Acta biomaterialia最新文献

{"title":"Revolution in Organ Preservation: Technological Exploration.","authors":"Xin-Yuan Kang, Jia-Yi Cheng, Wan-Yi Ge, Yi-Ming Tong, Da-Chuan Yin","doi":"10.1016/j.actbio.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.008","url":null,"abstract":"<p><p>Organ preservation plays a critical role in addressing transplantation challenges, including donor shortages and ischemia-reperfusion injury (IRI). Continuous advancements in preservation technologies are essential to meet the increasing demand for transplantable organs. This review provides a comprehensive analysis of organ preservation techniques, spanning from hypothermic storage to advanced methods such as supercooling, vitrification, and partial freezing. Historical milestones, including the development of the EuroCollins, University of Wisconsin (UW), ET-Kyoto, and Celsior solutions, are discussed alongside innovations in machine perfusion and cryopreservation technologies. Particular emphasis is placed on the underlying mechanisms of these techniques, such as metabolic rate suppression, prevention of ice crystal formation, and the application of cryoprotectants, all aimed at extending preservation duration and improving organ quality. Emerging trends, such as the integration of nanotechnology and artificial organ cultivation, are highlighted as promising directions to enhance preservation efficiency. By exploring current advancements and future trends, this review underscores the importance of technological innovation in addressing the global organ shortage crisis and improving transplantation outcomes. STATEMENT OF SIGNIFICANCE: This review offers a comprehensive analysis of the advancements in organ preservation technologies, a critical area in addressing the global organ shortage crisis. By detailing the evolution from early perfusion techniques to cutting-edge innovations like supercooling, vitrification, and nanotechnology, the work underscores the importance of extending organ viability and improving transplant outcomes. Importantly, it bridges historical milestones with emerging trends, showcasing how integration of novel materials and methodologies can revolutionize organ transplantation. This work not only enriches the scientific understanding of organ preservation but also opens pathways for interdisciplinary innovations, setting the stage for the development of sustainable and efficient organ banks. By aligning technological advancements with clinical challenges, it provides actionable insights that could reshape transplantation medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030959","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":"Extracellular matrix repair and organization of chronic infected diabetic wounds treated with MACF hydrogels.","authors":"Hannah A Durr, Shahrzad Abri, Samuel D Salinas, Kayla Adkins-Travis, Rouzbeh Amini, Leah P Shriver, Nic D Leipzig","doi":"10.1016/j.actbio.2025.04.062","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.062","url":null,"abstract":"<p><p>Diabetic foot ulcers (DFUs) are a multifactorial medical problem that require multifaceted approaches for effective healing. Most research on DFU healing has concentrated on promoting wound closure, with less emphasis on the quality of repaired tissue. This is problematic, however, since quality of the repaired tissues can have potential to improve wound healing outcomes and limit re-ulceration. If more functionally active dermis replaces the lost tissue, this can effectively maximize strength, organization, and overall structure of the plantar surface. Additionally, DFUs commonly show multi-strain infection, which further exacerbates the non-healing status of these wounds. Treatment of chronic wounds can be benefitted by application of oxygen and localized infection treatment, both can be achieved via our methacrylated chitosan-based (MACF) hydrogel. A non-healing diabetic infected wound model was used to explore extracellular matrix (ECM) organization, tensile strength, and metabolomic profiles at a 21-day endpoint as a marker for maturation and improved functionality of repaired tissues over normal scar formation. Effective remediation of infection was achieved with 14 days of polyhexamethylene biguanide (PHMB) application with improved wound repair compared to continuous treatment. Prolonged (21 day) application of PHMB showed resulting necrosis, although standard application times for patients with infected wounds can reach up to 28 continuous days. Biaxial mechanical analysis showed improved isotropic strength of infected tissues treated with MACF with PHMB stopped on D14, supported by collagen fiber orientation in second harmonics generation (SHG) imaging. Oxygenating MACF treatments also improved collagen deposition through the enhancement of the hydroxyproline fibrillary collagen synthesis pathway. These structural and mechanical results demonstrate a promising potential treatment for infected diabetic foot ulcers which shows improved dermal functionality. STATEMENT OF SIGNIFICANCE: Diabetic foot ulcers are a multifaceted problem in the medical field exacerbated by infection, with potential for gangrene, lower limb amputation, sepsis, or death. Current treatment regimens include oxygen therapy, physical debridement, and strong antibacterials. However, there is a lack of multi-faceted approaches, which we have designed in our oxygenating chitosan-based hydrogels capable of delivering antibiotics. Treatments currently focus on closure of wounds; however, functionality of regenerated tissues are limited due to fibrotic scar formation. Therefore, we have chosen to focus not only on closure, but also quality of regenerated tissues through mechanical testing and analysis of extracellular matrix composition and organization, with a goal of improving functionality of regenerated tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000366","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":"Trimethylamine N-Oxide-Derived Zwitterion Coating for Polyurethane Ureteral Stents Prevents Encrustation Formation.","authors":"Kaiguo Xia, Guang Chen, Bingbing Hou, Zhe Wang, Yaqi Zhu, Yuexian Xu, Shanfu Zhang, Qiang Xuan, Yezi You, Zongyao Hao","doi":"10.1016/j.actbio.2025.04.058","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.058","url":null,"abstract":"<p><p>A ureteral stent with strong resistance to proteins, bacteria, and multivalent ions is crucial for the safe treatment of urologic diseases. Generally, the proteins, bacteria, and multivalent ions present in urine tend to bind to the stent surface, leading to aggregation, nucleation, and subsequent stent encrustation. Stent encrustation can induce or exacerbate urinary tract infections and obstructions, thereby seriously harming kidney function. Although hydrophilic coatings on ureteral stents can reduce the binding of proteins, bacteria, and multivalent ions, encrustation still occurs. To date, preventing stent encrustation formation remains a significant challenge. Here, we grafted dense trimethylamine oxide (TMAO)-derived zwitterionic polymers onto the stent surface via a branched amplification strategy. These zwitterions can strongly bind water molecules, forming a stable hydration shell that repels proteins, bacteria, and multivalent ions from adhering to the surface of the polyurethane ureteral stent, thus rendering the stent anti-encrustation. The results showed that the TMAO-derived zwitterion-coated stents exhibited a significantly reduced encrustation weight (13.8% of the original polyurethane stent) and demonstrated good safety. This approach offers a promising method for enhancing stent encrustation resistance. STATEMENT OF SIGNIFICANCE: This study successfully developed a TMAO-derived zwitterionic coating on the surface of a polyurethane stent, creating a superhydrophilic surface with a minimal contact angle of 5.2^o. This surface effectively shields the stent from interactions with proteins, bacteria, and multivalent ions in urine, demonstrating favorable anti-protein adsorption and antibacterial adhesion properties. The superhydrophilic surface formed by the TMAO-derived zwitterionic coating on the stents (PTMAO-s) provides strong anti-fouling resistance and enhanced anti-encrustation properties. Under identical conditions, the encrustation resistance of PTMAO-s is approximately 7.2-fold greater than that of original polyurethane stents (PU), 3.6-fold greater than Bard commercial stents, and 2.1-fold greater than betaine-coated stents (PSBG-s).</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994093","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":"Invasive phenotypes of triple-negative breast cancer-associated fibroblasts are mechanosensitive, AhR-dependent and correlate with disease state.","authors":"Gabrielle Brewer, Paul Savage, Anne-Marie Fortier, Hong Zhao, Alain Pacis, Yu-Chang Wang, Dongmei Zuo, Monyse de Nobrega, Annika Pedersen, Camille Cassel de Camps, Margarita Souleimanova, Valentina Muñoz Ramos, Jiannis Ragoussis, Morag Park, Christopher Moraes","doi":"10.1016/j.actbio.2025.04.061","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.061","url":null,"abstract":"<p><p>Cancer associated fibroblasts (CAFs) play a critically important role in facilitating tumour cell invasion during metastasis. They also modulate local biophysical features of the tumour microenvironment through the formation of fibrotic foci, which have been correlated with breast cancer aggression. However, the impact of the evolving three-dimensional biophysical tumour microenvironment on CAF function remains undefined. Here, by isolating CAFs from primary human triple-negative breast cancer tissue at the time of surgery, we find that their ability to remodel the local microenvironment and invade into a three-dimensional matrix correlates with disease state. We then engineered culture models to systematically deconstruct and recreate mechanical tissue features of early breast cancer fibrotic foci; and demonstrate that invasion is mechanically-activated only in CAFs from patients with no detectable pre-existing metastases, but is independent of mechanical cues in CAFs isolated from patients with later-stage axillary lymph node metastases. By comparing the differential transcriptional response of these cells to microenvironmental tissue stiffness, we identify the aryl hydrocarbon receptor (AhR) as being significantly upregulated in invasive sub-populations of both mechanically-activated and mechanically-insensitive CAFs. Increasing AhR expression in CAFs induced invasion, while suppressing AhR significantly reduced invasion in both mechanically-activated and mechanically-insensitive CAF populations, even on stiffnesses that recapitulate late-stage disease. This work therefore uses mechanobiological analyses to identify AhR as a mediator of CAF invasion, providing a potential stratification marker to identify those patients who might respond to future mechanics-based prophylactic therapies, and provides a targetable mechanism to limit CAF-associated metastatic disease progression in triple-negative breast cancer patients. STATEMENT OF SIGNIFICANCE: By designing a mechanically-tunable tissue-engineered model of fibroblastic foci, and using this to culture patient-derived cancer-associated fibroblasts, we demonstrate that these cells are differentially mechanosensitive, depending on disease stage of the patient. While comparing transcriptomic profiles of patient-derived cells produces too many pathways to screen, identifying the pathways activated by local tissue mechanics that were common across each patient allowed us to identify a specific target to limit fibroblast invasion. This broad discovery strategy may be useful across a variety of biomaterials-based tissue engineered models; and these specific findings suggest (1) a strategy to identify patients who might respond to CAF- or matrix-targeting therapies, and (2) a specific actionable target to limit CAF-associated metastatic disease progression.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044689","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":"Insights into the osteosarcoma microenvironment: Multiscale analysis of structural and mineral heterogeneity.","authors":"Francesca Rossi, Martyna Malgorzata Rydzyk, Luisa Barba, Emil Malucelli, Maria Elisabetta Federica Palamà, Chiara Gentili, Maddalena Mastrogiacomo, Alessia Cedola, Lucia Mancini, Murielle Salomé, Hiram Castillo-Michel, Davide Maria Donati, Marco Gambarotti, Enrico Lucarelli, Michela Fratini, Stefano Iotti","doi":"10.1016/j.actbio.2025.04.057","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.057","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a malignant and heterogeneous disease that typically originates in the long bones of children and adolescents. It is characterized by the presence of immature cells having an aggressive phenotype and rapid uncontrolled proliferation. OS progression induces significant molecular and cellular changes locally within the bone, resulting in the development of an abnormal tumor microenvironment (TME). The OS TME plays a crucial role in tumor progression and development, however, the precise effects of OS on bone structure and mineralization still remain poorly understood. In this study, we examined the OS TME by analyzing samples from osteoblastic, parosteal, and periosteal osteosarcomas. Employing advanced synchrotron-based X-ray techniques, we performed a multiscale analysis to evaluate the structural and mineral complexity of tumor-affected bone. Our results revealed marked morphological differences among the osteosarcoma subtypes, while confirming that biomineralization remains active through the production of hydroxyapatite (HA). X-ray diffraction identified two distinct hydroxyapatite crystalline phases across all samples, suggesting a critical behavior of minerals in bone. Additionally, we observed that the bone mineral structure in periosteal and parosteal osteosarcomas exhibited crystal deformations along the c-axis, whereas the osteoblastic osteosarcoma displayed a mineral profile comparable to control bone. Micro-X-ray absorption near-edge spectroscopy revealed the occurrence of a dysregulated biomineralization in the parosteal and periosteal subtypes, marked by the presence of calcium compounds different from HA, in contrast to the mature mineral state found in the osteoblastic variant. These findings highlight the complexity of osteosarcoma repercussion on bone tissue, offering new insights into the interactions within the OS TME. STATEMENT OF SIGNIFICANCE: This study investigates the tumor microenvironment (TME) of osteosarcoma (OS), a rare and aggressive bone cancer mainly affecting children and adolescents. Using advanced synchrotron-based X-ray techniques, we analyzed structural and mineral alterations in bone from three OS subtypes: osteoblastic, parosteal, and periosteal. The results reveal distinct subtype-specific differences in bone mineralization and crystallinity, highlighting the heterogeneity of OS and the pivotal role of its microenvironment in driving disease progression. This research contributes to our understanding of OS pathophysiology and provides foundation for future studies aimed at developing targeted therapies and improving diagnostic approaches.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045850","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":"RGD peptide hydrogel downregulates mechanosignal YAP to inhibit postoperative scarring.","authors":"Yao Lv, Licheng Liang, Mian Qin, Ru-Ping Jiang, Fei-Fei Zong, Xia Wu, Kai-Li Wu, Liang Liang","doi":"10.1016/j.actbio.2025.04.059","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.059","url":null,"abstract":"<p><strong>Objective: </strong>Glaucoma filtration failure may result from an overabundance of human Tenon's capsule fibroblasts (HTFs) forming a filtration tract scar. Conversely, the Yes-associated protein (YAP), a transcriptional activator of the Hippo signaling pathway, is a crucial matrix stiffness regulator of matrix production and fibroblast activation. With superior biocompatibility and biodegradability, RGD peptide hydrogels imitate the structure of real tissues' extracellular matrix (ECM). The purpose of this research was to determine whether down-regulating YAP expression via RGD peptide hydrogels may prevent HTFs activation and ECM protein secretion. Transforming growth factor-β2 (TGF-β2) was used to induce the activation of HTFs in a cellular model of scarring following glaucoma filtration surgery. Utilizing SD rats, a murine model of subconjunctival injury was established. The shape of collagen fibers was observed through Masson staining, and the expression of YAP and α-smooth muscle actin (α-SMA) was identified through immunohistochemistry. RGD peptide hydrogel was discovered to have anti-scarring properties in a mouse eye injury model, as well as the ability to lessen HTFs activation, YAP expression, cytosolic nucleus accumulation, and the expression of connective tissue growth factor (CTGF) and ECM proteins. The best concentration was found to be 1.0 weight percent among them. This concentration not only makes it easier to inject a drug subconjunctivally in vivo and maintain the filtration vesicle space in the conjunctiva, but it also inhibits the activation of fibroblasts into myofibroblasts and down-regulates the expression of the Hippo-YAP signaling pathway in Tenon's capsule fibroblasts.</p><p><strong>Statement of significance: </strong>1. The homogenous reticular three-dimensional nanostructure that made up the interior structure of the 1.0 weight percent gel had good drug delivery characteristics for long-lasting controlled drug release. 2. RGD peptide hydrogel had a certain matrix hardness, which could mimic the normal connective tissue hardness under the conjunctiva. 3. RGD peptide hydrogels could prevented the development of rat conjunctival fibrosis. 4. RGD peptide hydrogel could inhibit the expression of YAP and its target gene CTGF, as well as α-SMA, ECM proteins in HTFs. 5. RGD peptide hydrogel has good biocompatibility, biodegradability, and stable mechanical properties, and can also be used as a promising carrier for the controlled release of drugs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044691","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":"Biodegradable Zn-Li-Mn alloy to achieve optimal strength and ductility for bone implants.","authors":"Danni Shen, Yahong Li, Jiahui Shi, Ting Zhang, Jing-Jun Nie, Dafu Chen, Dandan Xia, Yufeng Zheng","doi":"10.1016/j.actbio.2025.04.056","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.056","url":null,"abstract":"<p><p>Biodegradable zinc-based metals have received attention due to their strength, biodegradability, and desirable biocompatibility. However, the trade-off between strength and ductility has limited their use. Here, we designed a biodegradable Zn-Li-Mn ternary alloy with superior strength and ductility. The ultimate tensile strength (UTS) of Zn-0.4Li-xMn (x = 0.1, 0.4, and 0.8) alloys reached 438.74-469.96 MPa, similar to pure Ti, with elongation reaching 41.52%-54.91%, surpassing other Zn-Li-based alloys. We investigated the biodegradation behavior and osteogenic effects of the Zn-Li-Mn alloys both in vitro and in vivo. Immersion tests demonstrated that the alloys exhibited a more uniform degradation morphology with significantly less release of Zn²⁺ ion compared to pure Zn. Cytocompatibility, hemocompatibility, and histological analyses demonstrated their biosafety. In addition, Zn-Li-Mn alloy extracts significantly enhanced osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs), manifesting higher alkaline phosphatase activity, increased biomineralization, and elevated osteogenic gene expression. Zn-0.4Li-0.8Mn alloy showed the highest osteogenic activity in vitro. When implanted in rat femoral condyles, it demonstrated improved in vivo bone regeneration effects, exhibiting enhanced osteointegration. Transcriptomic analysis revealed that Zn²⁺, Mn²⁺, and Li⁺ ions released from Zn-Li-Mn alloy collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, prompting osteogenic differentiation. These findings demonstrate the high potential of the Zn-0.4Li-0.8Mn alloy for bone implants. STATEMENT OF SIGNIFICANCE: 1. Biodegradable Zn-Li-Mn ternary alloy with superior mechanical strength and excellent ductility were designed. 2. Enhanced osteointegration were observed in Zn-0.4Li-0.8Mn implants in vivo. 3. Transcriptomic analysis revealed that the Zn²⁺, Mn²⁺, and Li⁺ released from Zn-0.4Li-0.8Mn collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, enhancing osteogenesis.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060770","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":"Construction of Z-Scheme MOF-on-MOF Heterostructures for Mitochondria-Targeted Sonodynamic Therapy.","authors":"Yilin Yang, Zhihua Wang, Ning Wang, Fei Yan, Zhan Shi, Shouhua Feng","doi":"10.1016/j.actbio.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.001","url":null,"abstract":"<p><p>Metal-organic framework (MOF)-based nano-sonosensitizers are promising for antitumor sonodynamic therapy (SDT). Under ultrasound (US) irradiation, MOF-based sonosensitizers can generate reactive oxygen species (ROS), thereby exerting cytotoxic effects on tumor cells. However, their low electron-hole (e^-/h⁺) separation efficiency and limited tumor-targeting capability hinder the therapeutic efficacy of SDT. In this study, these challenges were addressed by developing a MOF-on-MOF Z-scheme heterojunction GaMOF/TiMOF (GM/TM) to enable mitochondria-targeted SDT. Research on gallium (Ga)-based materials in the field of antitumor treatment is continuously advancing, particularly in targeted therapy and combination therapy. The GM/TM heterojunction was constructed by epitaxially growing GaMOF on the surface of NH₂-MIL-125 (TiMOF), forming a structure that effectively enhances charge transfer and prevents rapid e^-/h⁺ recombination, significantly enhancing ROS generation and apoptosis under US irradiation. Additionally, the presence of surface Ga³⁺ enables efficient mitochondrial targeting in tumor cells, leading to altered membrane permeability, mitochondrial iron overload, and the initiation of ferroptosis via lipid peroxidation. These synergistic effects collectively result in potent antitumor efficacy. This study conceptually introduces the MOF-on-MOF heterojunction as a multifunctional sonosensitizer for mitochondria-targeted tumor therapy, offering a reference for the development of SDT and providing insights into the bioavailability and potential applications of gallium-based materials in antitumor treatment. STATEMENT OF SIGNIFICANCE: In this study, we developed a MOF-on-MOF composite ultrasound-sensitive platform targeting mitochondria to improve the efficacy of SDT in complex tumor lesions. It integrated apoptosis and ferroptosis to enhance anti-tumor SDT via ultrasound. The Z-scheme heterostructure sonosensitizer GaMOF/TiMOF significantly enhanced ROS generation under ultrasound and accumulated in mitochondria, making them the primary target for SDT. Moreover, the damage to mitochondrial function caused by GaMOF/TiMOF led to an imbalance of endogenous iron and oxidative stress, inducing mitochondrial-associated ferroptosis. This, in turn, triggered lipid peroxidation in conjunction with high levels of ROS generated by ultrasound, significantly enhancing the anti-tumor effects of SDT. This work provided a new strategy for efficient and safe sonosensitizer modification and proposed an innovative mitochondrial-targeted therapeutic approach.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056025","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":"Do human brain white matter and brain stem structures show direction-dependent mechanical behavior?","authors":"Nina Reiter, Sophia Auer, Lucas Hoffmann, Lars Bräuer, Friedrich Paulsen, Silvia Budday","doi":"10.1016/j.actbio.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.004","url":null,"abstract":"<p><p>Since the corpus callosum and the brain stem are both vulnerable to diffuse axonal injury during head impacts, there is a high interest in modeling the mechanical behavior of these brain structures. In recent years, different versions of fiber-reinforced material models have been proposed for the corpus callosum and other white matter regions, as well as for the brain stem, even though there is currently no consensus on whether those structures exhibit a significant direction-dependent behavior during mechanical loading. Here, we present the first large-strain, multimodal experimental study on human brain tissue that includes the corpus callosum and the lower brain stem (medulla oblongata) tested along two different directions. Additionally, we compare those two structures with other white matter (corona radiata, cerebellar white matter) and brain stem structures (pons, midbrain) to highlight differences in their material response. Cyclic compression-tension and shear tests reveal statistically significant direction-dependent material behavior in the corpus callosum. Directional differences in the brain stem are not statistically significant and do not indicate a clear directionality. Combined with histological findings, our results suggest that the mechanical behavior of white matter structures is influenced not only by axon caliber, orientation and density, but also by the architectural organization, i.e., clustering versus even distribution, of cells and tracts, and possibly vascular density. These findings highlight the need for micromechanical constitutive models for brain white matter that do not merely include axons embedded in a matrix. Statement of significance Mechanical head injuries often result in insults like diffuse axonal injury in white matter regions of the human brain. Therefore, there is a high interest in understanding and predicting the mechanical properties of those regions in order to prevent injury and advance diagnosis and treatment strategies of neurological disorders. There has been a long controversy regarding the question whether human brain white matter regions show an anisotropic, direction-dependent mechanical response. With the goal of providing experimental evidence to conclusively answer this question, we here present large-strain, multimodal experimental data and representative histological analyses of different human brain white matter regions and brain stem structures, including directional investigations for both the corpus callosum and the medulla oblongata (lower brain stem).</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032006","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":"Catechol crosslinked bioprosthetic valves derived from caffeic acid and dopamine-conjugated porcine pericardia exhibit enhanced antithrombotic, immunomodulatory and anticalcification performance.","authors":"Lepeng Chen, Bangquan Wei, Xueyu Huang, Li Yang, Rifang Luo, Cheng Zheng, Yunbing Wang","doi":"10.1016/j.actbio.2025.04.054","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.054","url":null,"abstract":"<p><p>The global aging population has led to an increasing prevalence of valvular heart disease (VHD), and the clinical application of bioprosthetic heart valves (BHVs) are growing with the advancement of transcatheter heart valve replacement surgery. However, BHVs, as xenogeneic pericardial tissue crosslinked with glutaraldehyde, have been affected by suboptimal cytocompatibility, thrombosis, immune response, and calcification, leading to premature degeneration and failure. Herein, a catechol-crosslinking strategy for BHVs was developed by conjugating porcine pericardia (PP) with catechols and subsequently coupling the grafted catechols to achieve the crosslinking and stabilization of BHVs. Caffeic acid and dopamine were exploited to conjugate the bioactive catechols on PP through amide condensation, and the catechols were further coupled under oxidation to impart the PP with enhanced stability and cytocompatibility as well as comparable mechanical properties to those of glutaraldehyde crosslinked PP (GLUT-PP). With the enrichment of catechols, the crosslinked PP not only demonstrated improved hydrophilicity to resist the blood components adhesion and thrombosis, but also enhanced the performance of endothelialization and antioxidation. Furthermore, the introduced catechols exhibits favorable anti-inflammatory properties, which significantly ameliorated the foreign body response and regulated the local immune responses of crosslinked PP. In conclusion, the catechol crosslinked PP is expected to be explored as a potential substitute for GLUT-PP to extend the lifespan of BHVs. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valves (BHVs) are mainly prepared from glutaraldehyde crosslinked porcine or bovine pericardia (GLUT-PP). Currently, BHVs are affected by cytotoxicity, thrombosis, calcification, and immunoinflammatory responses, which would accelerate degeneration and failure of BHVs. In this study, we developed a catechol crosslinking strategy for BHVs and engineered caffeic acid and dopamine-conjugated porcine pericardia (PP). In summary, catechol crosslinked porcine pericardia demonstrated enhanced collagen stability, antithrombosis, endothelialization, anticalcification and immunomodulation which reduced the risk of structural degeneration, suggesting that the catechol crosslinked porcine pericardia could serve as a potential alternative to GLUT-PP.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037173","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}