Bioactive MaterialsPub Date : 2024-10-24DOI: 10.1016/j.bioactmat.2024.10.020
{"title":"Periosteum-bone inspired hierarchical scaffold with endogenous piezoelectricity for neuro-vascularized bone regeneration","authors":"","doi":"10.1016/j.bioactmat.2024.10.020","DOIUrl":"10.1016/j.bioactmat.2024.10.020","url":null,"abstract":"<div><div>The development of scaffolds for repairing critical-sized bone defects heavily relies on establishing a neuro-vascularized network for proper penetration of nerves and blood vessels. Despite significant advancements in using artificial bone-like scaffolds infused with various agents, challenges remain. Natural bone tissue consists of a porous bone matrix surrounded by a neuro-vascularized periosteum, with unique piezoelectric properties essential for bone growth. Drawing inspiration from this assembly, we developed a periosteum-bone-mimicking bilayer scaffold with piezoelectric properties for regeneration of critical-sized bone defects. The periosteum-like layer of this scaffold features a double network hydrogel composed of chelated alginate, gelatin methacrylate, and sintered whitlockite nanoparticles, emulating the viscoelastic and piezoelectric properties of the natural periosteum. The bone-like layer is composed of a porous structure of chitosan and bioactive hydroxyapatite created through a biomineralization process. Unlike conventional bone-like scaffolds, this bioinspired bilayer scaffold significantly enhances osteogenesis, angiogenesis, and neurogenesis combined with low-intensity pulsed ultrasound-assisted piezoelectric stimulation. Such a scheme enhances neuro-vascularized bone regeneration <em>in vivo</em>. The results suggest that the bilayer scaffold could serve as an effective self-powered electrical stimulator to expedite bone regeneration under dynamic physical stimulation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532335","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}
Bioactive MaterialsPub Date : 2024-10-23DOI: 10.1016/j.bioactmat.2024.10.014
{"title":"An injectable hyaluronic acid/lithium calcium silicate soft tissue filler with vascularization and collagen regeneration","authors":"","doi":"10.1016/j.bioactmat.2024.10.014","DOIUrl":"10.1016/j.bioactmat.2024.10.014","url":null,"abstract":"<div><div>The significance of collagen and vascular in skin augmentation have been recognized in recent years. However, current skin tissue fillers, <em>e.g.</em> hyaluronic acid (HA) or HA-based hydrogel, fail to meet the perfect augmentation requirements due to their inadequate long-term support effect and the lack of tissue-inducing activity. Herein, an injectable skin filler containing hyaluronic acid (HA) hydrogel and lithium calcium silicate (LCS, Li<sub>2</sub>Ca<sub>4</sub>Si<sub>4</sub>O<sub>13</sub>) bioceramic microspheres was developed for skin tissue fillers, owing to the excellent biological function of silicate bioceramics. The HA-LCS fillers could be easily injected through a tiny standard medical needle (27 G) with force of less than 36 N, and showed good biocompatibility both <em>in vitro</em> and <em>in vivo</em>. Furthermore, the bioactive ions released from HA-LCS fillers significantly enhanced the expression of vascularization-related genes and collagen-related genes. Importantly, the HA-LCS fillers not only stimulated the regeneration of mature blood vessels, but also promoted collagen secretion in dermal skin and filling area. This study not only presented an injectable filler with enhanced regeneration of blood vessels and collagen, but also provided a new strategy for developing tissue-induced fillers based on bioactive components of silicate bioceramics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532328","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}
Bioactive MaterialsPub Date : 2024-10-23DOI: 10.1016/j.bioactmat.2024.10.004
{"title":"Acid-responsive CST@NPs enhanced diabetic wound healing through rescuing mitochondrial dysfunction","authors":"","doi":"10.1016/j.bioactmat.2024.10.004","DOIUrl":"10.1016/j.bioactmat.2024.10.004","url":null,"abstract":"<div><div>Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats. This finding led us to hypothesize that the administration of exogenous CST is an effective strategy to promote wound healing in patients with DUs. We herein successfully prepared CST-loaded pDMA-pEPEMA nanoparticles (CST@NPs) designed to exhibit localized, acid-responsive behavior for enhanced wound healing. These CST@NPs were sensitive to acidic environments, triggering the rapid release of CST. <em>In vitro</em> experiments showed that CST@NPs effectively alleviated oxidative stress and reduced apoptosis in human umbilical vein endothelial cells (HUVECs). Our findings further demonstrated that CST@NPs accelerated re-epithelialization of the wound, enhanced collagen deposition, and stimulated angiogenesis, while alleviating the local inflammatory response. Both <em>in vivo</em> and <em>in vitro</em> results indicate that CST@NPs possess precise and rapid response capabilities in acidic environments, ensuring effective CST release to promote diabetic wound healing. In summary, this acid-responsive nanoparticle system presents a highly efficient therapeutic strategy for the treatment of chronic diabetic wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532329","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}
Bioactive MaterialsPub Date : 2024-10-23DOI: 10.1016/j.bioactmat.2024.10.017
{"title":"Extracellular Vesicles-in-Hydrogel (EViH) targeting pathophysiology for tissue repair","authors":"","doi":"10.1016/j.bioactmat.2024.10.017","DOIUrl":"10.1016/j.bioactmat.2024.10.017","url":null,"abstract":"<div><div>Regenerative medicine endeavors to restore damaged tissues and organs utilizing biological approaches. Utilizing biomaterials to target and regulate the pathophysiological processes of injured tissues stands as a crucial method in propelling this field forward. The Extracellular Vesicles-in-Hydrogel (EViH) system amalgamates the advantages of extracellular vesicles (EVs) and hydrogels, rendering it a prominent biomaterial in regenerative medicine with substantial potential for clinical translation. This review elucidates the development and benefits of the EViH system in tissue regeneration, emphasizing the interaction and impact of EVs and hydrogels. Furthermore, it succinctly outlines the pathophysiological characteristics of various types of tissue injuries such as wounds, bone and cartilage injuries, cardiovascular diseases, nerve injuries, as well as liver and kidney injuries, underscoring how EViH systems target these processes to address related tissue damage. Lastly, it explores the challenges and prospects in further advancing EViH-based tissue regeneration, aiming to impart a comprehensive understanding of EViH. The objective is to furnish a thorough overview of EViH in enhancing regenerative medicine applications and to inspire researchers to devise innovative tissue engineering materials for regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532330","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}
Bioactive MaterialsPub Date : 2024-10-23DOI: 10.1016/j.bioactmat.2024.10.016
{"title":"Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling","authors":"","doi":"10.1016/j.bioactmat.2024.10.016","DOIUrl":"10.1016/j.bioactmat.2024.10.016","url":null,"abstract":"<div><div>Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532334","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}
Bioactive MaterialsPub Date : 2024-10-22DOI: 10.1016/j.bioactmat.2024.10.015
{"title":"Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy","authors":"","doi":"10.1016/j.bioactmat.2024.10.015","DOIUrl":"10.1016/j.bioactmat.2024.10.015","url":null,"abstract":"<div><div>Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532281","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}
Bioactive MaterialsPub Date : 2024-10-21DOI: 10.1016/j.bioactmat.2024.09.015
{"title":"Development of an implantable sensor system for in vivo strain, temperature, and pH monitoring: comparative evaluation of titanium and resorbable magnesium plates","authors":"","doi":"10.1016/j.bioactmat.2024.09.015","DOIUrl":"10.1016/j.bioactmat.2024.09.015","url":null,"abstract":"<div><div>Biodegradable magnesium is a highly desired material for fracture fixation implants because of its good mechanical properties and ability to completely dissolve in the body over time, eliminating the need for a secondary surgery to remove the implant. Despite extensive research on these materials, there remains a dearth of information regarding critical factors that affect implant performance in clinical applications, such as the <em>in vivo</em> pH and mechanical loading conditions. We developed a measurement system with implantable strain, temperature, pH and motion sensors to characterize magnesium and titanium plates, fixating bilateral zygomatic arch osteotomies in three Swiss alpine sheep for eight weeks. pH 1–2 mm above titanium plates was 6.6 ± 0.4, while for magnesium plates it was slightly elevated to 7.4 ± 0.8. Strains on magnesium plates were higher than on titanium plates, possibly due to the lower Young's modulus of magnesium. One magnesium plate experienced excessive loading, which led to plate failure within 31 h. This is, to our knowledge, the first <em>in vivo</em> strain, temperature, and pH data recorded for magnesium implants used for fracture fixation. These results provide insight into magnesium degradation and its influence on the <em>in vivo</em> environment, and may help to improve material and implant design for future clinical applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535291","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}
Bioactive MaterialsPub Date : 2024-10-19DOI: 10.1016/j.bioactmat.2024.10.011
{"title":"Scaffolds functionalized with matrix metalloproteinase-responsive release of miRNA for synergistic magnetic hyperthermia and sensitizing chemotherapy of drug-tolerant breast cancer","authors":"","doi":"10.1016/j.bioactmat.2024.10.011","DOIUrl":"10.1016/j.bioactmat.2024.10.011","url":null,"abstract":"<div><div>Combining hyperthermia and chemotherapy for maximum anticancer efficacy remains a challenge because drug-tolerant cancer cells often evade this synergistic treatment due to drug resistance and asynchronous drug release. In this study, multifunctional scaffolds were designed to efficiently treat drug-tolerant breast cancer by improving the sensitization of breast cancer cells and synchronizing anticancer drug release with magnetic hyperthermia. The scaffolds contained microRNA-encapsulated matrix metalloproteinase-cleavable liposomes, doxorubicin-encapsulated thermoresponsive liposomes and Fe<sub>3</sub>O<sub>4</sub> nanoparticles. The scaffolds could release microRNA specifically to improve the sensitization of breast cancer cells to anticancer drugs. The scaffolds also showed excellent hyperthermia effects under alternating magnetic field irradiation. Moreover, doxorubicin release was synchronized with magnetic hyperthermia. <em>In vitro</em> and <em>in vivo</em> studies demonstrated that the scaffolds effectively reduced drug resistance and eliminated doxorubicin-tolerant MDA-MB-231 cells through the synergistic effect of magnetic hyperthermia and sensitizing chemotherapy. Additionally, the scaffolds could support the proliferation and adipogenic differentiation of stem cells for adipose tissue regeneration after killing cancer cells at a late therapeutic stage. These composite scaffolds offer an innovative strategy for treating breast cancer, with synergistic anticancer effects and regenerative functions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532279","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}
Bioactive MaterialsPub Date : 2024-10-19DOI: 10.1016/j.bioactmat.2024.10.013
{"title":"Injectable acellular matrix microgel assembly with stem cell recruitment and chondrogenic differentiation functions promotes microfracture-based articular cartilage regeneration","authors":"","doi":"10.1016/j.bioactmat.2024.10.013","DOIUrl":"10.1016/j.bioactmat.2024.10.013","url":null,"abstract":"<div><div>Articular cartilage repair and regeneration is still a significant challenge despite years of research. Although microfracture techniques are commonly used in clinical practice, the newborn cartilage is usually fibrocartilage rather than hyaline cartilage, which is mainly attributed to the inadequate microenvironment for effectively recruiting, anchoring, and inducing bone marrow mesenchymal stem cells (BMSCs) to differentiate into hyaline cartilage. This paper introduces a novel cartilage acellular matrix (CACM) microgel assembly with excellent microporosity, injectability, tissue adhesion, BMSCs recruitment and chondrogenic differentiation capabilities to improve the microfracture-based articular cartilage regeneration. Specifically, the sustained release of simvastatin (SIM) from the SIM@CACM microgel assembly efficiently recruits BMSCs in the early stage of cartilage regeneration, while the abundant interconnected micropores and high specific area assure the quick adhesion, proliferation and infiltration of BMSCs. Additionally, the active factors within the CACM matrix, appropriate mechanical properties of the microgel assembly, and excellent tissue adhesion provide a conductive environment for the continuous chondrogenic differentiation of BMSCs into hyaline cartilage. Owing to the synergistic effect of the above-mentioned factors, good articular cartilage repair and regeneration is achieved.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532280","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}
Bioactive MaterialsPub Date : 2024-10-18DOI: 10.1016/j.bioactmat.2024.10.010
{"title":"Engineering human immune organoids for translational immunology","authors":"","doi":"10.1016/j.bioactmat.2024.10.010","DOIUrl":"10.1016/j.bioactmat.2024.10.010","url":null,"abstract":"<div><div>Animal models have been extensively used as a gold standard in various biological research, including immunological studies. Despite high availability and ease of handling procedure, they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures. Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs. In this review, we describe the use of organoid system to overcome limitations in animal-based investigations, such as physiological mismatch with humans, costly, time-consuming, and low throughput screening. Immune organoids are one of the specific advancements in organogenesis <em>ex vivo</em>, which can reflect human adaptive immunity with more physiologically relevant aspects. We discuss how immune organoids are established from patient-derived lymphoid tissues, as well as their characteristics and functional features to understand immune mechanisms and responses. Also, some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446327","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}