Bioengineering & Translational Medicine最新文献

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.

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.

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 in vitro 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 in vitro 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 in vitro models.

Dhal J, Ghovvati M, Baidya A, et al. A stretchable, electroconductive tissue adhesive for the treatment of neural injury. Bioeng Transl Med. 2024;9(5):e10667. doi:10.1002/btm2.10667

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 ($��\mathrm{Sh}�$), 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 $��\mathrm{Sh}�<�1�$, 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.

Luo Y, Zheng S, Wang K, et al. Drug cross-linking electrospun fiber for effective infected wound healing. Bioeng Transl Med. 2023;8(6):e10540. doi:10.1002/btm2.10540

The corrected images are shown below. These errors will not affect the conclusion.

In Figure 5b, on day 4 (D4), we misused the image of TA Solution group for PVA Fiber group.

In Figure 9c, we misused the images of PVA Fiber group for TA/PVA Fiber group.

In Figure 10, for spleen images, we misused the image of TA Solution group for PVA Fiber group.

We apologize for these errors.

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.

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.

Volumetric muscle loss is the significant loss of skeletal muscle volume beyond the innate regenerative capacity, resulting in functional impairment. The current standard of care combines muscle autografting with physical therapy but is often insufficient to reach full recovery. Decellularized skeletal muscle (DSM) provides an interesting alternative to repair volumetric muscle loss. The native structure and composition of the extracellular matrix in these acellular implants provide a blueprint for muscle regeneration. Moreover, DSM can be combined with cells to facilitate the regeneration of the skeletal muscle defect. This systematic review provides a complete and thorough overview of the state-of-the-art applications and efficacy of DSM matrices in skeletal muscle repair in vivo, selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Technical information on the different methods to create DSM implants and the implantation studies is provided. Moreover, details on the evaluation of the structural and functional regeneration of the muscle defect after implantation of the DSM are described. Results reveal a large heterogeneity in the analysis of regeneration upon DSM implantation. This heterogeneity makes it difficult to fully assess the efficiency of DSM to regenerate skeletal muscle, hampering further translation of this technique. Therefore, we suggest a multi-level evaluation method to assess (i) muscle regeneration, (ii) vascularization, (iii) innervation of the regenerated muscle, and (iv) functional regeneration in a quantitative way.

Neuroblastoma is a highly aggressive pediatric cancer with a poor prognosis, particularly in high-risk (HR) cases characterized by MYCN amplification. The severe side effects associated with high-dose chemotherapy further complicate treatment. Despite significant advancements in drug screening, traditional platforms remain limited due to their requirement for large cell quantities and their low translational success from bench to clinic. These limitations hinder the application of personalized medicine screening for patients with neuroblastoma. To address these challenges, we developed a Bioinspired Nanodroplet Processing (BioNDP) platform. This innovative platform allows for the simultaneous screening of multiple drug combinations while reducing the required number of cells to just 100 and minimizing assay volumes to 200 nL per well. Using BioNDP, we screened chemotherapeutic combinations of cyclophosphamide, doxorubicin, and vincristine in both the SK-N-DZ neuroblastoma cell line and primary neuroblastoma cells derived from TH-MYCN transgenic mice. Our findings revealed a specific drug combination that exhibited significant synergistic cytotoxicity in neuroblastoma cells. This combination completely eradicated tumors and significantly improved survival rates in TH-MYCN mice, without notable side effects. This study highlights the potential of the BioNDP platform in bridging in vitro and in vivo results, offering a promising strategy for personalized medicine in the treatment of HR neuroblastoma, with reduced toxicity and enhanced therapeutic efficacy.