{"title":"Genetically Modified Hepatocytes Targeting Bilirubin and Ammonia Metabolism for the Construction of Bioartificial Liver System.","authors":"Ke Wang, Yuankui Zhu, Mengqing Li, Yaxi Yang, Dianbao Zuo, Junfeng Sheng, Xinhai Zhang, Wei Wang, Ping Zhou, Mingqian Feng","doi":"10.34133/bmr.0043","DOIUrl":"10.34133/bmr.0043","url":null,"abstract":"<p><p>Acute liver failure (ALF) is a complex syndrome that impairs the liver's function to detoxify bilirubin, ammonia, and other toxic metabolites. Bioartificial liver (BAL) aims to help ALF patients to pass through the urgent period by temporarily undertaking the liver's detoxification functions and promoting the recovery of the injured liver. We genetically modified the hepatocellular cell line HepG2 by stably overexpressing genes encoding UGT1A1, OATP1B1, OTC, ARG1, and CPS1. The resulting SynHeps-II cell line, encapsulated by Cytopore microcarriers, dramatically reduced the serum levels of bilirubin and ammonia, as demonstrated both in vitro using patient plasma and in vivo using ALF animal models. More importantly, we have also completed the 3-dimensional (3D) culturing of cells to meet the demands for industrialized rapid and mass production, and subsequently assembled the plasma-cell contacting BAL (PCC-BAL) system to fulfill the requirements of preclinical experiments. Extracorporeal blood purification of ALF rabbits with SynHeps-II-embedded PCC-BAL saved more than 80% of the animals from rapid death. Mechanistically, SynHeps-II therapy ameliorated liver and brain inflammation caused by high levels of bilirubin and ammonia and promoted liver regeneration by modulating the nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Also, SynHeps-II treatment reduced cerebral infiltration of neutrophils, reduced reactive oxygen species (ROS) levels, and mitigated hepatic encephalopathy. Taken together, SynHeps-II cell-based BAL was promising for the treatment of ALF patients and warrants clinical trials.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0043"},"PeriodicalIF":8.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621975","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 : 2024-05-29eCollection Date: 2024-01-01DOI: 10.34133/bmr.0036
Hae Sang Park, Shinya Yokomizo, Haoran Wang, Sophia Manganiello, Hailey Monaco, Rose McDonnell, Hajin Joanne Kim, Jiyun Rho, Sung Ahn, Jason Gladstone, Harry Jung, Homan Kang, Kai Bao, Satoshi Kashiwagi, Hak Soo Choi
{"title":"Erratum to \"Bifunctional Tumor-Targeted Bioprobe for Phototheranosis\".","authors":"Hae Sang Park, Shinya Yokomizo, Haoran Wang, Sophia Manganiello, Hailey Monaco, Rose McDonnell, Hajin Joanne Kim, Jiyun Rho, Sung Ahn, Jason Gladstone, Harry Jung, Homan Kang, Kai Bao, Satoshi Kashiwagi, Hak Soo Choi","doi":"10.34133/bmr.0036","DOIUrl":"10.34133/bmr.0036","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.34133/bmr.0002.].</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0036"},"PeriodicalIF":8.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309359","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 : 2024-04-25eCollection Date: 2024-01-01DOI: 10.34133/bmr.0015
Zishuo Guo, Jinhong Ye, Xuehao Cheng, Tieshan Wang, Yi Zhang, Kaili Yang, Shouying Du, Pengyue Li
{"title":"Nanodrug Delivery Systems in Antitumor Immunotherapy.","authors":"Zishuo Guo, Jinhong Ye, Xuehao Cheng, Tieshan Wang, Yi Zhang, Kaili Yang, Shouying Du, Pengyue Li","doi":"10.34133/bmr.0015","DOIUrl":"10.34133/bmr.0015","url":null,"abstract":"<p><p>Cancer has become one of the most important factors threatening human health, and the global cancer burden has been increasing rapidly. Immunotherapy has become another clinical research hotspot after surgery, chemotherapy, and radiotherapy because of its high efficiency and tumor metastasis prevention. However, problems such as lower immune response rate and immune-related adverse reaction in the clinical application of immunotherapy need to be urgently solved. With the development of nanodrug delivery systems, various nanocarrier materials have been used in the research of antitumor immunotherapy with encouraging therapeutic results. In this review, we mainly summarized the combination of nanodrug delivery systems and immunotherapy from the following 4 aspects: (a) nanodrug delivery systems combined with cytokine therapy to improve cytokines delivery in vivo; (b) nanodrug delivery systems provided a suitable platform for the combination of immune checkpoint blockade therapy with other tumor treatments; (c) nanodrug delivery systems helped deliver antigens and adjuvants for tumor vaccines to enhance immune effects; and (d) nanodrug delivery systems improved tumor treatment efficiency and reduced toxicity for adoptive cell therapy. Nanomaterials chosen by researchers to construct nanodrug delivery systems and their function were also introduced in detail. Finally, we discussed the current challenges and future prospects in combining nanodrug delivery systems with immunotherapy.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0015"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11045275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263074","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 : 2024-03-28eCollection Date: 2024-01-01DOI: 10.34133/bmr.0012
Tausif Muhammad, Byungwook Park, Aseer Intisar, Minseok S Kim, Jin-Kyu Park, Sohee Kim
{"title":"An Ultrasoft and Flexible PDMS-Based Balloon-Type Implantable Device for Controlled Drug Delivery.","authors":"Tausif Muhammad, Byungwook Park, Aseer Intisar, Minseok S Kim, Jin-Kyu Park, Sohee Kim","doi":"10.34133/bmr.0012","DOIUrl":"10.34133/bmr.0012","url":null,"abstract":"<p><p>Non-biodegradable implants have undergone extensive investigation as drug delivery devices to enable advanced healthcare toward personalized medicine. However, fibroblast encapsulation is one of the major challenges in all non-biodegradable implants, besides other challenges such as high initial burst, risk of membrane rupture, high onset time, non-conformal contact with tissues, and tissue damage. To tackle such challenges, we propose a novel ultrasoft and flexible balloon-type drug delivery device for unidirectional and long-term controlled release. The ultrasoft balloon-type device (USBD) was fabricated by using selective bonding between 2 polydimethylsiloxane (PDMS) membranes and injecting a fluid into the non-bonded area between them. The balloon acted as a reservoir containing a liquid drug, and at the same time, the membrane of the balloon itself acted as the pathway for release based on diffusion. The release was modulated by tuning the thickness and composition of the PDMS membrane. Regardless of the thickness and composition, all devices exhibited zero-order release behavior. The longest zero-order release and nearly zero-order release were achieved for 30 days and 58 days at a release rate of 1.16 μg/day and 1.68 μg/day, respectively. In vivo evaluation was performed for 35 days in living rats, where the USBD maintained zero-order and nearly zero-order release for 28 days and 35 days, respectively. Thanks to the employment of ultrasoft and flexible membranes and device design, the USBD could achieve minimal tissue damage and foreign body responses. It is expected that the proposed device may provide a novel approach for long-term drug delivery with new therapeutic modalities.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0012"},"PeriodicalIF":8.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140338049","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":"Ferrous Selenide Stabilized Black Phosphorus Heterojunction Sonosensitizer for MR Imaging-Guided Sonodynamic Therapy of Bladder Cancer.","authors":"Sicheng Wu, Guanlin Li, Wenrui Ouyang, Yuan Tian, Shujue Li, Wenqi Wu, Hongxing Liu","doi":"10.34133/bmr.0014","DOIUrl":"10.34133/bmr.0014","url":null,"abstract":"<p><p>It is urgent to develop an alternative dynamic therapy-based method to overcome the limited efficacy of traditional therapy methods for bladder cancer and the damage caused to patients. Sonodynamic therapy (SDT) has the advantages of high tissue penetration, high spatiotemporal selectivity, and being non-invasive, representing an emerging method for eradicating deep solid tumors. However, the effectiveness of SDT is often hindered by the inefficient production of reactive oxygen species and the nondegradability of the sonosensitizer. To improve the anti-tumor effect of SDT on bladder cancer, herein, a BP-based heterojunction sonosensitizer (BFeSe<sub>2</sub>) was synthesized by anchoring FeSe<sub>2</sub> onto BP via P-Se bonding to enhance the stability and the effect of SDT. As a result, BFeSe<sub>2</sub> showed great cytotoxicity to bladder cancer cells under ultrasound (US) irradiation. BFeSe<sub>2</sub> led to a notable inhibition effect on tumor growth in subcutaneous tumor models and orthotopic tumor models under US irradiation. In addition, BFeSe<sub>2</sub> could also enhance T2-weighted magnetic resonance imaging (MRI) to achieve monitoring and guide treatment of bladder cancer. In general, BFeSe<sub>2</sub> sonosensitizer integrates MRI functions for precise treatment, promising great clinical potential for the theranostics of bladder cancer.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0014"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10976587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320061","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 : 2024-03-23eCollection Date: 2024-01-01DOI: 10.34133/bmr.0008
Hee Seung Seo, Jun-Hyeok Han, Jaesung Lim, Ga-Hyun Bae, Min Ji Byun, Chi-Pin James Wang, Jieun Han, Juwon Park, Hee Ho Park, Mikyung Shin, Tae-Eun Park, Tae-Hyung Kim, Se-Na Kim, Wooram Park, Chun Gwon Park
{"title":"Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.","authors":"Hee Seung Seo, Jun-Hyeok Han, Jaesung Lim, Ga-Hyun Bae, Min Ji Byun, Chi-Pin James Wang, Jieun Han, Juwon Park, Hee Ho Park, Mikyung Shin, Tae-Eun Park, Tae-Hyung Kim, Se-Na Kim, Wooram Park, Chun Gwon Park","doi":"10.34133/bmr.0008","DOIUrl":"10.34133/bmr.0008","url":null,"abstract":"<p><p><b>Background:</b> Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. <b>Methods:</b> In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. <b>Results:</b> This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. <b>Conclusions:</b> The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0008"},"PeriodicalIF":0.0,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295567","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 : 2024-03-15eCollection Date: 2024-01-01DOI: 10.34133/bmr.0011
Boram Son, Sora Park, Sungwoo Cho, Jeong Ah Kim, Seung-Ho Baek, Ki Hyun Yoo, Dongoh Han, Jinmyoung Joo, Hee Ho Park, Tai Hyun Park
{"title":"Improved Neural Inductivity of Size-Controlled 3D Human Embryonic Stem Cells Using Magnetic Nanoparticles.","authors":"Boram Son, Sora Park, Sungwoo Cho, Jeong Ah Kim, Seung-Ho Baek, Ki Hyun Yoo, Dongoh Han, Jinmyoung Joo, Hee Ho Park, Tai Hyun Park","doi":"10.34133/bmr.0011","DOIUrl":"10.34133/bmr.0011","url":null,"abstract":"<p><p><b>Background:</b> To improve the efficiency of neural development from human embryonic stem cells, human embryoid body (hEB) generation is vital through 3-dimensional formation. However, conventional approaches still have limitations: long-term cultivation and laborious steps for lineage determination. <b>Methods:</b> In this study, we controlled the size of hEBs for ectodermal lineage specification using cell-penetrating magnetic nanoparticles (MNPs), which resulted in reduced time required for initial neural induction. The magnetized cells were applied to concentrated magnetic force for magnet-derived multicellular organization. The uniformly sized hEBs were differentiated in neural induction medium (NIM) and suspended condition. This neurally induced MNP-hEBs were compared with other groups. <b>Results:</b> As a result, the uniformly sized MNP-hEBs in NIM showed significantly improved neural inductivity through morphological analysis and expression of neural markers. Signaling pathways of the accelerated neural induction were detected via expression of representative proteins; Wnt signaling, dopaminergic neuronal pathway, intercellular communications, and mechanotransduction. Consequently, we could shorten the time necessary for early neurogenesis, thereby enhancing the neural induction efficiency. <b>Conclusion:</b> Overall, this study suggests not only the importance of size regulation of hEBs at initial differentiation stage but also the efficacy of MNP-based neural induction method and stimulations for enhanced neural tissue regeneration.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0011"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159692","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 : 2024-03-07eCollection Date: 2024-01-01DOI: 10.34133/bmr.0010
Gyuho Choi, Hyunkoo Kang, Jung-Soo Suh, Haksoo Lee, Kiseok Han, Gaeun Yoo, Hyejin Jo, Yeong Min Shin, Tae-Jin Kim, BuHyun Youn
{"title":"Novel Estrogen Receptor Dimerization BRET-Based Biosensors for Screening Estrogenic Endocrine-Disrupting Chemicals.","authors":"Gyuho Choi, Hyunkoo Kang, Jung-Soo Suh, Haksoo Lee, Kiseok Han, Gaeun Yoo, Hyejin Jo, Yeong Min Shin, Tae-Jin Kim, BuHyun Youn","doi":"10.34133/bmr.0010","DOIUrl":"10.34133/bmr.0010","url":null,"abstract":"<p><p>The increasing prevalence of endocrine-disrupting chemicals (EDCs) in our environment is a growing concern, with numerous studies highlighting their adverse effects on the human endocrine system. Among the EDCs, estrogenic endocrine-disrupting chemicals (eEDCs) are exogenous compounds that perturb estrogenic hormone function by interfering with estrogen receptor (ER) homo (α/α, β/β) or hetero (α/β) dimerization. To date, a comprehensive screening approach for eEDCs affecting all ER dimer forms in live cells is lacking. Here, we developed ER dimerization-detecting biosensors (ERDDBs), based on bioluminescence resonance energy transfer, for dimerization detection and rapid eEDC identification. To enhance the performance of these biosensors, we determined optimal donor and acceptor locations using computational analysis. Additionally, employing HaloTag as the acceptor and incorporating the P2A peptide as a linker yielded the highest sensitivity among the prototypes. We also established stable cell lines to screen potential ER dimerization inducers among estrogen analogs (EAs). The EAs were categorized through cross-comparison of ER dimer responses, utilizing EC values derived from a standard curve established with 17β-estradiol. We successfully classified 26 of 72 EAs, identifying which ER dimerization types they induce. Overall, our study underscores the effectiveness of the optimized ERDDB for detecting ER dimerization and its applicability in screening and identifying eEDCs.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0010"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10923609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095323","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 : 2024-03-04eCollection Date: 2024-01-01DOI: 10.34133/bmr.0007
Hye Ran Jeon, Jeon Il Kang, Suk Ho Bhang, Kyung Min Park, Dong-Ik Kim
{"title":"Transplantation of Stem Cell Spheroid-Laden 3-Dimensional Patches with Bioadhesives for the Treatment of Myocardial Infarction.","authors":"Hye Ran Jeon, Jeon Il Kang, Suk Ho Bhang, Kyung Min Park, Dong-Ik Kim","doi":"10.34133/bmr.0007","DOIUrl":"10.34133/bmr.0007","url":null,"abstract":"<p><p>Myocardial infarction (MI) is treated with stem cell transplantation using various biomaterials and methods, such as stem cell/spheroid injections, cell sheets, and cardiac patches. However, current treatment methods have some limitations, including low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage to heart due to injection and suturing to immobilize them in the heart, inducing side effects. In this study, we developed stem cell spheroid-laden 3-dimensional (3D) patches (S_3DP) with biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. The spheroids formed within S_3DP showed increased viability and expression of angiogenic factors compared to 2-dimensional cultured cells. We also fabricated gelatin-based tissue adhesive biosealants via a thiol-ene reaction and disulfide bond formation. This biosealant showed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing in vivo, thereby improving cardiac function and reducing heart fibrosis. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0007"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029728","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 : 2024-03-04eCollection Date: 2024-01-01DOI: 10.34133/bmr.0006
Pengcheng Tu, Yalan Pan, Lining Wang, Bin Li, Xiaoxian Sun, Zhongqing Liang, Mengmin Liu, Zitong Zhao, Chengjie Wu, Jianwei Wang, Zhifang Wang, Yu Song, Yafeng Zhang, Yong Ma, Yang Guo
{"title":"CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis.","authors":"Pengcheng Tu, Yalan Pan, Lining Wang, Bin Li, Xiaoxian Sun, Zhongqing Liang, Mengmin Liu, Zitong Zhao, Chengjie Wu, Jianwei Wang, Zhifang Wang, Yu Song, Yafeng Zhang, Yong Ma, Yang Guo","doi":"10.34133/bmr.0006","DOIUrl":"10.34133/bmr.0006","url":null,"abstract":"<p><p><b>Background:</b> In the environment of cartilage injury, the activation of vascular endothelial cell (VEC), marked with excessive CD62E and reactive oxygen species (ROS), can affect the formation of hyaluronic cartilage. Therefore, we developed a CD62E- and ROS-responsive drug delivery system using E-selectin binding peptide, Thioketal, and silk fibroin (ETS) to achieve targeted delivery and controlled release of Clematis triterpenoid saponins (CS) against activated VEC, and thus promote cartilage regeneration. <b>Methods:</b> We prepared and characterized ETS/CS and verified their CD62E- and ROS-responsive properties in vitro. We investigated the effect and underlying mechanism of ETS/CS on inhibiting VEC activation and promoting chondrogenic differentiation of bone marrow stromal cells (BMSCs). We also analyzed the effect of ETS/CS on suppressing the activated VEC-macrophage inflammatory cascade in vitro. Additionally, we constructed a rat knee cartilage defect model and administered ETS/CS combined with BMSC-containing hydrogels. We detected the cartilage differentiation, the level of VEC activation and macrophage in the new tissue, and synovial tissue. <b>Results:</b> ETS/CS was able to interact with VEC and inhibit VEC activation through the carried CS. Coculture experiments verified ETS/CS promoted chondrogenic differentiation of BMSCs by inhibiting the activated VEC-induced inflammatory cascade of macrophages via OPA1-mediated mitochondrial homeostasis. In the rat knee cartilage defect model, ETS/CS reduced VEC activation, migration, angiogenesis in new tissues, inhibited macrophage infiltration and inflammation, promoted chondrogenic differentiation of BMSCs in the defective areas. <b>Conclusions:</b> CD62E- and ROS-responsive ETS/CS promoted cartilage repair by inhibiting VEC activation and macrophage inflammation and promoting BMSC chondrogenesis. Therefore, it is a promising therapeutic strategy to promote articular cartilage repair.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0006"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029727","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}