Adam Weisel, Rachael Cohen, Jason A. Spector, Yulia Sapir-Lekhovitser
{"title":"Accelerated vascularization of a novel collagen hydrogel dermal template","authors":"Adam Weisel, Rachael Cohen, Jason A. Spector, Yulia Sapir-Lekhovitser","doi":"10.1002/term.3356","DOIUrl":"https://doi.org/10.1002/term.3356","url":null,"abstract":"<p>Full thickness skin loss is a debilitating problem, most commonly reconstructed using split thickness skin grafts (STSG), which do not reconstitute normal skin thickness and often result in suboptimal functional and esthetic outcomes that diminish a patient's quality of life. To address the minimal dermis present in most STSG, engineered dermal templates were developed that can induce tissue ingrowth and the formation of neodermal tissue. However, clinically available dermal templates have many shortcomings including a relatively slow rate and degree of neovascularization (∼2–4 weeks), resulting in multiple dressing changes, prolonged immobilization, and susceptibility to infection. Presented herein is a novel composite hydrogel scaffold that optimizes a unique scaffold microarchitecture with native hydrogel properties and mechanical cues ideal for promoting neovascularization, tissue regeneration, and wound healing. <i>In vitro</i> analysis demonstrated the unique combination of improved mechanical attributes with native hydrogel properties that promotes cell invasion and remodeling within the scaffold. In a novel 2-stage rat model of full thickness skin loss that closely mimics clinical practice, the composite hydrogel induced rapid cell infiltration and neovascularization, creating a healthy neodermis after only 1 week onto which a skin graft could be placed. The scaffold also elicited a gradual and favorable immune response, resulting in more efficient integration into the host. We have developed a dermal scaffold that utilizes simple but unique collagen hydrogel architectural cues that rapidly induces the formation of stable, functional neodermal tissue, which holds tremendous promise for the treatment of full thickness skin loss.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1173-1183"},"PeriodicalIF":3.3,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5810267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ipek Karacan, Besim Ben-Nissan, Jerran Santos, Stanley Yiu, Peta Bradbury, Stella M. Valenzuela, Joshua Chou
{"title":"In vitro testing and efficacy of poly-lactic acid coating incorporating antibiotic loaded coralline bioceramic on Ti6Al4V implant against Staphylococcus aureus","authors":"Ipek Karacan, Besim Ben-Nissan, Jerran Santos, Stanley Yiu, Peta Bradbury, Stella M. Valenzuela, Joshua Chou","doi":"10.1002/term.3353","DOIUrl":"https://doi.org/10.1002/term.3353","url":null,"abstract":"<p>Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria <i>Staphylococcus aureus</i>, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose-dependent negative biological effect on human cells. Our aim was to improve current treatments via a localized and controlled antibiotic delivery-based implant coating system to deliver the antibiotic, gentamicin (Gm). The coating contains coral skeleton derived hydroxyapatite powders (HAp) that act as antibiotic carrier particles and have a biodegradable poly-lactic acid (PLA) thin film matrix. The system is designed to prevent implant related infections while avoiding the deleterious effects of high concentration antibiotics in implants on local cells including primary human adipose derived stem cells (ADSCs). Testing undertaken in this study measured the rate of <i>S</i>. <i>aureus</i> biofilm formation and determined the growth rate and proliferation of ADSCs. After 24 h, <i>S</i>. <i>aureus</i> biofilm formation and the percentage of live cells found on the surfaces of all 5%–30% (w/w) PLA-Gm-(HAp-Gm) coated Ti6Al4V implants was lower than the control samples. Furthermore, Ti6Al4V implants coated with up to 10% (w/w) PLA-Gm-(HAp-Gm) did not have noticeable Gm related adverse effect on ADSCs, as assessed by morphological and surface attachment analyses. These results support the use and application of the antibacterial PLA-Gm-(HAp-Gm) thin film coating design for implants, as an antibiotic release control mechanism to prevent implant-related infections.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1149-1162"},"PeriodicalIF":3.3,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6123225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A. Kowalski, Lorenzo M. Fernandes, Kyle E. Hammond, Sameh Labib, Hicham Drissi, Jay M. Patel
{"title":"Cartilage-penetrating hyaluronic acid hydrogel preserves tissue content and reduces chondrocyte catabolism","authors":"Michael A. Kowalski, Lorenzo M. Fernandes, Kyle E. Hammond, Sameh Labib, Hicham Drissi, Jay M. Patel","doi":"10.1002/term.3352","DOIUrl":"https://doi.org/10.1002/term.3352","url":null,"abstract":"<p>Articular cartilage injuries have a limited healing capacity and, due to inflammatory and catabolic activities, often experience progressive degeneration towards osteoarthritis. Current repair techniques generally provide short-term symptomatic relief; however, the regeneration of hyaline cartilage remains elusive, leaving both the repair tissue and surrounding healthy tissue susceptible to long-term wear. Therefore, methods to preserve cartilage following injury, especially from matrix loss and catabolism, are needed to delay, or even prevent, the deteriorative process. The goal of this study was to develop and evaluate a cartilage-penetrating hyaluronic-acid (HA) hydrogel to improve damaged cartilage biomechanics and prevent tissue degeneration. At time zero, the HA-based hydrogel provided a 46.5% increase in compressive modulus and a decrease in permeability after simulated degeneration of explants (collagenase application). Next, in a degenerative culture model (interleukin-1β [IL-1β] for 2 weeks), hydrogel application prior to or midway through the culture mitigated detrimental changes to compressive modulus and permeability observed in non-treated explants. Furthermore, localized loss of proteoglycan was observed in degenerative culture conditions alone (non-treated), but hydrogel administration significantly improved the retention of matrix elements. Finally, NITEGE staining and gene expression analysis showed the ability of the HA gel to decrease chondrocyte catabolic activity. These results highlight the importance of reinforcing damaged cartilage with a biomaterial system to both preserve tissue content and reduce catabolism associated with injury and inflammation.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1138-1148"},"PeriodicalIF":3.3,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5900916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Issue Information","authors":"","doi":"10.1111/pai.13596","DOIUrl":"https://doi.org/10.1111/pai.13596","url":null,"abstract":"No abstract is available for this article.","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46589829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In-depth analysis of the relationship between bovine intestinal organoids and enteroids based on morphology and transcriptome","authors":"Juntao Zhang, Juanjuan Li, Penghui Yan, Laizeng He, Xuemei Zhang, Xiaolong Wang, Yake Shi, Lixin Deng, ZhiPing Zhang, Baoyu Zhao","doi":"10.1002/term.3351","DOIUrl":"https://doi.org/10.1002/term.3351","url":null,"abstract":"<p>Intestinal organoids and enteroids as excellent models are miniaturized and simplified for studying intestinal physiological and pathological functions, drug screening, and regenerative medicine. Recently, the application demands for organoids and enteroids in organ development and nutrition metabolism, immune and cancer research increased. But there are few comparative studies on both of them, especially in immunity and metabolism, which is also conducive to further clarifying the role of crypt stem cells and stromal cells. In our study, “natural” organoids were obtained by tissue culture from fetal bovine jejunum and enteroids were successfully isolated and cultured from organoids without supplementing exogenous factors and Matrigel. These mini-guts displayed similar features to the intestine through immunohistochemistry and transmission electron microscopy. Organoid and enteroid were systematically compared based on the transcriptome. And some of the results were verified by qRT-PCR. Our results showed KDGs (Key driver genes) (e.g., SLC13A1, HOXA7, HOXA6, HOXA5, and HOXD4) of organoids enriched in signaling pathways related to organ development and morphology and metabolism. KDGs (e.g., IL-6, PTGS2, CDH1, JUN, and EGFR) of enteroid were involved in cancer, MAPK, and immune-related signaling pathways. To the Wnt signaling pathway, highly expressed genes in organoids, including RSPO2, NOTUM, WNT6, and RSPO3, supported the homeostasis of crypt stem cells. Enteroids highly expressed CTNNB1 and WNTs. In addition, we found that organoids and enteroids carried out different functions in immunity and metabolism due to different cell compositions. Therefore, it suggested organoid is more compatible and comprehensive, and enteroid is qualified for the research of immunity and cancer.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"1032-1046"},"PeriodicalIF":3.3,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5752752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert E. Marx, Paul Amailuk, Neel Patel, Andre Ledoux, Dani Stanbouly
{"title":"FlexMetric bone marrow aspirator yields laboratory and clinically improved results from mesenchymal stem and progenitor cells without centrifugation","authors":"Robert E. Marx, Paul Amailuk, Neel Patel, Andre Ledoux, Dani Stanbouly","doi":"10.1002/term.3348","DOIUrl":"https://doi.org/10.1002/term.3348","url":null,"abstract":"<p>Several devices used to harvest stem/progenitor cells from bone marrow are available to clinicians. This study compared three devices measuring stem cell yields and correlating those yields to bone regeneration. A flexible forward aspirating system Marrow Marxman (MM), a straight needle aspirating on withdrawal system Marrow Cellutions (MC), and a straight needle aspirating on withdrawal and centrifuging the aspirate (BMAC) were compared in a side-to-side patient comparison, as well as tissue engineered bone grafts. The FlexMetric system (MM) produced greater CFU-f values compared to the straight needle (MC) Δ = 1083/ml, <i>p</i> < 0.001 and 1225/ml, <i>p</i> < 0.001 than the BMAC system. This increased stem/progenitor cell yield also translated into a greater radiographic bone density at 6 months Δ = 88.3 Hu, <i>p</i> ≤ 0.001 versus MC and Δ = 116.7, <i>p</i> < 0.001 versus BMAC at 6 months and Δ = 72.2, <i>p</i> < 0.001 and Δ = 93.3, <i>p</i> < 0.001 at 9 months respectively. The increased stem/progenitor cell yield of the MM system clinically translated into greater bone regeneration as measured by bone volume <i>p</i> < 0.014 and <i>p</i> < 0.001 respectively, trabecular thickness <i>p</i> < 0.007 and <i>p</i> < 0.002 respectively, and trabecular separation <i>p</i> = 0.011 and <i>p</i> < 0.001. A flexible bone marrow aspirator produces higher yields of stem/progenitor cells. Higher yields of stem/progenitor cells translate into greater bone regeneration in tissue engineering. Flexmetric technology produces better bone regeneration due to a forward aspiration concept reducing dilution from peripheral blood and its ability to target lining cells along the inner cortex. Centrifugation systems are not required in tissue engineering procedures involving stem/progenitor cells due to nonviability or functional loss from g-forces.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"1047-1057"},"PeriodicalIF":3.3,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5887751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Laura Nelson, GianLuca Fontana, Elizabeth Miclau, Mallory Rongstad, William Murphy, Johnny Huard, Nicole Ehrhart, Chelsea Bahney
{"title":"Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration","authors":"Anna Laura Nelson, GianLuca Fontana, Elizabeth Miclau, Mallory Rongstad, William Murphy, Johnny Huard, Nicole Ehrhart, Chelsea Bahney","doi":"10.1002/term.3349","DOIUrl":"https://doi.org/10.1002/term.3349","url":null,"abstract":"<p>Activation of the canonical Wingless-related integration site (Wnt) pathway has been shown to increase bone formation and therefore has therapeutic potential for use in orthopedic conditions. However, attempts at developing an effective strategy to achieve Wnt activation has been met with several challenges. The inherent hydrophobicity of Wnt ligands makes isolating and purifying the protein difficult. To circumvent these challenges, many have sought to target extracellular inhibitors of the Wnt pathway, such as Wnt signaling pathway inhibitors Sclerostin and Dickkopf-1, or to use small molecules, ions and proteins to increase target Wnt genes. Here, we review systemic and localized bioactive approaches to enhance bone formation or improve bone repair through antibody-based therapeutics, synthetic Wnt surrogates and scaffold doping to target canonical Wnt. We conclude with a brief review of emerging technologies, such as mRNA therapy and Clustered Regularly Interspaced Short Palindromic Repeats technology, which serve as promising approaches for future clinical translation.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"961-976"},"PeriodicalIF":3.3,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.3349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5678742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Zwitterionic keratin coating on silk-Laponite fibrous membranes for guided bone regeneration","authors":"Matineh Atrian, Mahshid Kharaziha, Hanieh Javidan, Farzaneh Alihosseini, Rahmatallah Emadi","doi":"10.1002/term.3350","DOIUrl":"https://doi.org/10.1002/term.3350","url":null,"abstract":"<p>Implant-related infection is one of the main challenges in periodontal diseases. According to the zwitterionic properties of keratin, we aim to develop guided bone regeneration (GBR) membrane with antibacterial and bioactivity properties using a keratin coating. In this study, electrospun silk fibroin (SF)–Laponite (LAP) fibrous membranes were developed as GBR membranes, and keratin extracted from sheep wool was electrosprayed on them. Here, the role of electrospraying time (2, 3, and 4h) on the properties of the GBR membranes was investigated. After physicochemical characterization of the keratin-modified membranes, in vitro bioactivity and degradation rate of the membranes were studied in simulated body fluid and phosphate buffer saline, respectively. Moreover, proliferation and differentiation of mesenchymal stem cells were evaluated in contact with the keratin-modified SF–LAP membrane. Finally, the antibacterial activity of membranes against gram-positive bacteria (<i>Staphylococcus aureus</i>) was investigated. Results demonstrated the successful formation of homogeneous wool keratin coating on SF–LAP fibrous membranes using a simple electrospray process. While wool keratin coating significantly enhanced the elongation and hydrophilicity of the SF–LAP membrane, the mechanical strength was not changed. In addition, keratin coating significantly improved the bioactivity and degradation rate of SF–LAP membranes, owing to the carboxyl groups of amino acids in keratin coating. In addition, the synergic role of LAP nanoparticles and keratin coating drastically improved osteoblast proliferation and differentiation. Finally, the zwitterionic property of wool keratin coating originating from their equal positive (NH<sub>3</sub><sup>+</sup>) and negative (COO<sup>−</sup>) charges considerably improved the antibacterial activity of the SF–LAP membrane. Overall, keratin-coated SF–LAP fibrous membranes with significant mechanical and biological properties could have the potential for GBR membranes.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"1019-1031"},"PeriodicalIF":3.3,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6110967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Romanazzo, Chantal Kopecky, Shouyuan Jiang, Riddhesh Doshi, Vipul Mukund, Pallavi Srivastava, Jelena Rnjak-Kovacina, Kilian Kelly, Kristopher A. Kilian
{"title":"Biomaterials directed activation of a cryostable therapeutic secretome in induced pluripotent stem cell derived mesenchymal stromal cells","authors":"Sara Romanazzo, Chantal Kopecky, Shouyuan Jiang, Riddhesh Doshi, Vipul Mukund, Pallavi Srivastava, Jelena Rnjak-Kovacina, Kilian Kelly, Kristopher A. Kilian","doi":"10.1002/term.3347","DOIUrl":"https://doi.org/10.1002/term.3347","url":null,"abstract":"<p>Mesenchymal stem cell therapy has suffered from wide variability in clinical efficacy, largely due to heterogeneous starting cell populations and large-scale cell death during and after implantation. Optimizing the manufacturing process has led to reproducible cell populations that can be cryopreserved for clinical applications. Nevertheless, ensuring a reproducible cell state that persists after cryopreservation remains a significant challenge, and is necessary to ensure reproducible clinical outcomes. Here we demonstrate how matrix-conjugated hydrogel cell culture materials can normalize a population of induced pluripotent stem cell derived mesenchymal stem cells (iPSC-MSCs) to display a defined secretory profile that promotes enhanced neovascularization in vitro and in vivo. Using a protein-conjugated biomaterials screen we identified two conditions—1 kPa collagen and 10 kPa fibronectin coated polyacrylamide gels—that promote reproducible secretion of pro-angiogenic and immunomodulatory cytokines from iPSC-MSCs that enhance tubulogenesis of endothelial cells in Geltrex and neovascularization in chick chorioallantoic membranes. Using defined culture substrates alone, we demonstrate maintenance of secretory activity after cryopreservation for the first time. This advance provides a simple and scalable approach for cell engineering and subsequent manufacturing, toward normalizing and priming a desired cell activity for clinical regenerative medicine.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"1008-1018"},"PeriodicalIF":3.3,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.3347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5830105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aurélien Louvrier, Marie Kroemer, Lisa Terranova, Florent Meyer, Marion Tissot, Edouard Euvrard, Florelle Gindraux, Christophe Meyer, Gwena?l Rolin
{"title":"Development of a biomimetic bioreactor for regenerative endodontics research","authors":"Aurélien Louvrier, Marie Kroemer, Lisa Terranova, Florent Meyer, Marion Tissot, Edouard Euvrard, Florelle Gindraux, Christophe Meyer, Gwena?l Rolin","doi":"10.1002/term.3346","DOIUrl":"https://doi.org/10.1002/term.3346","url":null,"abstract":"<p>In the context of regenerative endodontics research with the development of biomaterials, this work aimed to develop and test a prototype biomimetic bioreactor of a human tooth. The bioreactor was designed to reproduce a shaped dental canal connected with a cavity reproducing the periapical region and irrigated through two fluidic channels intended to reproduce the apical residual vascular supply. A test biomaterial composed of polylactic acid/polycaprolactone-tannic acid (PLA/PCL-TA) was produced by electrospinning/electrospraying and calibrated to be inserted in a dental canal. This biomaterial was first used to evaluate its imbibition capacity and the oximetry inside the bioreactor. Then, Dental Pulp Stem Cells (DPSCs) were cultured on PLA/PCL-TA cones for 1–3 weeks in the bioreactor; afterward cell adhesion, proliferation, and migration were histologically assessed. Complete imbibition biomaterial was obtained in 10 min and oximetry was stable over time. In the bioreactor, DPSCs were able to adhere, proliferate and migrate onto the surface and inside the biomaterial. In conclusion, this bioreactor was used successfully to test a biomaterial intended to support pulp regeneration and constitutes a new in vitro experimental model closer to clinical reality.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 11","pages":"998-1007"},"PeriodicalIF":3.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6033448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}