin surface. While the indentation method exhibited variability due to uneven pressure distribution, the DIC approach demonstrated a clear relationship between increased IComP and surface strain, identifying a diagnostic threshold of approximately 1.5% strain at 30 mmHg. These findings provide a foundation for the development of non-invasive ACS diagnostic tools that use the mechanical properties of the tissue as a health biomarker (e.g., wearable sensors), offering potential for simplified and cost-effective clinical application.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biodegradable Zn-4Cu-2Se alloy with enhanced work-hardening, antibacterial, and anti-tumor properties for orthopedic applications.","authors":"Miao Zhang, Fei Li, Dechuang Zhang, Yilong Dai, Xiaokai Zhang, Sihan Lin, Yuncang Li, Cuie Wen","doi":"10.1016/j.actbio.2025.06.028","DOIUrl":"10.1016/j.actbio.2025.06.028","url":null,"abstract":"<p><p>Zinc-Selenium (Zn-Se) alloys are promising biodegradable hard-tissue implant materials, particularly due to Se's efficacy in both preventing and treating cancer. However, the difficulty in alloying Zn with Se and the processing softening of Zn alloys seriously hinder the clinical application of Zn-Se alloys. Here, we report on the successful preparation of a Zn-4Cu-2Se alloy using casting and hot rolling, and its extraordinarily effective biocompatibility and antibacterial and anti-tumor capabilities. The microstructural compositions of the Zn-4Cu-2Se alloy prominently featured an η-Zn matrix and the intermetallic phases of ε-CuZn₅ and ZnSe. The hot-rolled Zn-4Cu-2Se alloy demonstrated significant work-hardening behavior under tensile deformation and revealed a yield strength of 215 ± 3 MPa, tensile strength of 234 ± 2 MPa, and fracture strain of 12.1 ± 0.2 %, along with a moderate degradation rate of approximately 56.2 ± 0.3 μm/year in Hanks' solution, meeting the benchmark mechanical and degradation properties for biodegradable orthopedic-implant materials. Furthermore, the hot-rolled Zn-4Cu-2Se alloy demonstrated markedly effective antibacterial capacity against S. aureus and anti-tumor activity against osteosarcoma MG63 cells, and profound biocompatibility and osteogenic capacity toward pre-osteoblast MC3T3-E1 cells. Overall, the hot-rolled Zn-4Cu-2Se alloy holds great promise for orthopedic applications owing to its unique integration of work-hardening behavior and biofunctionalities. STATEMENT OF SIGNIFICANCE: This work reports on the extraordinarily effective biocompatibility and antibacterial and antitumor capabilities of a hot-rolled Zn-4Cu-2Se alloy. The alloy demonstrated significant work-hardening behavior under tensile deformation, with a yield strength of ∼215 MPa, ultimate tensile strength of ∼234 MPa, elongation of ∼12.1 %, and a moderate degradation rate of approximately 56.2 μm/year. Moreover, the alloy showed markedly effective antibacterial ability against S. aureus and antitumor activity against MG63 osteosarcoma cells, and significant biocompatibility and osteogenicity toward pre-osteoblast MC3T3-E1 cells. This Zn-4Cu-2Se alloy is promising for orthopedic applications owing to its unique combination of work-hardening behavior and biofunctional properties.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discoidal nanoparticles exploit thrombus-induced shear gradients to enhance site-specific thrombolysis in stroke.","authors":"Chunping Liu, Jiaoyang Wang, Zhenhua Wang, Xinyu Fan, Jingmei Pan, Xing Guo, Shaobing Zhou","doi":"10.1016/j.actbio.2025.06.027","DOIUrl":"10.1016/j.actbio.2025.06.027","url":null,"abstract":"<p><p>Thromboembolic stroke is characterized by cerebral ischemia caused by arterial thrombosis. Although tissue plasminogen activator (tPA) remains the gold standard for thrombolytic therapy, its clinical use is limited by a narrow therapeutic window and the need for continuous infusion. Nanoparticle-based delivery platforms have been explored to enhance the thrombolytic performance of tPA; however, efficient targeting to thrombus sites remains a key challenge. Notably, thrombosis-induced alterations in blood flow shear stress significantly influence the margination behavior of nanoparticles, which is highly dependent on their morphology and directly impacts thrombus accumulation and lytic efficacy. In this study, we fabricated poly (lactic-co-glycolic acid) (PLGA) nanoparticles with spherical, rod-shaped, and discoidal geometries, and conjugated them with tPA. Among these, discoidal nanoparticles (D-tPA) demonstrated enhanced margination and preferential adhesion to thrombi under high shear conditions, leading to improved thrombolysis and restoration of cerebral perfusion. These findings highlight the critical role of particle shape in vascular drug delivery and position discoidal PLGA nanoparticles as a promising strategy for targeted thrombolytic therapy in ischemic stroke. STATEMENT OF SIGNIFICANCE: This study presents the application of discoidal poly (lactic-co-glycolic acid) (PLGA) nanoparticles for the treatment of thromboembolic stroke, offering an innovative approach to improving drug delivery and thrombolytic efficiency. Compared to spherical or rod-shaped nanoparticles, discoidal nanoparticles exhibit significant margination and thrombus adhesion under high shear stress conditions, thereby enhancing thrombolysis and promoting blood flow restoration. This work opens new avenues for nanomedicine in stroke therapy and holds potential clinical significance for more effective and targeted treatments in vascular diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microindentation reveals softening of the equatorial and anterior sclera during early myopia development in tree shrew eyes.","authors":"Xuesong Zhang, Mustapha El Hamdaoui, Seongjin Lim, Rafael Grytz, Johannes Weickenmeier","doi":"10.1016/j.actbio.2025.05.064","DOIUrl":"10.1016/j.actbio.2025.05.064","url":null,"abstract":"<p><p>Myopia has reached epidemic levels worldwide and significantly increases the risk for blinding diseases such as glaucoma, making it a pressing global health concern. Myopia is commonly associated with biomechanical weakening and remodeling of the sclera, resulting in an excessively elongated eye relative to its optical system. The exact regions of scleral remodeling and tissue softening remain unclear. The purpose of this study was to establish a microindentation testing approach for spatial mapping of scleral stiffness and localization of softened regions. Microindentation tests were performed across entire flat-mounted scleral samples obtained from juvenile tree shrews with either normal visual experience or four days of monocular -5 D lens treatment to induce myopia in one eye, whereas the other eye served as control. Inverse finite element analyses were performed to estimate the apparent modulus at each indentation location, while accounting for large deformations. The generated stiffness maps revealed that scleral stiffness increased with distance from the posterior pole. Compared to normal and control eyes, scleral stiffness was significantly reduced in myopic eyes at the equatorial and anterior scleral regions, but not at the posterior pole. This result was surprising because the posterior pole has previously been regarded as the primary site of scleral remodeling and biomechanical weakening in myopia. Regions that exhibited significant changes in stiffness were also identified as the thinnest scleral regions, suggesting that scleral softening in myopia begins in regions that are most vulnerable to excessive stretching. It remains unclear whether scleral softening at the equatorial and anterior regions during early stages of myopia development is a precursor of biomechanical weakening of the sclera as myopia progresses. This study introduces an indentation-based approach to map scleral stiffness across the entire sclera of tree shrew eyes thus providing higher spatial resolution compared to previous work. This novel approach provides insights into how and where myopic changes may begin, highlighting potential targets for early interventions, such as scleral crosslinking, at structurally vulnerable regions.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitooligosaccharide endowed tunable adhesion to self-gelling powders for rapid hemostasis and sutureless skin wound closure.","authors":"Wan Peng, Yang Zhang, Yefeng Jiang, Youjin Lai, Zilin Kan, Wenxin Geng, Peiming Liu, Pingsheng Liu","doi":"10.1016/j.actbio.2025.06.023","DOIUrl":"10.1016/j.actbio.2025.06.023","url":null,"abstract":"<p><p>Self-gelling powders have recently emerged as promising tissue adhesives for bleeding wound care. However, to simultaneously achieve strong tissue adhesion and on-demand removal without debridement remains a significant challenge. Here, we developed an ultrafast self-gelling powder compositing of acrylic acid/2-aminoethyl methacrylate copolymers (AMA) and chitooligosaccharide (COS). Upon absorbing water/blood from wet tissue surfaces, AMA-COS powders could quickly transform into an integral hydrogel that firmly adhered to tissues (adhesion strength up to 37.74 kPa) based on strong electrostatic interactions, achieving tight wound sealing. Following exposure to COS solutions, the hydrogel exhibited a significant reduction in adhesion strength (3.28 kPa), allowing for easy removal of the adhesive from tissue surfaces. Moreover, the AMA-COS powders could enable effective hemostasis (within 20 s) of acute tail, liver, and stomach bleeding on rats. In vivo studies further validated that the AMA-COS powder-based adhesive could enable rapid & robust adhesion and on-demand removal for sutureless skin incision closure and tissue healing, outperforming surgical sutures and commercial cyanoacrylate glue. These features make AMA-COS powder adhesive to be a promising hemostatic sealant for rapid bleeding control and non-invasive wound closure & tissue repair. STATEMENT OF SIGNIFICANCE: Self-gelling powders have recently emerged as promising tissue adhesives for bleeding wound care. However, achieving reliable tissue adhesion while enabling on-demand removal without debridement remains a significant challenge. This work developed a new type of ultrafast self-gelling powder (AMA-COS) with tunable tissue adhesion on varying complexation with chitooligosaccharide (COS) for rapid hemostasis and sutureless skin wound closure. The AMA-COS powders can quickly gel and firmly adhere to tissue surfaces upon water/blood absorption, forming tight wound sealing, while it is able to easily detach from tissue merely by exposure to additional COS solutions. We believe the AMA-COS powder could be a high-efficiency multi-functional fault-tolerant bioadhesive for rapid bleeding control and non-invasive wound closure and tissue repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clickable PEG-norbornene microgels support suspension bioprinting and microvascular assembly.","authors":"Irene W Zhang, Lucia S Choi, Nicole E Friend, Atticus J McCoy, Firaol S Midekssa, Michael M Hu, Eben Alsberg, Sasha Cai Lesher-Pérez, Jan P Stegemann, Brendon M Baker, Andrew J Putnam","doi":"10.1016/j.actbio.2025.06.006","DOIUrl":"10.1016/j.actbio.2025.06.006","url":null,"abstract":"<p><p>The development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. The clickable PEGNB microbead slurry exhibited mechanical behavior suitable for suspension bioprinting of sacrificial bioinks, could be UV crosslinked into a granular construct post-print, and withstood evacuation of the bioink and subsequent perfusion of the patterned void space. Endothelial and stromal cells co-embedded within jammed RGD-modified PEGNB microbead slurries assembled into capillary-scale vasculature after secondary crosslinking of the beads into granular constructs, with endothelial tubules forming within the interstitial space between microbeads and supported by the perivascular association of the stromal cells. Microvascular self-assembly was not impacted by printing sacrificial bioinks into the cell-laden microbead support bath before UV crosslinking. Collectively, these results demonstrate that clickable PEGNB microbeads are a versatile substrate for both suspension printing and microvascular culture and may be the foundation for a promising methodology to engineer hierarchical vasculature. STATEMENT OF SIGNIFICANCE: In this study, we leveraged and combined advances in microgel biomaterials, granular hydrogels, suspension bioprinting, and vascular biology to create relatively large volume (>500 mm³) vascularized constructs. We fabricated secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads and demonstrated their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. To the best of our knowledge, this is the first study that uses PEG microgels as supportive materials for bioprinting, and one of the first papers to document microvascular self-assembly within granular constructs. The combination of top-down and bottom-up approaches within a single construct represents a significant and innovative contribution that we believe will be of broad interest to the biomaterials and regenerative medicine communities.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Janus hydrogels delivering low-density lipoprotein receptor-related protein 6 inhibitor enhance myocardial repair via m6A-dependent cuproptosis in bama pigs.","authors":"Feila Liu, Tingting Liang, Jun Liu, Peng Qu, Shiqi Han, Dayu Sun, Yansha Hao, Yue Zhou, Xue Li, Cui Ma, Hongyan Zhang, Yunbo Luo, Yali Wang, Ju Tan, Qian Lei, Chuhong Zhu, Panke Cheng","doi":"10.1016/j.actbio.2025.06.018","DOIUrl":"10.1016/j.actbio.2025.06.018","url":null,"abstract":"<p><p>Copper overload induces a unique form of cell death called cuproptosis via mitochondrial ROS accumulation. Following myocardial infarction (MI), copper ion levels rise significantly in infarcted tissue. Cardiomyocytes, highly sensitive to copper, respond through activation and nuclear translocation of LRP6, which interacts with ALKBH5 to suppress m6A modification of ferredoxin 1 (FDX1), thereby exacerbating copper toxicity. LRP6 also facilitates copper influx, further promoting cuproptosis. High-throughput screening identified chrysin-7-O-glucuronide (C7Og) as a potent LRP6 inhibitor that mitigates cuproptosis without compromising cardiac protective effects. Moreover, a Janus hydrogel enhanced with benzalkonium chloride-modified tannic acid improves tissue adhesion and glucose delivery. A myocardial patch integrating C7Og within this hydrogel significantly reduced infarct size and improved cardiac function in both rat and Bama miniature pig models, highlighting strong translational potential for MI therapy. STATEMENT OF SIGNIFICANCE: This study uncovers a mechanism of copper-induced cell death, termed cuproptosis, in myocardial infarction (MI). It identifies low-density lipoprotein receptor-related protein 6 (LRP6) as a key regulator of copper influx and cuproptosis, revealing a potential target for mitigating copper toxicity in cardiac tissue. Chrysin-7-O-glucuronide (C7Og), a potent LRP6 inhibitor, offers a promising strategy to prevent LRP6-mediated cell death while preserving its protective role in cardiac function. Encapsulating C7Og in a Janus hydrogel enhances its delivery and adhesion, demonstrating significant efficacy in reducing myocardial damage and improving cardiac function in rat and Bama miniature pig models. This work offers new insights into copper homeostasis and presents a potential therapeutic approach for MI treatment.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sonosensitizer-doped framework theranostic nanoprobe for enhanced spatiotemporal eradication of helicobacter pylori with photoacoustic imaging guidance.","authors":"Zixuan Zhang, Jiahai Lin, Xinyan Dai, Xinyue Li, Faqi Huang, Shan Qin, Erqun Song, Weihong Tan","doi":"10.1016/j.actbio.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.008","url":null,"abstract":"<p><p>Helicobacter pylori (H. pylori) infection is the leading cause of gastric cancer. Current antibiotic-based H. pylori suppression therapy suffers from low efficacy, drug resistance, and intestinal flora imbalance, which makes an accurate, controllable, and safe H. pylori inhibition strategy urgent. Here, we present a theranostic nanoprobe, UPE@ZH, which integrates sonodynamic therapy and urease inactivation guided by photoacoustic imaging. The UPE@ZH nanoprobe consists of a sonosensitizer and photoacoustic agent, hematoporphyrin monomethyl ether (HMME), doped into a zeolitic imidazolate framework (ZIF-8) and coated with the pH-responsive polymer Ureido-PEG2000-modified polyacrylic resin (UPE). When administered orally to H. pylori-infected mice, the UPE@ZH nanoprobe collapses gradually in the acidic environment of H. pylori infection, while HMME and zinc ion release occur, resulting in the synergistic eradication of H. pylori through HMME-based sonodynamic therapy and zinc ion-based urease inactivation, under the guidance of photoacoustic imaging. This approach offers a promising, efficient, and safe treatment strategy for H. pylori infection with minimized risk of side effects. STATEMENT OF SIGNIFICANCE: Helicobacter pylori (H. pylori) infection has emerged as a growing public health threat. The current triple antibiotic therapy suffers from limited therapeutic efficacy and carries inherent risks of drug resistance and intestinal microbiota dysbiosis. To address these challenges, we developed a novel strategy for photoacoustic imaging-guided antibiotic-free therapeutic based on a theranostic nanoprobe composed of sonosensitizer-doped zeolitic-imidazolate framework, achieving spatiotemporal and enhanced eradication for H. pylori safely. This study makes not only an important contribution to the treatment of H. pylori-related infections but also has general interest to researchers in a broad range of fields, including bacterial eradication, drug delivery, and in vivo imaging.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent effects of premineralization and prevascularization on osteogenesis and vascular integration in humanized tissue engineered bone constructs.","authors":"Sugandha Bhatia, Luke Hipwood, Briony Claxton, Agathe Bessot, Angus Weekes, Kamil Sokolowski, Tomoji Mashimo, Nathalie Bock, Jacqui McGovern","doi":"10.1016/j.actbio.2025.06.019","DOIUrl":"10.1016/j.actbio.2025.06.019","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Osteogenesis (bone formation) and vascularization (blood vessel formation) are two central and interconnected physiological-relevant processes in bone formation. Prevascularization of humanized tissue-engineered bone constructs (hTEBCs) has been proposed to better mimic the human bone microenvironment by enhancing vascular integration and facilitating greater osteogenic capacity. Here, we investigated the effects of premineralization and prevascularization on bone and vasculature development in an ectopic hTEBC model using a scaffold-hydrogel composite approach. Human osteoblast cells (hOBs) were cultured under osteogenic conditions (OM), with or without a 3-day mineralization boost (OM+) period for 4 weeks prior to implantation in vivo in a supporting porous polycaprolactone (mPCL) scaffold. Separately, photocrosslinkable fish gelatin-derived hydrogels placed within supporting mPCL scaffolds showed formation of elongated vascular networks as early as day 3 with in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem/stromal cells (MSCs). The OM and OM+ cultured constructs were subcutaneously implanted into immunocompromised rats with and without the prevascular hydrogels, resulting in four subgroups: OM, OM+, OM/Vas, and OM+/Vas. Our results demonstrated that the OM+ group led to more rapid osteoinduction and enhanced osteogenic differentiation in vivo with woven bone structure and active remodeling. Conversely, prevascularization (OM/Vas, OM+/Vas groups) led to reduce in vivo bone volume and density but promoted the development of human endothelial networks and successful anastomosis with host vasculature. Our study highlights the distinct contributions of premineralization and prevascularization, where premineralization is critical for robust bone formation and prevascularization enhances vascular integration, providing important insights for advancing the physiological relevance of hTEBC models in animal hosts. STATEMENT OF SIGNIFICANCE: This study demonstrates the development of humanized tissue engineered bone constructs incorporating a vascular niche using a rat. By integrating innovative premineralization and prevascularization techniques within scaffold-hydrogel composites, we show that premineralization accelerates bone formation, while prevascularization promotes endothelial network formation and integration with host vasculature. Photocrosslinkable, low-stiffness LunaGel™ hydrogels enhanced microcapillary-like structure formation and endothelial sprouting in in vitro co-culture. However, by combining osteogenic and vascular cues within a biodegradable composite, this work advances the bone tissue engineering field by creating a model that more accurately reflects the divergent and competing nature of vascularization and bone formation. This platform has broad applicability for studying bone-vascular interactions and may inform strategies to improve the design of biomaterials f","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}