Biomaterials research最新文献

{"title":"Decellularized Extracellular Matrix Scaffolds for Soft Tissue Augmentation: From Host-Scaffold Interactions to Bottlenecks in Clinical Translation.","authors":"Yasamin Ostadi, Javad Khanali, Fatemeh A Tehrani, Ghasem Yazdanpanah, Soheyl Bahrami, Feizollah Niazi, Hassan Niknejad","doi":"10.34133/bmr.0071","DOIUrl":"10.34133/bmr.0071","url":null,"abstract":"<p><p>Along with a paradigm shift in looking at soft tissue fillers from space-filling to bioactive materials, decellularized extracellular matrix (DEM) fillers have gained more attention considering their superior bioactivity. However, the complex mechanisms that govern the interaction between host tissues and DEMs have been partially understood. This review first covers the mechanisms that determine immunogenicity, angiogenesis and vasculogenesis, and recellularization and remodeling after DEM implantation into host tissue, with a particular focus on related findings from filler materials. Accordingly, the review delves into the dual role of macrophages and their M1/M2 polarization paradigm to form both constructive and destructive immune responses to DEM implants. Moreover, the contribution of macrophages in angiogenesis has been elucidated, which includes but is not limited to the secretion of angiogenic growth factors and extracellular matrix (ECM) remodeling. The findings challenge the traditional view of immune cells as solely destructive entities in biomaterials and indicate their multifaceted roles in tissue regeneration. Furthermore, the review discusses how the compositional factors of DEMs, such as the presence of growth factors and matrikines, can influence angiogenesis, cell fate, and differentiation during the recellularization process. It is also shown that the biomechanical properties of DEMs, including tissue stiffness, modulate cell responses through mechanotransduction pathways, and the structural properties of DEMs, such as scaffold porosity, impact cell-cell and cell-ECM interactions. Finally, we pointed out the current clinical applications, the bottlenecks in the clinical translation of DEM biomaterials into soft tissue fillers, as well as the naïve research areas of the field.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0071"},"PeriodicalIF":8.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoregulation in Skull Defect Repair with a Smart Hydrogel Loaded with Mesoporous Bioactive Glasses.","authors":"Shiguo Yuan, Boyuan Zheng, Kai Zheng, Zhiheng Lai, Zihang Chen, Jing Zhao, Shaoping Li, Xiaofei Zheng, Peng Wu, Huajun Wang","doi":"10.34133/bmr.0074","DOIUrl":"10.34133/bmr.0074","url":null,"abstract":"<p><p>Skull defect repair is a complex and critical medical challenge, and there is an urgent need to develop multifunctional tissue engineering scaffolds for skull regeneration. The success of bone tissue engineering depends on the construction of scaffolds that can regulate the immune microenvironment of bone regeneration and mimic the liquid crystal and viscoelastic properties of natural bone extracellular matrix. Hence, a smart hydrogel (PEGDA5/AM15/CLC-BMP-4@MBG) with good biocompatibility and the ability to modulate the wound immune microenvironment has been developed for the repair of skull defects. The hydrogel consists of chitin liquid crystal hydrogel (PEGDA5/AM15/CLC) and mesoporous bioactive glasses (MBGs) loaded with bone morphogenetic protein-4 (BMP-4). The liquid crystal hydrogel not only offers the necessary biological support and mechanical properties but also maintains the stability of the liquid crystal state, facilitating adhesion and regeneration of surrounding bone tissue. In addition, BMP-4@MBG intelligently regulates the release rate of BMP-4 in response to changes in wound microenvironment, thus effectively promoting the transformation of macrophages from M1 to M2 macrophages. At the same time, Ca²⁺ and Si⁴⁺ released by MBG degradation and BMP-4 synergically promote bone repair process. The PEGDA5/AM15/CLC-BMP-4@MBG hydrogel shows excellent immunomodulatory and osteogenic properties of bone microenvironment and is a promising scaffold material for bone tissue engineering.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0074"},"PeriodicalIF":8.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wash-Free Bacterial Gram-Typing and Photodynamic Inactivation with Long-Chain-Tailed BODIPY Derivatives.","authors":"Yuefeng Ji, Jigai Li, Chunping Chen, Chunxiang Piao, Xin Zhou, Juyoung Yoon","doi":"10.34133/bmr.0069","DOIUrl":"10.34133/bmr.0069","url":null,"abstract":"<p><p>The rapid identification of bacterial Gram types and their viability, as well as efficient bacterial elimination are crucial for managing bacterial infections yet present important challenges. In this research, we utilized long-chain-tailed BODIPY derivatives to address these hurdles. Our data indicated that these derivatives can distinguish bacteria types and their viability in aqueous solutions through a concise turn-on fluorescent response. Among them, <b>B-8</b> stained both live and dead bacteria, and <b>B-14</b> offered a wash-free staining. <b>B-18</b> demonstrated the highest affinity to selectively fluorescent label viable gram-positive bacteria with a 53.2-fold fluorescent enhancement. Confocal imaging confirmed that <b>B-18</b> can serve as an effective membrane-specific probe for facilitating the typing between gram-negative and gram-positive bacteria in a wash-free manner. Additionally, <b>B-18</b> displayed selective photodynamic inactivation at 1 μM toward gram-positive bacteria. In vivo studies variformed the ideal photodynamic therapeutic efficacy of <b>B-18</b> against methicillin-resistant <i>Staphylococcus aureus</i> in mice wound infections.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0069"},"PeriodicalIF":8.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen Type II-Based Injectable Materials for In situ Repair and Regeneration of Articular Cartilage Defect.","authors":"Zhen Zhang, Xu Hu, Min Jin, Yulei Mu, Huiqun Zhou, Cheng Ma, Liang Ma, Bangheng Liu, Hang Yao, Ye Huang, Dong-An Wang","doi":"10.34133/bmr.0072","DOIUrl":"10.34133/bmr.0072","url":null,"abstract":"<p><p>Repairing and regenerating articular cartilage defects (ACDs) have long been challenging for physicians and scientists. The rise of injectable materials provides a novel strategy for minimally invasive surgery to repair ACDs. In this study, we successfully developed injectable materials based on collagen type II, achieving hyaline cartilage repair and regeneration of ACDs. Analysis was conducted on the regenerated cartilage after materials injection. The histology staining demonstrated complete healing of the ACDs with the attainment of a hyaline cartilage phenotype. The biochemical and biomechanical properties are similar to the adjacent native cartilage without noticeable adverse effects on the subchondral bone. Further transcriptome analysis found that compared with the Native cartilage adjacent to the defect area, the Regenerated cartilage in the defect area repaired with type II collagen-based injection materials showed changes in cartilage-related pathways, as well as down-regulation of T cell receptor signaling pathways and interleukin-17 signaling pathways, which changed the immune microenvironment of the ACD area. Overall, these findings offer a promising injectable approach to treating ACDs, providing a potential solution to the challenges associated with achieving hyaline cartilage in situ repair and regeneration while minimizing damage to the surrounding cartilage.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0072"},"PeriodicalIF":8.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Integrity of Allogeneic Bone Processed with High Hydrostatic Pressure: A Pilot Animal Study.","authors":"Janine Waletzko-Hellwig, Jan-Oliver Sass, Rainer Bader, Bernhard Frerich, Michael Dau","doi":"10.34133/bmr.0067","DOIUrl":"10.34133/bmr.0067","url":null,"abstract":"<p><p>Processing of bone allografts with strong acids and γ-sterilization results in decreased biomechanical properties and reduction in osteogenecity and osteoconductivity. High hydrostatic pressure (HHP) treatment could be a gentle alternative to processing techniques usually applied. HHP is known to induce devitalization of cancellous bone while preserving biomechanical stability and molecules that induce cell differentiation. Here, a specific HHP protocol for devitalization of cancellous bone was applied to rabbit femoral bone. Allogeneic bone cylinders were subsequently implanted into a defect in the lateral condyles of rabbit femora and were compared to autologous bone grafts. Analysis of bone integration 4 and 12 weeks postoperatively revealed no differences between autografts and HHP-treated allografts regarding the expression of genes characteristic for bone remodeling, showing expression niveous comparable to original bone cylinder. Furthermore, biomechanical properties were evaluated 12 weeks postoperatively. Autografts and HHP-treated allografts both showed a yield strength ranging between 2 and 2.5 MPa and an average bone mass density of 250 mg/cm². Furthermore, histological analysis of the region of interest revealed a rate of 5 to 10% BPM-2 and approximately 40% osteocalcin-positive staining, with no marked differences between allografts and autografts demonstrating comparable matrix deposition in the graft region. A suitable graft integrity was pointed out by μCT imaging in both groups, supporting the biomechanical data. In summary, the integrity of HHP-treated cancellous bone allografts showed similar results to untreated autografts. Hence, HHP treatment may represent a gentle and effective alternative to existing processing techniques for bone allografts.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0067"},"PeriodicalIF":8.1,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Reprogrammed Cancer-Associated Fibroblasts with Engineered Mesenchymal Stem Cell Extracellular Vesicles for Pancreatic Cancer Treatment.","authors":"Pengcheng Zhou, Xian'guang Ding, Xuanlong Du, Lianhui Wang, Yewei Zhang","doi":"10.34133/bmr.0050","DOIUrl":"10.34133/bmr.0050","url":null,"abstract":"<p><p><b>Background:</b> As one of the most aggressive and lethal cancers, pancreatic cancer is highly associated with cancer-associated fibroblasts (CAFs) that influence the development and progression of cancer. Targeted reprogramming of CAFs may be a promising strategy for pancreatic cancer. This study aims to construct engineered extracellular vesicles (EVs) with surface modification of integrin α5 (ITGA5)-targeting peptide and high internal expression of miR-148a-3p by endogenous modification for targeted reprogramming of pancreatic CAFs. <b>Methods:</b> Bone marrow mesenchymal stem cells (BMSCs) and pancreatic CAFs were cocultured to examine the effect of BMSC-derived EVs on the expression levels of CAF markers. miR-148a-3p was identified as a functional molecule. The mechanism of miR-148a-3p was elucidated using the dual-luciferase reporter assay. BMSCs were infected with TERT-encoding and miR-148a-3p-encoding lentiviruses. Subsequently, BMSCs were modified with ITGA5-specific targeting peptide. The supernatant was ultracentrifuged to obtain the engineered EVs (ITGA5-EVs^-148a), which were used to reprogram CAFs. <b>Results:</b> BMSCs modulated CAF marker expressions through EVs. miR-148a-3p was up-regulated in BMSCs. The expression of miR-148a-3p in pancreatic CAFs was down-regulated when compared with that in normal fibroblasts (NFs). Mechanistically, ITGA5-EVs^-148a effectively suppressed the proliferation and migration of pancreatic CAFs by targeting ITGA5 through the TGF-β/SMAD pathway. ITGA5-EVs^-148a was associated with enhanced cellular uptake and exhibited enhanced in vitro and in vivo targeting ability. Moreover, ITGA5-EVs^-148a exerted strong reconfiguration effects in inactivating CAFs and reversing tumor-promoting effects in 3D heterospheroid and xenograft pancreatic cancer models. <b>Conclusions:</b> This targeted CAF reprogramming strategy with genetically engineered ITGA5-EVs^-148a holds great promise as a precision therapeutics in clinical settings.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0050"},"PeriodicalIF":8.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Lipopeptide-Functionalized Metal-Organic Framework for Periodontitis Therapy through the Htra1/FAK/YAP Pathway.","authors":"Xuechun Wang, Qing Wang, Jian Wang, Xuan Wang, Linling Yin, Changping Wang, Guangjian Fan, Jinsong Pan","doi":"10.34133/bmr.0057","DOIUrl":"10.34133/bmr.0057","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C₁₀-KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C₁₀-KR8@ZIF-8 (C₁₀-KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C₁₀-KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C₁₀-KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C₁₀-KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C₁₀-KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0057"},"PeriodicalIF":8.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Membrane Fixation and the Graft Combinations on Horizontal Bone Regeneration: Radiographic and Histologic Outcomes in a Canine Model.","authors":"Jeong-Won Paik, Yoon-Hee Kwon, Jin-Young Park, Ronald E Jung, Ui-Won Jung, Daniel S Thoma","doi":"10.34133/bmr.0055","DOIUrl":"10.34133/bmr.0055","url":null,"abstract":"<p><p>The aim of this study was to determine the effect of membrane fixation and combinations of bone substitute materials and barrier membranes on horizontal bone regeneration in peri-implant defects. Eight mongrel dogs underwent chronic buccal peri-implant dehiscence defects creation and were randomized into 4 groups: (a) deproteinized bovine bone mineral 1 (DBBM1) with a native collagen membrane (CM) (BB group, positive control group), (b) DBBM1 with native CM and 2 fixation pins (BBP group), (c) DBBM2 with a cross-linked CM (XC group), and (d) DBBM2 with cross-linked CM and 2 fixation pins (XCP group). Following 16 weeks of healing, tissues were radiographically and histomorphometrically analyzed. The total augmented area was significantly larger in the BBP, XC, and XCP groups compared to the BB group (4.27 ± 3.21, 7.17 ± 7.23, and 6.91 ± 5.45 mm² versus 1.35 ± 1.28 mm², respectively; <i>P</i> = 0.022). No significant difference for the augmented tissue thickness was observed among the 4 groups. The augmented tissue thickness measured at 3 mm below the implant shoulder was higher in BBP, XC, and XCP than that in BB (2.43 ± 1.53, 2.62 ± 1.80, and 3.18 ± 1.96 mm versus 0.80 ± 0.90 mm, respectively), trending toward significance (<i>P</i> = 0.052). DBBM2 and a cross-linked CM were significantly more favorable for horizontal bone regeneration compared to DBBM1 and a native CM. However, when DBBM1 and a native CM were secured with fixation pins, outcomes were similar. The addition of pins did not lead to more favorable outcomes when a cross-linked CM was used.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0055"},"PeriodicalIF":8.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic Marine-Sponge-Derived Spicule-Microparticle-Mediated Biomineralization and YAP/TAZ Pathway for Bone Regeneration In Vivo.","authors":"Sumi Choi, Jung Hun Kim, Tae Hoon Kang, Young-Hyeon An, Sang Jin Lee, Nathaniel S Hwang, Su-Hwan Kim","doi":"10.34133/bmr.0056","DOIUrl":"10.34133/bmr.0056","url":null,"abstract":"<p><p>Marine-sponge-derived spicule microparticles (SPMs) possess unique structural and compositional features suitable for bone tissue engineering. However, significant challenges remain in establishing their osteogenic mechanism and practical application in animal models. This study explores the biomimetic potential of SPM in orchestrating biomineralization behavior and modulating the Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) pathway both in vitro and in vivo. Characterization of SPM revealed a structure comprising amorphous silica oxide mixed with collagen and trace amounts of calcium and phosphate ions, which have the potential to facilitate biomineralization. Structural analysis indicated dynamic biomineralization from SPM to hydroxyapatite, contributing to both in vitro and in vivo osteoconductions. In vitro assessment demonstrated dose-dependent increases in osteogenic gene expression and bone morphogenetic protein-2 protein in response to SPM. In addition, focal adhesion mediated by silica diatoms induced cell spreading on the surface of SPM, leading to cell alignment in the direction of SPM. Mechanical signals from SPM subsequently increased the expression of YAP/TAZ, thereby inducing osteogenic mechanotransduction. The osteogenic activity of SPM-reinforced injectable hydrogel was evaluated in a mouse calvaria defect model, demonstrating rapid vascularized bone regeneration. These findings suggest that biomimetic SPM holds significant promise for regenerating bone tissue.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0056"},"PeriodicalIF":8.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Central Nervous System Drug Delivery with Microtubule-Dependent Transcytosis of Novel Aqueous Compounds.","authors":"Mingzhu Zhang, Shaoqi Zhong, Lujing An, Pan Xiang, Na Hu, Wei Huang, Yupeng Tian, Giuseppe Battaglia, Xiaohe Tian, Min Wu","doi":"10.34133/bmr.0051","DOIUrl":"https://doi.org/10.34133/bmr.0051","url":null,"abstract":"<p><p>The challenge of delivering therapeutics to the central nervous system due to the restrictive nature of the blood-brain barrier (BBB) is a substantial hurdle in neuropharmacology. Our research introduces a breakthrough approach using microtubule-dependent transcytosis facilitated by novel aqueous compounds. We synthesized a series of red-emitting pyran nitrile derivatives. The molecular structure of compounds, photophysical properties, and water solubility were characterized. BBB permeability of BN1 was assessed in an in vitro BBB model. The transmembrane transport mechanism was next analyzed. The derivative was injected in the wild-type mouse for evaluation of brain penetration and biodistribution in the brain. We further investigated the potential of BN1-functionalized BBB-nonpenetrated silica nanoparticles for brain targeting. This compound demonstrated an ability to form endosomes within the phospholipid layer, thus enabling efficient penetration of the BBB via microtubule-mediated transcytosis, as evidenced in vitro model. This was further confirmed by in vivo experiments that BN1 displays the excellent BBB penetration and retained in brain parenchyma. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that our designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable new strategy for central-nervous-system-targeted drug delivery.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0051"},"PeriodicalIF":8.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}