Bioengineering & Translational Medicine最新文献

{"title":"Optimizing design parameters of 3D-printed poly-4-hydroxybutyrate nipple scaffolds for nipple reconstruction","authors":"Xue Dong,&nbsp;Sophia Salingaros,&nbsp;Timothy Butler,&nbsp;Skander Limem,&nbsp;Jason A. Spector","doi":"10.1002/btm2.70010","DOIUrl":"10.1002/btm2.70010","url":null,"abstract":"<p>Nipple reconstruction in patients who undergo total mastectomy or nipple-sparing mastectomy is currently limited by a consistent and significant loss of nipple projection over time, which can negatively affect patient satisfaction and quality of life. To address this issue, we have previously shown that 3D-printed poly-4-hydroxybutyrate (P4HB) nipple-shaped scaffolds promote long-term maintenance of nipple projection in a rat model. Herein, we further optimize the 3D printing parameters (filament diameter and infill density) of absorbable P4HB latticework scaffolds as well as scaffolds fabricated from rolled P4HB knitted mesh to facilitate tissue formation with similar biomechanical properties of the native nipple, while maintaining long-term shape and projection. Over 12 months of in vivo implantation in a dorsal, bilateral CV-flap rat model of nipple reconstruction, 3D-printed P4HB latticework and knitted mesh scaffolded groups demonstrated significantly greater maintenance in projection (80–100% of initial value) when compared to the Cook Biodesign® Nipple Cylinder (~40% of initial projection), resulting from the infiltration of healthy fibrovascular adipose tissue, which demonstrated biomechanical qualities that approached those of the native human nipple. Overall, our results demonstrate that using a 3D-printed P4HB latticework and rolled P4HB knitted mesh scaffolds significantly improved long-term results in our animal model of nipple reconstruction and hold promise for improving nipple reconstruction outcomes in future clinical practice.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797859","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":"Spatial-hindrance-based pro-Adalimumab prevents anti-idiotypic antibody interference in pharmacokinetic and therapeutic efficacy","authors":"Bo-Cheng Huang,&nbsp;Yu-Tung Chen,&nbsp;Yun-Chi Lu,&nbsp;Kai-Wen Ho,&nbsp;Shih-Ting Hong,&nbsp;Tzu-Yi Liao,&nbsp;I-Hsuan Wu,&nbsp;En-Shuo Liu,&nbsp;Jun-Min Liao,&nbsp;Fang-Ming Chen,&nbsp;Chia-Ching Li,&nbsp;Chih-Hung Chuang,&nbsp;Chiao-Yun Chen,&nbsp;Tian-Lu Cheng","doi":"10.1002/btm2.70015","DOIUrl":"10.1002/btm2.70015","url":null,"abstract":"<p>Adalimumab (Humira) represents a major advance in rheumatoid arthritis (RA) therapy. However, with long-term administration of Adalimumab, anti-idiotypic antibody (anti-Id Ab) accelerates the Adalimumab clearance rate and reduces the therapeutic effect. To avoid the interference of anti-Id Ab, we used an autologous hinge region as a spatial-hindrance-based Ab lock and connected it to the N-terminal of the light chain and heavy chain via substrate peptides (MMP-2/9) to cover the CDR binding site of Adalimumab to generate pro-Adalimumab. The Ab lock masks the complementarity-determining regions (CDRs) of Adalimumab, thus avoiding interference from anti-Id Ab. Pro-Adalimumab demonstrated a 241.6 times weaker binding ability to TNFɑ than Adalimumab. In addition, pro-Adalimumab showed a 46.6-fold greater blocking of anti-Adalimumab Id Ab in comparison to Adalimumab prior to activation. Similar results were observed with other clinical antibodies, such as pro-Infliximab (anti-TNFɑ Ab) and pro-Nivolumab (anti-PD-1). Furthermore, pro-Adalimumab maintained consistent pharmacokinetics regardless of the presence of anti-Adalimumab Id antibodies, while Adalimumab showed a 49% clearance increase, resulting in a near complete loss of function. Additionally, pro-Adalimumab was able to avoid neutralization and efficiently reduce RA progression in the presence of anti-Adalimumab Id Ab in vivo. In summary, we developed a pro-Adalimumab that avoids interference from anti-Id Abs, thereby addressing the biggest issue limiting clinical efficacy. The findings enclosed herein may have potentially broad application in antibody therapies.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782390","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":"Machine learning-based SERS serum detection platform for high-sensitive and high-throughput diagnosis of colorectal precancerous lesions","authors":"Qunshan Zhu,&nbsp;Gaoyang Chen,&nbsp;Lei Fu,&nbsp;Dawei Cao,&nbsp;Zhenguang Wang,&nbsp;Yan Yang,&nbsp;Wei Wei","doi":"10.1002/btm2.70019","DOIUrl":"10.1002/btm2.70019","url":null,"abstract":"<p>Colorectal precancerous lesions (CRP) are early signs of cancer development, and early detection helps prevent progression to colorectal cancer (CRC), reducing incidence and mortality rates. This study developed a serum detection platform integrating surface-enhanced Raman scattering (SERS) with machine learning (ML) for early detection of CRP. Specifically, a microarray chip with Au/SnO₂ nanorope arrays (Au/SnO₂ NRAs) substrate was designed for SERS spectral measurement of serum. The Principal Component Analysis (PCA)-Optimal Class Discrimination and Compactness Optimization (OCDCO) model was proposed to identify CRP spectra. The results demonstrated that the microarray chip exhibited superior portability, SERS activity, stability, and uniformity. Through PCA-OCDCO, the serum samples from healthy controls, CRP patients, and CRC patients were effectively classified, and several key spectral features for distinguishing different groups were identified. The established PCA-OCDCO model achieved outstanding performance, with an accuracy of 97%, a sensitivity of 95%, a specificity of 97%, and an AUC of 0.96. This study suggests that the platform, integrating SERS with the PCA-OCDCO model, holds potential for the early detection of CRP, providing an approach for CRP prevention and clinical diagnostics.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736612","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":"Efficacy and safety assessment of homotopical transplantation of iPSCs-derived midbrain organoids into the substantia nigra of Parkinsonian rats","authors":"Xin Zheng,&nbsp;Jianwei Chen,&nbsp;Zhengzheng Huang,&nbsp;Youcheng Zhang,&nbsp;Liping Zhou","doi":"10.1002/btm2.70014","DOIUrl":"10.1002/btm2.70014","url":null,"abstract":"<p>Current ectopic implantation has shown limited efficacy in promoting reinnervation of the nigrostriatal pathway, which is critically affected in Parkinson's disease (PD). Homotopic transplantation, on the other hand, may facilitate physiological cell rewiring of the basal ganglia, potentially improving PD symptoms. This study aimed to evaluate the efficacy and safety of homotopically engrafting human induced pluripotent stem cells (hiPSCs)-derived midbrain organoids into the substantia nigra of PD rats. A rat model of PD was induced using 6-hydroxydopamine (6-OHDA) and homotopically transplanted into the lesioned SN with hiPSC-derived hMOs. The engrafted hMOs survived and continually mature in host brains, and were mainly differentiated into dopaminergic lineage neurons, part of which presented TH⁺ fibers. Behavioral evaluation demonstrated that transplantation of hMOs gradually reverse the motor disorder caused by 6-OHDA lesioning by 22% at week 5 and 35% by week 10 post-transplantation, respectively. No tumor formation or migration was detected in either subcutaneous space or vital organs following 10 weeks implantation. These findings support the efficacy and safety of homotopical hMOs transplantation, offering a promising cell-based strategy for treating Parkinson's disease.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736604","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":"Key parameters for designing robust 2D and 3D spheroid models for in vitro atherosclerosis research","authors":"Ibukunoluwa Naiyeju,&nbsp;Stephanie Lehoux,&nbsp;Maryam Tabrizian","doi":"10.1002/btm2.10736","DOIUrl":"10.1002/btm2.10736","url":null,"abstract":"<p>Atherosclerosis is a chronic, systemic, inflammatory disease associated with the build-up of fatty deposits (“plaques”) in the arteries. A major global health burden, severe atherosclerosis progresses to ischemic heart disease, an underlying condition which can exacerbate the occurrence of fatal events such as heart attack and stroke. Over the past two decades, the use of <i>in vitro</i> models to study atherosclerotic phenomena has increased, with the goal of complementing clinical research for drug and therapy development. In particular, 2D co-culture models, and in the last decade, 3D spheroid models have been developed to improve our understanding of the atherosclerotic disease mechanism. However, the existing literature lacks information on the relevant parameters which should be considered prior and during the design of these models to promote model robustness and enhance their biomimetic capacities. This review provides an overview of such key parameters, as well as future perspectives on how existing limitations in the field of cell-based <i>in vitro</i> model design can be improved. It is expected that by carefully considering these parameters, researchers will be better equipped with the required knowledge to develop biomedically and clinically relevant <i>in vitro</i> models.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677641","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":"Correction to “A stretchable, electroconductive tissue adhesive for the treatment of neural injury”","authors":"","doi":"10.1002/btm2.10759","DOIUrl":"10.1002/btm2.10759","url":null,"abstract":"<p>Dhal J, Ghovvati M, Baidya A, et al. A stretchable, electroconductive tissue adhesive for the treatment of neural injury. <i>Bioeng Transl Med</i>. 2024;9(5):e10667. doi:10.1002/btm2.10667</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661299","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":"Transport physics-informed reinforcement learning agents deployed in standalone infusion pumps for managing multidrug delivery in critical care","authors":"V. Chandran Suja,&nbsp;A. L. H. S. Detry,&nbsp;N. M. Sims,&nbsp;D. E. Arney,&nbsp;S. Mitragotri,&nbsp;R. A. Peterfreund","doi":"10.1002/btm2.70013","DOIUrl":"10.1002/btm2.70013","url":null,"abstract":"<p>Managing delivery of complex multidrug infusions in anesthesia and critical care presents a significant clinical challenge. Current practices relying on manual control of infusion pumps often result in unpredictable drug delivery profiles and dosing errors—key issues highlighted by the United States Food and Drug Administration (FDA). To address these issues, we introduce the SMART (synchronized-pump management algorithms for reliable therapies) framework, a novel approach that leverages low Reynolds number drug transport physics and machine learning to accurately manage multidrug infusions in real-time. SMART is activated based on the Shafer number (<span></span><math>\u0000 <mrow>\u0000 <mi>Sh</mi>\u0000 </mrow></math>), a novel non-dimensional number that quantifies the relative magnitude of a drug's therapeutic action timescale to its transport timescale within infusion manifolds. SMART is useful when <span></span><math>\u0000 <mrow>\u0000 <mi>Sh</mi>\u0000 <mo>&lt;</mo>\u0000 <mn>1</mn>\u0000 </mrow></math>, where drug transport becomes the rate limiting step in achieving the desired therapeutic effects. When activated, SMART monitors multidrug concentrations within infusion manifolds and leverages this information to perform end-to-end management of drug delivery using an ensemble of deterministic and deep reinforcement learning (RL) decision networks. Notably, SMART RL networks employ differentially sampled split buffer architecture that accelerates learning and improves performance by seamlessly combining deterministic predictions with RL experience during training. SMART deployed in standalone infusion pumps under simulated clinical conditions outperformed state-of-the-art manual control protocols. This framework has the potential to revolutionize critical care by enhancing accuracy of medication delivery and reducing cognitive workloads. Beyond critical care, the ability to accurately manage multi-liquid delivery via complex manifolds will have important bearings for manufacturing and process control.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653389","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":"Correction to “Drug cross-linking electrospun fiber for effective infected wound healing”","authors":"","doi":"10.1002/btm2.10758","DOIUrl":"10.1002/btm2.10758","url":null,"abstract":"<p>Luo Y, Zheng S, Wang K, et al. Drug cross-linking electrospun fiber for effective infected wound healing. <i>Bioeng Transl Med</i>. 2023;8(6):e10540. doi:10.1002/btm2.10540</p><p>The corrected images are shown below. These errors will not affect the conclusion.</p><p>In Figure 5b, on day 4 (D4), we misused the image of TA Solution group for PVA Fiber group.</p><p>In Figure 9c, we misused the images of PVA Fiber group for TA/PVA Fiber group.</p><p>In Figure 10, for spleen images, we misused the image of TA Solution group for PVA Fiber group.</p><p>We apologize for these errors.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641041","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":"Paquinimod-hydrogel hybrid microneedle array patch alleviates hypertrophic scar via inhibiting M1 polarization","authors":"Zihui Zhang,&nbsp;Peng Wang,&nbsp;Hengdeng Liu,&nbsp;Hanwen Wang,&nbsp;Miao Zhen,&nbsp;Xuefeng He,&nbsp;Suyue Gao,&nbsp;Juntao Xie,&nbsp;Julin Xie","doi":"10.1002/btm2.70016","DOIUrl":"10.1002/btm2.70016","url":null,"abstract":"<p>Hypertrophic scar (HS) is one of the most common complications of skin injuries, with a lack of effective therapeutic approaches to date. Most current research has focused on the dysfunction of hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs), neglecting the crucial role of the inflammatory microenvironment that causes them to be abnormal. In this study, we first discovered and validated that the S100A8/9 specific inhibitor Paquinimod could inhibit macrophage polarization toward M1, and further suppress the proliferation, migration, collagen formation, and angiogenesis of HSFBs and HDVECs in vitro. This mechanism has also been validated in a rat model of HS. Then, we developed a good biocompatibility and penetrability Paquinimod-Hydrogel Hybrid Microneedle Array Patch (PHMAP) for HS treatment. With the advantages of excellent penetrability, surface sealing, sustained release, and precise uniform distribution, PHMAP exhibited superior therapeutic efficacy over intravenous and intradermal injections. These results suggest that PHMAP can be a promising and advanced solution for HS prevention and therapies.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631323","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":"Engineered microvascular basement membrane mimetic for real-time neutrophil tracking in the microvascular wall","authors":"Laura C. Morales,&nbsp;Catherine D. Kim,&nbsp;Yangang Pan,&nbsp;Simon Scheuring,&nbsp;Anjelica L. Gonzalez","doi":"10.1002/btm2.70008","DOIUrl":"10.1002/btm2.70008","url":null,"abstract":"<p>The microvascular basement membrane (mvBM) is crucial in maintaining vascular integrity and function and, therefore, key to the health of major organs. However, the complex nature and the intricate interplay of biochemical and biomechanical factors that regulate the mvBM functional dynamics make it difficult to study. Here, we present a novel and highly tunable in vitro model of the human mvBM, enabling a bottom-up approach to assemble a composite model of the microvascular wall and explore microvascular dynamics and interactions with circulating neutrophils in real time. An electrospun polyethylene glycol (PEG)-based fibrillar network mimics the mvBM with adjustable nanofiber diameter, orientation, and density. The fidelity of the model to the human mvBM's topography and mechanics was verified through second harmonic generation imaging and atomic force microscopy. PEG was functionalized with bioactive moieties to enable endothelial cell (EC) and pericyte (PC) attachment, through which neutrophil interactions with the microvascular wall model were observed. The model, coupled with 4D microscopy, revealed nuanced and dynamic neutrophil behavior when interacting with the microvascular wall, demonstrating its utility in characterizing cell–cell interactions. As such, the model can be employed in the exploration of inflammatory and microvascular-related diseases. Therefore, this innovative approach represents a significant advancement in vascular biology research, holding profound implications for understanding mvBM dynamics in both health and disease.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607891","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}