Biomaterials researchPub Date : 2024-09-11eCollection Date: 2024-01-01DOI: 10.34133/bmr.0070
Jeong-Won Lee, Jung-Ah Cho, Yoo Jin Roh, Min Ae Han, Je-Un Jeong, Sivakumar Allur Subramanian, Eunho Kang, Jiwoo Yeom, Chang-Hun Lee, Sung Jae Kim
{"title":"Antibacterial Immunonegative Coating with Biocompatible Materials on a Nanostructured Titanium Plate for Orthopedic Bone Fracture Surgery.","authors":"Jeong-Won Lee, Jung-Ah Cho, Yoo Jin Roh, Min Ae Han, Je-Un Jeong, Sivakumar Allur Subramanian, Eunho Kang, Jiwoo Yeom, Chang-Hun Lee, Sung Jae Kim","doi":"10.34133/bmr.0070","DOIUrl":"https://doi.org/10.34133/bmr.0070","url":null,"abstract":"<p><p>Periprosthetic infections resulting from bacterial biofilm formation following surgical bone fracture fixation present important clinical challenges. Conventional orthopedic implant materials, such as titanium, are prone to biofilm formation. This study introduces a novel surface for orthopedic titanium plates, optimized for clinical application in human bone fractures. Leveraging nanostructure-based surface coating technology, the plate achieves an antibacterial/immunonegative surface using biocompatible materials, including poloxamer 407, epigallocatechin gallate, and octanoic acid. These materials demonstrate high biocompatibility and thermal stability after autoclaving. The developed plate, named antibacterial immunonegative surface, releases antibacterial agents and prevents adhesion between human tissue and metal surfaces. Antibacterial immunonegative surface plates exhibit low cell toxicity, robust antibacterial effects against pathogens such as <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, high resistance to biofilm formation on the implant surface and surrounding tissues, and minimal immune reaction in a rabbit femoral fracture model. This innovation holds promise for addressing periprosthetic infections and improving the performance of orthopedic implants.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0070"},"PeriodicalIF":8.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303311","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":"Nanoarchitectonics of Injectable Biomimetic Conjugates for Cartilage Protection and Therapy Based on Degenerative Osteoarthritis Progression.","authors":"Jingwei Bi, Limin Zhang, Pengfei Zhang, Shulei Xu, Yuhao Liu, Xiaolai Zhang, Xiaoyong Qiu, Yanwen Bi, Fangfang Yan, Hui Wei, Xin Cui, Xin Pan, Jun Huang, Yunpeng Zhao","doi":"10.34133/bmr.0075","DOIUrl":"https://doi.org/10.34133/bmr.0075","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common age-related degenerative disease characterized by changes in the local tissue environment as inflammation progresses. Inspired by the wind-dispersal mechanism of dandelion seeds, this study develops responsive biomimetic microsphere-drug conjugate for OA therapy and protection. The conjugate integrates dibenzaldehyde polyethylene glycol (DFPEG) with chitosan and polyethylene glycol diacrylate (PEGDA) through dynamic covalent bonds to form a dual-network hydrogel microsphere. Based on the progression of OA, the conjugate with the surface-anchored cyclic peptide cortistatin-14 (CST-14) achieves targeted drug therapy and a self-regulating hydrogel network. In cases of progressing inflammation (pH < 5), CST-14 dissociates from the microsphere surface (viz. the drug release rate increased) and inhibits TNF-α signaling to suppress OA. Concurrently, the monomer DFPEG responsively detaches from the hydrogel network and scavenges reactive oxygen species (ROS) to protect the cartilage tissue. The ROS scavenging of DFPEG is comparable to that of coenzyme Q10 and vitamin C. The degraded PEGDA microspheres provide tissue lubrication through reused conjugates. The rat OA model successfully achieved a synergistic therapeutic effect greater than the additive effect (1 + 1 > 2). This strategy offers an approach for anchoring amine-containing drugs and has marked potential for OA treatment and protection.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0075"},"PeriodicalIF":8.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303317","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}
Biomaterials researchPub Date : 2024-09-09eCollection Date: 2024-01-01DOI: 10.34133/bmr.0076
Yang Luo, Zeming Hu, Renhao Ni, Rong Xu, Jianmin Zhao, Peipei Feng, Tong Zhu, Yaoqi Chen, Jie Yao, Yudong Yao, Lu Yang, Hua Zhang, Yabin Zhu
{"title":"Fabrication of 3D Biomimetic Smooth Muscle Using Magnetic Induction and Bioprinting for Tissue Regeneration.","authors":"Yang Luo, Zeming Hu, Renhao Ni, Rong Xu, Jianmin Zhao, Peipei Feng, Tong Zhu, Yaoqi Chen, Jie Yao, Yudong Yao, Lu Yang, Hua Zhang, Yabin Zhu","doi":"10.34133/bmr.0076","DOIUrl":"https://doi.org/10.34133/bmr.0076","url":null,"abstract":"<p><p>Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe<sub>3</sub>O<sub>4</sub>) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe<sub>3</sub>O<sub>4</sub> self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0076"},"PeriodicalIF":8.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303314","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}
Biomaterials researchPub Date : 2024-09-06eCollection Date: 2024-01-01DOI: 10.34133/bmr.0073
Lei Liu, Gang He, Yixi Li, Yiwen Xian, Guixian He, Yonglong Hong, Chong Zhang, Decheng Wu
{"title":"Hyaluronic Acid-Based Microparticles with Lubrication and Anti-Inflammation for Alleviating Temporomandibular Joint Osteoarthritis.","authors":"Lei Liu, Gang He, Yixi Li, Yiwen Xian, Guixian He, Yonglong Hong, Chong Zhang, Decheng Wu","doi":"10.34133/bmr.0073","DOIUrl":"10.34133/bmr.0073","url":null,"abstract":"<p><p>The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) is closely associated with mechanical friction, which leads to the up-regulation of inflammatory mediators and the degradation of articular cartilage. Injectable drug-loaded microparticles have attracted widespread interest in intra-articular treatment of TMJOA by providing lubrication and facilitating localized drug delivery. Herein, a hyaluronic acid-based microparticle is developed with excellent lubrication properties, drug loading capacity, antioxidant activity, and anti-inflammatory effect for the treatment of TMJOA. The microparticles are facilely prepared by the self-assembly of 3-aminophenylboronic acid-modified hyaluronic acid (HP) through hydrophobic interaction in an aqueous solution, which can further encapsulate diol-containing drugs through dynamic boronate ester bonds. The resulting microparticles demonstrate excellent injectability, lubrication properties, radical scavenging efficiency, and antibacterial activity. Additionally, the drug-loaded microparticles exhibit a favorable cytoprotective effect on chondrocyte cells in vitro under an oxidative stress microenvironment. In vivo experiments validate that intra-articular injection of drug-loaded microparticles effectively alleviates osteoporosis-like damage, suppresses inflammatory response, and facilitates matrix regeneration in the treatment of TMJOA. The HP microparticles demonstrate excellent injectability and encapsulation capacity for diol-containing drugs, highlighting its potential as a versatile drug delivery vehicle in the intra-articular treatment of TMJOA.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0073"},"PeriodicalIF":8.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156935","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":"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}
Biomaterials researchPub Date : 2024-09-06eCollection Date: 2024-01-01DOI: 10.34133/bmr.0074
Shiguo Yuan, Boyuan Zheng, Kai Zheng, Zhiheng Lai, Zihang Chen, Jing Zhao, Shaoping Li, Xiaofei Zheng, Peng Wu, Huajun Wang
{"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, Ca<sup>2+</sup> and Si<sup>4+</sup> 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}
Biomaterials researchPub Date : 2024-08-30eCollection Date: 2024-01-01DOI: 10.34133/bmr.0072
Zhen Zhang, Xu Hu, Min Jin, Yulei Mu, Huiqun Zhou, Cheng Ma, Liang Ma, Bangheng Liu, Hang Yao, Ye Huang, Dong-An Wang
{"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}
Biomaterials researchPub Date : 2024-08-15eCollection Date: 2024-01-01DOI: 10.34133/bmr.0067
Janine Waletzko-Hellwig, Jan-Oliver Sass, Rainer Bader, Bernhard Frerich, Michael Dau
{"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/cm<sup>2</sup>. 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}
Biomaterials researchPub Date : 2024-08-02eCollection Date: 2024-01-01DOI: 10.34133/bmr.0050
Pengcheng Zhou, Xian'guang Ding, Xuanlong Du, Lianhui Wang, Yewei Zhang
{"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<sup>-148a</sup>), 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<sup>-148a</sup> effectively suppressed the proliferation and migration of pancreatic CAFs by targeting ITGA5 through the TGF-β/SMAD pathway. ITGA5-EVs<sup>-148a</sup> was associated with enhanced cellular uptake and exhibited enhanced in vitro and in vivo targeting ability. Moreover, ITGA5-EVs<sup>-148a</sup> 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<sup>-148a</sup> 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}