Daniel P. Howsmon, Matthew F. Mikulski, Nikhil Kabra, Joyce Northrup, Daniel Stromberg, Charles D. Fraser Jr, Carlos M. Mery, Richard P. Lion
{"title":"Statistical process monitoring creates a hemodynamic trajectory map after pediatric cardiac surgery: A case study of the arterial switch operation","authors":"Daniel P. Howsmon, Matthew F. Mikulski, Nikhil Kabra, Joyce Northrup, Daniel Stromberg, Charles D. Fraser Jr, Carlos M. Mery, Richard P. Lion","doi":"10.1002/btm2.10679","DOIUrl":"10.1002/btm2.10679","url":null,"abstract":"<p>Postoperative critical care management of congenital heart disease patients requires prompt intervention when the patient deviates significantly from clinician-determined vital sign and hemodynamic goals. Current monitoring systems only allow for static thresholds to be set on individual variables, despite the expectations that these signals change as the patient recovers and that variables interact. To address this incongruency, we have employed statistical process monitoring (SPM) techniques originally developed to monitor batch industrial processes to monitor high-frequency vital sign and hemodynamic data to establish multivariate trajectory maps for patients with d-transposition of the great arteries following the arterial switch operation. In addition to providing multivariate trajectory maps, the multivariate control charts produced by the SPM framework allow for assessment of adherence to the desired trajectory at each time point as the data is collected. Control charts based on slow feature analysis were compared with those based on principal component analysis. Alarms generated by the multivariate control charts are discussed in the context of the available clinical documentation.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molly K. Grun, Praveen Honhar, Yazhe Wang, Samantha Rossano, Minsoo Khang, Hee Won Suh, Krista Fowles, Harvey J. Kliman, Alessandra Cavaliere, Richard E. Carson, Bernadette Marquez-Nostra, W. Mark Saltzman
{"title":"Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation","authors":"Molly K. Grun, Praveen Honhar, Yazhe Wang, Samantha Rossano, Minsoo Khang, Hee Won Suh, Krista Fowles, Harvey J. Kliman, Alessandra Cavaliere, Richard E. Carson, Bernadette Marquez-Nostra, W. Mark Saltzman","doi":"10.1002/btm2.10661","DOIUrl":"10.1002/btm2.10661","url":null,"abstract":"<p>Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with <sup>89</sup>Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non-human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long-lasting vaginal dosage forms.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 5","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rawan Al-Kharboosh, Alex Bechtle, Stephany Y. Tzeng, Jiaying Zheng, Sujan Kumar Mondal, David R. Wilson, Carlos Perez-Vega, Jordan J. Green, Alfredo Quiñones-Hinojosa
{"title":"Therapeutic potential and impact of nanoengineered patient-derived mesenchymal stem cells in a murine resection and recurrence model of human glioblastoma","authors":"Rawan Al-Kharboosh, Alex Bechtle, Stephany Y. Tzeng, Jiaying Zheng, Sujan Kumar Mondal, David R. Wilson, Carlos Perez-Vega, Jordan J. Green, Alfredo Quiñones-Hinojosa","doi":"10.1002/btm2.10675","DOIUrl":"10.1002/btm2.10675","url":null,"abstract":"<p>Confounding results of engineered mesenchymal stem cells (MSCs) used as cellular vehicles has plagued technologies whereby success or failure of novel approaches may be dismissed or inaccurately ascribed solely to the biotechnology platform rather than suitability of the human donor. Polymeric materials were screened for non-viral engineering of MSCs from multiple human donors to deliver bone morphogenic protein-4 (BMP4), a protein previously investigated in clinical trials for glioblastoma (GBM) to combat a subpopulation of highly invasive and tumorigenic clones. A “smart technology” that target the migratory and stem-like nature of GBM will require: (1) a cellular vehicle (MSC) which can scavenge and target residual cells left behind after surgical debulking and deliver; (2) anti-glioma cargo (BMP4). Multiple MSC donors are safely engineered, though varied in susceptibility to accept BMP4 due to intrinsic characteristics revealed by their molecular signatures. Efficiency is compared via secretion, downstream signaling, differentiation, and anti-proliferative properties across all donors. In a clinically relevant resection and recurrence model of patient-derived human GBM, we demonstrate that nanoengineered MSCs are not “donor agnostic” and efficacy is influenced by the inherent suitability of the MSC to the cargo. Therefore, donor profiles hold greater influence in determining downstream outcomes than the technical capabilities of the engineering technology.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibody drug conjugates in the clinic","authors":"Edidiong Udofa, Disha Sankholkar, Samir Mitragotri, Zongmin Zhao","doi":"10.1002/btm2.10677","DOIUrl":"10.1002/btm2.10677","url":null,"abstract":"<p>Antibody-drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell-killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)-approved products and discussing over 500 active clinical trials investigating newer ADCs. We also discuss some key challenges associated with the clinical translation of ADCs and highlight emerging strategies to overcome these hurdles. Our discussions will provide useful guidelines for the future development of safer and more effective ADCs for a broader range of indications.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A stretchable, electroconductive tissue adhesive for the treatment of neural injury","authors":"Jharana Dhal, Mahsa Ghovvati, Avijit Baidya, Ronak Afshari, Curtis L. Cetrulo Jr, Reza Abdi, Nasim Annabi","doi":"10.1002/btm2.10667","DOIUrl":"10.1002/btm2.10667","url":null,"abstract":"<p>Successful nerve repair using bioadhesive hydrogels demands minimizing tissue–material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation-mediated cell-signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue-like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom-designed chemically modified elastin-like polypeptides (ELPs) and a choline-based bioionic liquid (Bio-IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi-mode tissue–material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 5","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hemostats in the clinic","authors":"Maithili Joshi, Zongmin Zhao, Samir Mitragotri","doi":"10.1002/btm2.10673","DOIUrl":"10.1002/btm2.10673","url":null,"abstract":"<p>Given the prevalence of hematological conditions, surgeries, and trauma incidents, hemostats—therapeutics designed to control and arrest bleeding—are an important tool in patient care. The prophylactic and therapeutic use of hemostats markedly enhances survival rates and improves the overall quality of life of patients suffering from these conditions. Since their inception in the 1960s, hemostats have witnessed remarkable progress in terms of the active ingredients utilized, therapeutic outcomes, demonstrated efficacy, and the storage stability. In this review, we provide a comprehensive analysis of commercially available hemostats approved by the FDA, along with newer investigative hemostats currently in active clinical trials. We delve into the modality of active ingredients, route of administration, formulation type, and disease indications of these approved and investigative hemostats. Further, we analyze the trends observed in the hemostat actives for Hemophilia A and B, concluding with insights into the emerging patterns and noteworthy developments to watch for in this dynamic field.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew R. Stevens, Mohammed Hadis, Alice Phillips, Abhinav Thareja, Michael Milward, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed
{"title":"Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury","authors":"Andrew R. Stevens, Mohammed Hadis, Alice Phillips, Abhinav Thareja, Michael Milward, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed","doi":"10.1002/btm2.10674","DOIUrl":"10.1002/btm2.10674","url":null,"abstract":"<p>Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near-infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm<sup>2</sup>. 11 mW/cm<sup>2</sup> for 1 min per day (0.66 J/cm<sup>2</sup>) increased cell viability by 45% over 5 days (<i>p</i> <0.0001), increasing neurite outgrowth by 25% (<i>p</i> <0.01). A method for invasive application of PBM was developed using a diffusion-tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm<sup>2</sup> at spinal cord, 1 min per day (1.44 J/cm<sup>2</sup>) up to 7 days) increased activation of regeneration-associated protein at 3 days after SCI, increasing GAP43<sup>+</sup> axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (<i>p</i> <0.05). This corresponded to significant improvements at 6 weeks post-injury in functional locomotor and sensory function recovery (<i>p</i> <0.01), axonal regeneration (<i>p</i> <0.01), and reduced lesion size (<i>p</i> <0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas G. Biel, Talia Faison, Alicia M. Matthews, Uriel Ortega-Rodriguez, Vincent M. Falkowski, Edward Meek, Xin Bush, Matthew Flores, Sarah Johnson, Wells W. Wu, Mari Lehtimaki, Rong-Fong Shen, Cyrus Agarabi, V. Ashutosh Rao, Janice E. Chambers, Tongzhong Ju
{"title":"Model acetylcholinesterase-Fc fusion glycoprotein biotechnology system for the manufacture of an organophosphorus toxicant bioscavenging countermeasure","authors":"Thomas G. Biel, Talia Faison, Alicia M. Matthews, Uriel Ortega-Rodriguez, Vincent M. Falkowski, Edward Meek, Xin Bush, Matthew Flores, Sarah Johnson, Wells W. Wu, Mari Lehtimaki, Rong-Fong Shen, Cyrus Agarabi, V. Ashutosh Rao, Janice E. Chambers, Tongzhong Ju","doi":"10.1002/btm2.10666","DOIUrl":"10.1002/btm2.10666","url":null,"abstract":"<p>Organophosphate (OP) toxicants remain an active threat to public health and to warfighters in the military. Current countermeasures require near immediate administration following OP exposure and are reported to have controversial efficacies. Acetylcholinesterase (AChE) fused to the human immunoglobulin 1 (IgG1) Fc domain (AChE-Fc) is a potential bioscavenger for OP toxicants, but a reproducible AChE-Fc biomanufacturing strategy remains elusive. This report is the first to establish a comprehensive laboratory-scale bioprocessing strategy that can reproducibly produce AChE-Fc and AChE(W86A)-Fc which is a mutated AChE protein with reduced enzymatic activity. Characterization studies revealed that AChE-Fc and AChE(W86A)-Fc are <i>N</i>-glycosylated dimeric fusion glycoproteins but only AChE-Fc had the capability to bind to paraoxon (a model OP). This AChE-Fc fusion glycoprotein bioprocessing strategy can be leveraged during industrial biomanufacturing development, while the research-grade AChE-Fc proteins can be used to determine the potential clinical relevance of the countermeasure against OP toxicants.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 5","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Wu, Jiale Wang, Wenhui Fan, Qi Zhong, Rongyue Xue, Siyu Li, Zongming Song, Ye Tao
{"title":"Eye of the future: Unlocking the potential utilization of hydrogels in intraocular lenses","authors":"Hao Wu, Jiale Wang, Wenhui Fan, Qi Zhong, Rongyue Xue, Siyu Li, Zongming Song, Ye Tao","doi":"10.1002/btm2.10664","DOIUrl":"10.1002/btm2.10664","url":null,"abstract":"<p>Hydrogels are distinguished by their exceptional ability to absorb and retain large volumes of water within their complex three-dimensional polymer networks, which is advantageous for the development of intraocular lenses (IOLs). Their innate hydrophilicity offers an optimal substrate for the fabrication of IOLs that simulate the natural lens' accommodation, thereby reducing irritation and facilitating healing after surgery. The swelling and water retention characteristics of hydrogels contribute to their notable biocompatibility and versatile mechanical properties. However, the clinical application of hydrogels faces challenges, including managing potential adverse postimplantation effects. Rigorous research is essential to ascertain the safety and effectiveness of hydrogels. This review systematically examines the prospects and constraints of hydrogels as innovative materials for IOLs. Our comprehensive analysis examines their inherent properties, various classification strategies, cross-linking processes, and sensitivity to external stimuli. Additionally, we thoroughly evaluate their interactions with ocular tissues, underscoring the potential for hydrogels to be refined into seamless and biologically integrated visual aids. We also discuss the anticipated technological progress and clinical uses of hydrogels in IOL manufacturing. With ongoing technological advancements, the promise of hydrogels is poised to evolve from concept to clinical reality, marking a significant leap forward in ophthalmology characterized by improved patient comfort, enhanced functionality, and reliable safety.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 5","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tissue-engineered tracheal implants: Advancements, challenges, and clinical considerations","authors":"Shixiong Wei, Yiyuan Zhang, Feixiang Luo, Kexing Duan, Mingqian Li, Guoyue Lv","doi":"10.1002/btm2.10671","DOIUrl":"10.1002/btm2.10671","url":null,"abstract":"<p>Restoration of extensive tracheal damage remains a significant challenge in respiratory medicine, particularly in instances stemming from conditions like infection, congenital anomalies, or stenosis. The trachea, an essential element of the lower respiratory tract, constitutes a fibrocartilaginous tube spanning approximately 10–12 cm in length. It is characterized by 18 ± 2 tracheal cartilages distributed anterolaterally with the dynamic trachealis muscle located posteriorly. While tracheotomy is a common approach for patients with short-length defects, situations requiring replacement arise when the extent of lesion exceeds 1/2 of the length in adults (or 1/3 in children). Tissue engineering (TE) holds promise in developing biocompatible airway grafts for addressing challenges in tracheal regeneration. Despite the potential, the extensive clinical application of tissue-engineered tracheal substitutes encounters obstacles, including insufficient revascularization, inadequate re-epithelialization, suboptimal mechanical properties, and insufficient durability. These limitations have led to limited success in implementing tissue-engineered tracheal implants in clinical settings. This review provides a comprehensive exploration of historical attempts and lessons learned in the field of tracheal TE, contextualizing the clinical prerequisites and vital criteria for effective tracheal grafts. The manufacturing approaches employed in TE, along with the clinical application of both tissue-engineered and non-tissue-engineered approaches for tracheal reconstruction, are discussed in detail. By offering a holistic view on TE substitutes and their implications for the clinical management of long-segment tracheal lesions, this review aims to contribute to the understanding and advancement of strategies in this critical area of respiratory medicine.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10671","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}