Bioengineering & Translational Medicine最新文献

{"title":"Highly efficient CRISPR/Cas9-mediated exon skipping for recessive dystrophic epidermolysis bullosa","authors":"Alex du Rand,&nbsp;John Hunt,&nbsp;Christopher Samson,&nbsp;Evert Loef,&nbsp;Chloe Malhi,&nbsp;Sarah Meidinger,&nbsp;Chun-Jen Jennifer Chen,&nbsp;Ashley Nutsford,&nbsp;John Taylor,&nbsp;Rod Dunbar,&nbsp;Diana Purvis,&nbsp;Vaughan Feisst,&nbsp;Hilary Sheppard","doi":"10.1002/btm2.10640","DOIUrl":"10.1002/btm2.10640","url":null,"abstract":"<p>Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient-specific skin equivalents. Precise gene editing using homology-directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress. Reframing strategies based on highly efficient non-homologous end joining (NHEJ) repair aimed at excising dispensable, mutation-harboring exons offer a promising alternative approach for restoring the <i>COL7A1</i> open reading frame. To this end, we employed an exon skipping strategy using dual single guide RNA (sgRNA)/Cas9 ribonucleoproteins (RNPs) targeted at three novel <i>COL7A1</i> exons (31, 68, and 109) containing pathogenic heterozygous mutations, and achieved exon deletion rates of up to 95%. Deletion of exon 31 in both primary human RDEB keratinocytes and fibroblasts resulted in the restoration of type VII collagen (C7), leading to increased cellular adhesion in vitro and accurate C7 deposition at the dermal-epidermal junction in a 3D skin model. Taken together, we extend the list of <i>COL7A1</i> exons amenable to therapeutic deletion. As an incidental finding, we find that long-read Nanopore sequencing detected large on-target structural variants comprised of deletions up to &gt;5 kb at a frequency of ~10%. Although this frequency may be acceptable given the high rates of intended editing outcomes, our data demonstrate that standard short-read sequencing may underestimate the full range of unexpected Cas9-mediated editing events.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489869","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":"In situ light-activated materials for skin wound healing and repair: A narrative review","authors":"Jordan R. Yaron,&nbsp;Mallikarjun Gosangi,&nbsp;Shubham Pallod,&nbsp;Kaushal Rege","doi":"10.1002/btm2.10637","DOIUrl":"10.1002/btm2.10637","url":null,"abstract":"<p>Dermal wounds are a major global health burden made worse by common comorbidities such as diabetes and infection. Appropriate wound closure relies on a highly coordinated series of cellular events, ultimately bridging tissue gaps and regenerating normal physiological structures. Wound dressings are an important component of wound care management, providing a barrier against external insults while preserving the active reparative processes underway within the wound bed. The development of wound dressings with biomaterial constituents has become an attractive design strategy due to the varied functions intrinsic in biological polymers, such as cell instructiveness, growth factor binding, antimicrobial properties, and tissue integration. Using photosensitive agents to generate crosslinked or photopolymerized dressings in situ provides an opportunity to develop dressings rapidly within the wound bed, facilitating robust adhesion to the wound bed for greater barrier protection and adaptation to irregular wound shapes. Despite the popularity of this fabrication approach, relatively few experimental wound dressings have undergone preclinical translation into animal models, limiting the overall integrity of assessing their potential as effective wound dressings. Here, we provide an up-to-date narrative review of reported photoinitiator- and wavelength-guided design strategies for in situ light activation of biomaterial dressings that have been evaluated in preclinical wound healing models.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480797","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":"Micro Trojan horses: Engineering extracellular vesicles crossing biological barriers for drug delivery","authors":"Bin Zeng,&nbsp;Ying Li,&nbsp;Jiang Xia,&nbsp;Yin Xiao,&nbsp;Nawaz Khan,&nbsp;Bin Jiang,&nbsp;Yujie Liang,&nbsp;Li Duan","doi":"10.1002/btm2.10623","DOIUrl":"10.1002/btm2.10623","url":null,"abstract":"<p>The biological barriers of the body, such as the blood–brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 μm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139431687","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":"Ultrasound molecular imaging for early detection of acute renal ischemia–reperfusion injury","authors":"Ling Ren,&nbsp;Yuzhuo Zhao,&nbsp;Tiantian Wang,&nbsp;Yan Tong,&nbsp;Ping Zhao,&nbsp;Fang Nie,&nbsp;Yukun Luo,&nbsp;Lianhua Zhu","doi":"10.1002/btm2.10638","DOIUrl":"10.1002/btm2.10638","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Microcirculatory perfusion disorder and inflammatory response are critical links in acute kidney injury (AKI). We aim to construct anti-vascular cell adhesion molecule-1(VCAM-1) targeted microbubbles (TM) to monitor renal microcirculatory perfusion and inflammatory response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TM carrying VCAM-1 polypeptide was constructed by biological coupling. The binding ability of TM to human umbilical vein endothelial cells (HUVECs) was detected. Bilateral renal ischemia–reperfusion injury (IRI) models of mice were established to evaluate microcirculatory perfusion and inflammatory response using TM. Thirty-six mice were randomly divided into six groups according to the different reperfusion time (0.5, 2, 6, 12, and 24 h) and sham-operated group (Sham group). The correlation of TM imaging with serum and histopathological biomarkers was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TM has advantages such as uniform distribution, regular shape, high stability, and good biosafety. TM could bind specifically to VCAM-1 molecule expressed by tumor necrosis factor-alpha (TNF-α)-treated HUVECs. In the renal IRI-AKI model, the area under the curve (AUC) of TM significantly decreased both in the renal cortical and medullary after 2 h of reperfusion compared with the Sham group (<i>p</i> &lt; 0.05). Normalized intensity difference (NID) of TM at different reperfusion time was all higher than that of blank microbubbles (BM) and the Sham group (<i>p</i> &lt; 0.05). Ultrasound molecular imaging of TM could detect AKI early before commonly used renal function markers, histopathological biomarkers, and BM imaging. AUC of TM was negatively correlated with serum creatinine (Scr), blood urea nitrogen (BUN), and Cystatin C (Cys-C) levels, and NID of TM was linearly correlated with VCAM-1, TNF-α, and interleukin-6 (IL-6) expression (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Ultrasound molecular imaging based on TM carrying VCAM-1 polypeptide can accurately evaluate the changes in renal microcirculatory perfusion and inflammatory response, which might be a promising modality for early diagnosis of AKI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110487","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":"Feasibility of engineered Bacillus subtilis for use as a microbiome-based topical drug delivery platform","authors":"Veronica A. Montgomery,&nbsp;Amy J. Wood-Yang,&nbsp;Mark P. Styczynski,&nbsp;Mark R. Prausnitz","doi":"10.1002/btm2.10645","DOIUrl":"10.1002/btm2.10645","url":null,"abstract":"<p>Non-adherence to medication is a major challenge in healthcare that results in worsened treatment outcomes for patients. Reducing the frequency of required administrations could improve adherence but is challenging for topical drug delivery due to the generally short residence time of topical formulations on the skin. In this study, we sought to determine the feasibility of developing a microbiome-based, long-acting, topical delivery platform using <i>Bacillus subtilis</i> for drug production and delivery on the skin, which was assessed using green fluorescent protein as a model heterologous protein for delivery. We developed a computational model of bacteria population dynamics on the skin and used its qualitative predictions to guide experimental design choices. Using an <i>ex vivo</i> pig skin model and a human skin tissue culture model, we saw persistence of delivered bacteria for multiple days and observed little evidence of cytotoxicity to human keratinocyte cells <i>in vitro</i>. Finally, using an in vivo mouse model, we found that the delivered bacteria persisted on the skin for at least 1 day during every-other-day application and did not appear to present safety concerns. Taken together, our results support the feasibility of using engineered <i>B. subtilis</i> for topical drug delivery.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076851","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":"An AI-assisted integrated, scalable, single-cell phenomic-transcriptomic platform to elucidate intratumor heterogeneity against immune response","authors":"Christopher P. Tostado,&nbsp;Lucas Xian Da Ong,&nbsp;Joel Jia Wei Heng,&nbsp;Carlo Miccolis,&nbsp;Shumei Chia,&nbsp;Justine Jia Wen Seow,&nbsp;Yi-Chin Toh,&nbsp;Ramanuj DasGupta","doi":"10.1002/btm2.10628","DOIUrl":"10.1002/btm2.10628","url":null,"abstract":"<p>We present a novel framework combining single-cell phenotypic data with single-cell transcriptomic analysis to identify factors underpinning heterogeneity in antitumor immune response. We developed a pairwise, tumor-immune discretized interaction assay between natural killer (NK-92MI) cells and patient-derived head and neck squamous cell carcinoma (HNSCC) cell lines on a microfluidic cell-trapping platform. Furthermore we generated a deep-learning computer vision algorithm that is capable of automating the acquisition and analysis of a large, live-cell imaging data set (&gt;1 million) of paired tumor-immune interactions spanning a time course of 24 h across multiple HNSCC lines (<i>n</i> = 10). Finally, we combined the response data measured by Kaplan–Meier survival analysis against NK-mediated killing with downstream single-cell transcriptomic analysis to interrogate molecular signatures associated with NK-effector response. As proof-of-concept for the proposed framework, we efficiently identified MHC class I-driven cytotoxic resistance as a key mechanism for immune evasion in nonresponders, while enhanced expression of cell adhesion molecules was found to be correlated with sensitivity against NK-mediated cytotoxicity. We conclude that this integrated, data-driven phenotypic approach holds tremendous promise in advancing the rapid identification of new mechanisms and therapeutic targets related to immune evasion and response.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389698","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":"Growth factors and growth factor gene therapies for treating chronic wounds","authors":"James A. Mullin,&nbsp;Erfan Rahmani,&nbsp;Kristi L. Kiick,&nbsp;Millicent O. Sullivan","doi":"10.1002/btm2.10642","DOIUrl":"10.1002/btm2.10642","url":null,"abstract":"<p>Chronic wounds are an unmet clinical need affecting millions of patients globally, and current standards of care fail to consistently promote complete wound closure and prevent recurrence. Disruptions in growth factor signaling, a hallmark of chronic wounds, have led researchers to pursue growth factor therapies as potential supplements to standards of care. Initial studies delivering growth factors in protein form showed promise, with a few formulations reaching clinical trials and one obtaining clinical approval. However, protein-form growth factors are limited by instability and off-target effects. Gene therapy offers an alternative approach to deliver growth factors to the chronic wound environment, but safety concerns surrounding gene therapy as well as efficacy challenges in the gene delivery process have prevented clinical translation. Current growth factor delivery and gene therapy approaches have primarily used single growth factor formulations, but recent efforts have aimed to develop multi-growth factor approaches that are better suited to address growth factor insufficiencies in the chronic wound environment, and these strategies have demonstrated improved efficacy in preclinical studies. This review provides an overview of chronic wound healing, emphasizing the need and potential for growth factor therapies. It includes a summary of current standards of care, recent advances in growth factor, cell-based, and gene therapy approaches, and future perspectives for multi-growth factor therapeutics.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051018","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":"Trafficking through the blood–brain barrier is directed by core and outer surface components of layer-by-layer nanoparticles","authors":"Nicholas G. Lamson,&nbsp;Andrew J. Pickering,&nbsp;Jeffrey Wyckoff,&nbsp;Priya Ganesh,&nbsp;Elizabeth A. Calle,&nbsp;Joelle P. Straehla,&nbsp;Paula T. Hammond","doi":"10.1002/btm2.10636","DOIUrl":"10.1002/btm2.10636","url":null,"abstract":"<p>Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood–brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice. We identify that hyaluronic acid surface chemistry increases transport across the BBB in vivo, and flow conditions are necessary to replicate this finding in vitro. Taken together, these findings highlight the importance of assay geometry, cell biology, and fluid flow in developing nanocarriers for delivery to the brain.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139061235","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":"Differential sensitivity to hypoxia enables shape-based classification of sickle cell disease and trait blood samples at point of care","authors":"Claudy D'Costa,&nbsp;Oshin Sharma,&nbsp;Riddha Manna,&nbsp;Minakshi Singh,&nbsp;Samrat Singh,&nbsp;Srushti Singh,&nbsp;Anish Mahto,&nbsp;Pratiksha Govil,&nbsp;Sampath Satti,&nbsp;Ninad Mehendale,&nbsp;Yazdi Italia,&nbsp;Debjani Paul","doi":"10.1002/btm2.10643","DOIUrl":"10.1002/btm2.10643","url":null,"abstract":"<p>Red blood cells (RBCs) become sickle-shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high-performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy-based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single-blinded proof-of-concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource-limited settings with the same accuracy as a gold standard test.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 4","pages":""},"PeriodicalIF":6.1,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051012","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":"Schwann cells acquire a repair phenotype after assembling into spheroids and show enhanced in vivo therapeutic potential for promoting peripheral nerve repair","authors":"Shih-Heng Chen,&nbsp;Hsin-Wen Wang,&nbsp;Pei-Ching Yang,&nbsp;Shih-Shien Chen,&nbsp;Chia-Hsin Ho,&nbsp;Pei-Ching Yang,&nbsp;Ying-Chi Kao,&nbsp;Shao-Wen Liu,&nbsp;Han Chiu,&nbsp;Yu-Jie Lin,&nbsp;Er-Yuan Chuang,&nbsp;Jen-Huang Huang,&nbsp;Huang-Kai Kao,&nbsp;Chieh-Cheng Huang","doi":"10.1002/btm2.10635","DOIUrl":"10.1002/btm2.10635","url":null,"abstract":"<p>The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051014","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}