Bioengineering & Translational Medicine最新文献

{"title":"Feasibility and pharmacokinetic evaluation of a needle‐free injector for delivering high concentration antibody formulations","authors":"Alexander Josowitz, Arjun Sree Manoj, Danielle Laiacona, Marc Pelletier, Diana Molano, Samuel Jennings, Cassie Ng, Charlotte Antoni, Grace Chan, Robert Mahoney, Sanket Patel, Ellen‐Marie Koehler‐Stec, Marc Retter, Joel Kantrowitz, Bindhu Rayaprolu, Eric Holowka, Amardeep Singh Bhalla, Mohammed Shameem","doi":"10.1002/btm2.70063","DOIUrl":"https://doi.org/10.1002/btm2.70063","url":null,"abstract":"The increased preference amongst health care providers and patients for subcutaneous (SC) administration of biologics has necessitated the development of higher concentration formulations to maintain doses similar to intravenous (IV) products. These formulations possess manufacturing and administration challenges; particularly high concentration monoclonal antibody (mAb) formulations push the limit of injectability. Furthermore, patient‐centric considerations, such as pain and fear of needles (trypanophobia), can lead to compliance deviations for long‐term treatments. This study presents a set of evaluations of a novel computer‐controlled, needle‐free injector (NFI) design that can deliver 2.0 mL of a high viscosity (50 cP) mAb formulation into the SC space. Critical attributes such as antibody purity, aggregation, color, turbidity, and charge heterogeneity were evaluated before and after ejection and demonstrated minimal change compared to ejection from a 27‐gauge needle and syringe (N&amp;S). Furthermore, the device functionality was evaluated in a novel ex vivo pig skin model, demonstrating the ability to accurately deposit a 2.0 mL dose at an appropriate depth in the SC tissue, though requiring 8% greater fill volume than an N&amp;S. An in vivo Yorkshire pig model was used to understand the pharmacokinetic (PK) profile of the NFI in comparison to a N&amp;S. Clearance (CL), the observed peak concentration in serum (<jats:italic>C</jats:italic><jats:sub>max</jats:sub>), the time until <jats:italic>C</jats:italic><jats:sub>max</jats:sub> (<jats:italic>T</jats:italic><jats:sub>max</jats:sub>), area under the concentration‐time curve extrapolated to infinity (AUC<jats:sub>inf</jats:sub>), and half‐life (<jats:italic>t</jats:italic><jats:sub>1/2</jats:sub>) were all within 1.2 fold and considered similar between the NFI and N&amp;S. A non‐significant difference in <jats:italic>T</jats:italic><jats:sub>max</jats:sub> was also observed. Bioavailability relative to IV administration was similar between the NFI (80.0%) and N&amp;S (79.5%) groups. No concerning clinical observations and injection site reactions were observed. Ultimately, the NFI represents an advancement in SC delivery of high concentration mAb formulations with patient‐centric design. This device could facilitate clinical and at‐home use while complementing efforts to bridge IV and SC formulations.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"28 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site‐specific noninvasive delivery of retrograde viral vectors to the brain","authors":"Manwal Harb, Shirin Nouraein, Jerzy O. Szablowski","doi":"10.1002/btm2.70062","DOIUrl":"https://doi.org/10.1002/btm2.70062","url":null,"abstract":"Neuronal activity underlies the brain function. Different behaviors, physiological processes, and disorders depend on which neurons are active at a given moment. Treating brain disorders without side effects will require exclusive control of disease‐relevant neurons. Traditionally, small molecule drugs could control a subset of neurons that express a molecularly specific receptor. Local noninvasive therapies such as delivery of neuromodulatory agents with focused ultrasound blood–brain barrier opening (FUS‐BBBO) also added spatial precision, allowing one to control specific brain regions without surgery. However, the final characteristic of neurons, which other neurons they connect to, remains underexplored as a therapeutic target. If targeting neurons based on their connectivity was possible noninvasively, it would open the doors to broadly deployable precise therapies that can target selected subgroups of neurons within a brain region. Such delivery could be achieved with retrograde‐tracing adeno‐associated viral vectors (AAVs). For noninvasive delivery with FUS‐BBBO, AAV9 has emerged as the most promising serotype. However, its retrograde‐tracing version, the AAV9.retro, has not been evaluated for FUS‐BBBO delivery. Here, we show that following such noninvasive delivery, AAV9.retro can safely transduce neuronal projections with comparable efficiency to a direct intracranial injection. Compared to AAV8, a naturally occurring vector with low retrograde transduction, AAV9.retro offers superior retrograde transduction and comparable transduction at the site of delivery. Overall, we show that AAV9.retro is a valuable FUS‐BBBO gene delivery vector, while also highlighting the surprising possibility of improved specificity of transduction of projections compared to invasive delivery.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"13 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced hydrogel therapeutics for intervertebral disc degeneration: Engineering structural–functional properties in natural and synthetic biomaterials","authors":"Tao Chen, Dading Lu, Siqiao Wang, Huiyi Yang, Wenyong Fan, Zhihui Xiao, Zhaojie Wang, Pooyan Makvandi, Rongrong Zhu, Liming Cheng","doi":"10.1002/btm2.70059","DOIUrl":"https://doi.org/10.1002/btm2.70059","url":null,"abstract":"Low back pain is a global health challenge, imposing substantial socioeconomic burdens. Intervertebral disc degeneration (IVDD) is a leading cause of low back pain and can lead to further spinal complications. Current treatments for IVDD are limited to conservative measures and surgery, lacking curative options. Advances in biomaterials science and regenerative medicine have introduced bioactive hydrogels as promising treatments for IVDD. This review summarizes the physiology of the intervertebral disc, the pathophysiology of IVDD, existing diagnostic methods, and current treatment strategies. Importantly, this review examines recent advances in hydrogel treatments for IVDD, emphasizing the biological and material properties of various hydrogels. It compares the advantages and limitations of natural and synthetic hydrogels, outlining the classification of hydrogel delivery substances. Lastly, it identifies current challenges and suggests future research directions to optimize the application of bioactive materials in IVDD treatment.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"15 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printed nerve guidance conduit for biologics‐free nerve regeneration and vascular integration","authors":"Jacob Schimelman, David B. Berry, Susie Johnson, Zhitian Ruskin Shi, Sophie Brown, Quyen T. Nguyen, Shaochen Chen","doi":"10.1002/btm2.70057","DOIUrl":"https://doi.org/10.1002/btm2.70057","url":null,"abstract":"There is a clinical need for an effective nerve guidance conduit to treat peripheral nerve injuries. Many studies have explored different materials and active cues to guide neural regeneration, with some success. However, none have demonstrated a comparable or better functional recovery than the clinical standard autograft. Autografts are often insufficient for reconstruction of an injury to long nerves such as the sciatic or brachial plexus. Synthetic nerve guidance conduits (NGCs) have been investigated for these injuries to guide axonal regeneration and lead to functional recovery. We have designed a biologics‐free hydrogel‐based multi‐channel conduit with defined microscale features to guide axonal outgrowth. To investigate extraneural vascular infiltration and its effects on functional recovery, we also designed a multi‐microchannel conduit with defined regularly spaced micropores, orthogonal to the axon guidance channels. Using our custom‐built Rapid Projection, Image‐guided, Dynamic (RaPID) bioprinting system, we were able to fabricate each hydrogel conduit within minutes from a milliliter‐volume prepolymer vat. With our state‐of‐the‐art printing platform, we have achieved NGCs with a consistent channel wall width of 10 μm. We implanted the NGCs for 17 weeks in a murine sciatic nerve transection injury model. We assessed the functional recovery by dynamic gait analysis throughout the recovery period and by compound muscle action potential (CMAP) electrophysiology before NGC harvesting. Both the non‐porous and micro‐porous conduit groups led to functional nerve regeneration on par with the autograft group. Further, both conduit groups resulted in restoration of bulk motor function to pre‐injury performance.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"142 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi‐modal screening for synergistic neuroprotection of mild extremely preterm brain injury","authors":"Zheyu Ruby Jin, Kylie A. Corry, Olivia C. Brandon, Matthew J. Magoon, Hawley Helmbrecht, Daniel H. Moralejo, Robell Bassett, Sarah E. Kolnik, Patrick M. Boyle, Sandra E. Juul, Elizabeth A. Nance, Thomas R. Wood","doi":"10.1002/btm2.70058","DOIUrl":"https://doi.org/10.1002/btm2.70058","url":null,"abstract":"Preterm brain injury affects both white and gray matter, including altered cortical development and gyrification, with associated neurodevelopmental sequelae such as cerebral palsy and learning deficits. The preterm brain also displays regionally heterogeneous responses to both injury and treatment, suggesting that drug combinations may be needed to provide global neuroprotection. We developed an extremely preterm‐equivalent organotypic whole hemisphere (OWH) slice culture mild injury model using the gyrencephalic ferret brain to probe treatment mechanisms of promising therapeutic agents and their combination. Regional and global responses to injury and treatment were assessed by cell death quantification, machine learning‐augmented morphological microglia assessments, and digital transcriptomics. Using two promising therapeutic agents, azithromycin (Az) and erythropoietin (Epo), we show minimal neuroprotection by either therapy alone, but evidence of synergistic neuroprotection by Az*Epo both globally and regionally. This effect of Az*Epo involved augmentation of transcriptomic responses to injury related to neurogenesis and neuroplasticity and downregulation of transcripts involved in cytokine production, inflammation, and cell death. With the increasing need to develop therapies for extremely preterm brain injury, the ferret OWH slice culture model provides a high‐throughput platform to examine combinations of therapeutics as part of a preclinical therapeutic pipeline.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"6061 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease”","authors":"","doi":"10.1002/btm2.70052","DOIUrl":"10.1002/btm2.70052","url":null,"abstract":"<p>Zhang B, Zhao Y, Guo K, et al. Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease. <i>Bioeng Transl Med</i>. 2023;8(3):e10459.</p><p>In the DAPI channel of figure 3g. The pictures above and below have been reversed. This is incorrect. The correct pictures should be reordered.</p><p>We apologize for this error.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763310","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":"Decellularized lymph node scaffolds accelerate restoration of lymphatic drainage in rat hind limb lymphedema","authors":"Yang Jian, Jian Zhou, Wenjie Pan, Jiayin Chen, Yanji Zhang, Yanqi Li, Xin Liu, Shune Xiao, Chenliang Deng, Zairong Wei","doi":"10.1002/btm2.70056","DOIUrl":"https://doi.org/10.1002/btm2.70056","url":null,"abstract":"BackgroundThere is a lack of effective lymphedema prevention methods. The objective of this study was to investigate the ability of decellularized lymph nodes (dLNs) transplantation to prevent hindlimb lymphedema.MethodsPorcine dLNs were prepared using 1% sodium dodecyl sulfate and 1% Triton X‐100, and the effectiveness of decellularization was assessed by histological assessment and DNA quantification. Lymph node (LN) fragments and dLNs were transplanted into mice, and samples were collected for evaluating biocompatibility at the fourth week postsurgery. Thirty‐six SD rats were separated into a control group (lymphatic dissection), a dLNs group (lymphatic dissection and dLNs transplant) and a sham group (inguinal skin circumferentially incised). Hindlimb circumference was monitored every 3 days. Indocyanine green lymphography was performed before and every week after surgery. Samples were collected for histological assessment at the second and fourth weeks.ResultsThe dLNs showed virtually complete absence of cellular material, maintenance of spatial structures, and good biocompatibility and induced immune cell infiltration. Compared with that of the control group, the average hindlimb circumference of the dLN group was significantly reduced on postoperative days (PODs) 8, 12, and 16, and that of the sham group was significantly reduced on PODs 4, 8, 12, 16, and 20. The sham group exhibited intact inguinal LNs and lymphatic drainage. Neonatal lymphatic vessels (LVs) were observed in the dLN group, and obvious dermal backflow was observed in the control group. Transplanted dLNs induced the infiltration of immune cells, which subsequently integrated into the preexisting lymphatic system. Compared with those in the control group or sham group, the number of LYVE‐1<jats:sup>+</jats:sup> LVs in the affected limb was greater in the dLN group.ConclusionThe dLNs scaffolds induced the infiltration of immune cells and promoted LVs regeneration, which integrated into the preexisting lymphatic system to accelerate the restoration of lymphatic drainage.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"29 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease modifying biomaterials for modulating mechanical allodynia in a preclinical model of rheumatoid arthritis","authors":"Maksim Dolmat, Julia Borges Paes Lemes, Wade T. Johnson, Elizabeth L. Wilkinson, Tony L. Yaksh, Nunzio Bottini, Nisarg J. Shah","doi":"10.1002/btm2.70054","DOIUrl":"https://doi.org/10.1002/btm2.70054","url":null,"abstract":"Pain is a key symptom associated with rheumatoid arthritis (RA) and can persist even in the context of overall disease control by standard‐of‐care disease modifying anti‐rheumatic drugs (DMARDs). Analgesic agents and corticosteroids are often used to supplement DMARDs for pain relief but lack disease modifying properties, and their sustained use carries adverse risks. In this work, we characterized the progression of pain sensitivity in the SKG mouse model of RA and evaluated the potential therapeutic interventions. Male and female SKG mice, after systemic mannan injection, developed a mechanical pain phenotype and joint swelling, with a strong inverse correlation between clinical arthritis scores and pain thresholds. To test potential interventions for pain alleviation, we evaluated all‐trans retinoic acid (ATRA)‐loaded poly(lactic‐co‐glycolic acid) microparticles (ATRA‐PLGA MP) administered via intra‐articular injection, which we have previously demonstrated to be disease‐modifying. The pain and inflammation patterns assessed by the von Frey test and clinical scoring showed ATRA‐PLGA MP monotherapy reduced inflammation and alleviated mechanical allodynia in arthritic SKG mice, an effect that was amplified by combination treatments with standard‐of‐care agents. In early‐stage arthritis, co‐administration with cytotoxic T‐lymphocyte‐associated protein (CTLA)‐4‐Ig, clinically known as abatacept, delayed disease progression and sustained the reduction of mechanical allodynia. In established arthritis, sequential treatment with the corticosteroid dexamethasone (Dex) reduced cumulative disease burden and reduced mechanical allodynia. These findings highlight the potential of combining ATRA‐PLGA MP with standard‐of‐care treatments as a potential strategy to enhance the efficacy and durability of disease modification and pain alleviation for arthritis management.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"722 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing cancer treatment: The multifaceted role of graphene oxide in modern oncology","authors":"Yutong Wu, Ting Zhu, Kou Wu, Zean Wang, Sizhe Jiao, Jiaxin Li, Weihong Guo, Xiaoli Feng","doi":"10.1002/btm2.70055","DOIUrl":"https://doi.org/10.1002/btm2.70055","url":null,"abstract":"The rising global incidence and mortality rates of cancer underscore the persistent reliance on chemotherapy as the primary treatment modality. Despite its widespread use, challenges such as chemotherapy resistance and the absence of tumor‐specific targeting have limited its efficacy, thereby necessitating the development of more effective therapeutic strategies in clinical practice. In this context, nanomaterials have opened up new avenues for cancer therapy. Among these, nanoparticles like graphene oxide (GO) exhibit significant potential due to their large specific surface area, high biocompatibility, abundance of oxygen‐containing functional groups, and exceptional biocompatibility. This review systematically summarizes the intrinsic antitumor properties of GO and emphasizes its role in enhancing the delivery and therapeutic efficacy of chemotherapeutic agents, gene drugs, and natural compounds through multiple mechanisms. It further highlights GO's potential in synergistic chemotherapy, targeted therapy, tumor monitoring platforms, and cancer vaccine development, while also discussing the manufacturing challenges that limit clinical translation, aiming to provide theoretical guidance and innovative strategies for its future application in oncology.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"137 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fiber‐Electrospun Hydrogel Therapy for DNP: A synergistic electrospun‐hydrogel composite for alleviating diabetic neuropathic pain via MMP9 regulation and sodium channel inhibition","authors":"Wen Chen, Ji Chen, Yingqing Lu, Yangyuxi Chen, Xinxin Liu, Fengrui Yang","doi":"10.1002/btm2.70050","DOIUrl":"https://doi.org/10.1002/btm2.70050","url":null,"abstract":"Diabetic neuropathic pain (DNP) remains a significant challenge in diabetes care, and effective therapeutic strategies are urgently needed. This study introduces an innovative electrospinning‐hydrogel composite, Fiber‐SIN/Gel‐LidC, designed for the controlled and synergistic release of Sinomenine (SIN) and Lidocaine (Lid). Bioinformatics and network pharmacology analyses identified MMP9 as a key player in DNP alleviation. The composite, composed of SIN‐loaded fibers and Lid microcrystals, ensures sustained drug release over 7 days, demonstrating excellent biocompatibility. In vivo experiments on diabetic rats revealed significant improvements in thermal and mechanical pain thresholds, along with a reduction in sciatic nerve excitability. Additionally, the composite significantly attenuated neuroinflammation, neuronal apoptosis, and morphological damage. Mechanistic studies highlighted the neuroprotective effects of Fiber‐SIN/Gel‐LidC, particularly through the regulation of MMP9 and inhibition of sodium channels. These findings suggest that Fiber‐SIN/Gel‐LidC holds great potential as an innovative biomaterial‐based approach for managing DNP, offering promising therapeutic prospects for diabetic neuropathy.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"68 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}