Hyoeun Park, Woong Jin Cho, Jiseong Kim, Hyejong Choi, Inho Baek, Youngjin Kim, Deogil Kim, Byoung Ju Kim, Yoshie Arai, Soo-Hong Lee
{"title":"Stepwise Administration of Bone-Targeted Lipid Nanoparticles Encapsulating Valproic Acid and TUDCA Facilitates In Vivo Direct Reprogramming for Osteoporosis Treatment.","authors":"Hyoeun Park, Woong Jin Cho, Jiseong Kim, Hyejong Choi, Inho Baek, Youngjin Kim, Deogil Kim, Byoung Ju Kim, Yoshie Arai, Soo-Hong Lee","doi":"10.1007/s13770-025-00738-5","DOIUrl":"https://doi.org/10.1007/s13770-025-00738-5","url":null,"abstract":"<p><strong>Background: </strong>The ultimate goal of regenerative medicine is to restore damaged tissues to a healthy state in the body. Direct reprogramming, also referred to as transdifferentiation, holds significant therapeutic potential by converting abundant somatic cells, such as fibroblasts, into functionally distinct cell types for tissue regeneration. Despite its potential applications in regenerative medicine, direct reprogramming faces major challenges, including low efficiency and poor In vivo applicability. In this study, we propose a novel therapeutic strategy for osteoporosis based on In vivo direct reprogramming using a stepwise delivery approach that first enhances cellular stemness and subsequently induces osteogenic transdifferentiation. Enhancing stemness in lineage-committed cells facilitates their conversion into other functional cell types.</p><p><strong>Method: </strong>To investigate the efficiency of direct reprogramming via stepwise delivery, we utilized valproic acid (VPA) and tauroursodeoxycholic acid (TUDCA) as reprogramming and bone-stimulating factors, respectively. VPA increased the expression of stemness genes, including Oct4, Nanog, and Sox2, and subsequent treatment of TUDCA enhanced the expression of osteogenic genes in the mouse fibroblast. Targeted delivery of these factors to fibroblasts surrounding bone tissue, enabling subsequent direct reprogramming into osteoblasts, was achieved using bisphosphonate (BP)-conjugated lipid nanoparticles as carriers.</p><p><strong>Results: </strong>Our findings demonstrate that sequential induction of cell reprogramming and tissue regeneration through stepwise administration of VPA and TUDCA significantly enhances therapeutic efficacy in a mouse model of osteoporosis compared to their simultaneous administration.</p><p><strong>Conclusion: </strong>This stepwise bone-targeted drug delivery system presents a promising strategy for osteoporosis treatment via In vivo direct reprogramming.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cha Yeon Kim, Cholong Jeong, Hun Lee, Changmo Hwang
{"title":"Corneal Endothelium Regeneration with Decellularized Porcine Corneal Extracellular Matrix Scaffolds.","authors":"Cha Yeon Kim, Cholong Jeong, Hun Lee, Changmo Hwang","doi":"10.1007/s13770-025-00734-9","DOIUrl":"https://doi.org/10.1007/s13770-025-00734-9","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the structural, biochemical, and functional performance of decellularized porcine corneal extracellular matrix (dECM) scaffolds for engineering human corneal endothelium.</p><p><strong>Methods: </strong>Porcine corneas were decellularized using either 0.3% sodium dodecyl sulfate (SDS) or 1.5 M sodium chloride (NaCl), followed by enzymatic nucleic acid digestion. Histological and biochemical analyses were performed to assess decellularization efficiency and extracellular matrix preservation. Human corneal endothelial cells (hCECs) were cultured on SDS-dECM scaffolds to evaluate cytocompatibility, morphology, and functional outcomes. Therapeutic efficacy was further assessed using a rabbit model of corneal endothelial dystrophy (CED).</p><p><strong>Results: </strong>SDS-treated corneas showed superior nuclear clearance (residual DNA: 123.60 ± 8.92 ng/mg) compared to NaCl (146.15 ± 5.49 ng/mg), with 95.2% retention of sulfated glycosaminoglycans (sGAGs) and moderate collagen loss (40% of native). In contrast, NaCl better preserved collagen (100% of native) but exhibited incomplete decellularization and lower sGAG retention (71.0%). In vitro, hCECs cultured on SDS-dECM exhibited progressive proliferation, with cell viability surpassing that of TCPS by day 14 (389.01 ± 5.68 vs. 359.65 ± 7.92, p < 0.05). Immunofluorescence confirmed polygonal morphology and ZO-1 expression, indicating intact barrier phenotype. Transparency of dECM scaffolds improved with hCEC culture, with light transmittance at 400 nm increasing from 65.82% (acellular) to 90.13% (double-sided culture). In vivo transplantation of hCEC-seeded SDS-dECM resulted in dose-dependent corneal clarity restoration, with the high-dose group achieving transparency and pachymetry comparable to normal corneas (thickness ~ 602 µm, grading score 0.00 ± 0.00) by 16 weeks.</p><p><strong>Conclusions: </strong>SDS-dECM scaffolds demonstrated excellent biocompatibility and functional support for human corneal endothelial cells, both in vitro and in vivo. These findings support their potential use as bioengineered alternatives to donor corneas for treating endothelial dysfunction.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas A Chartrain, Marina V Pryzhkova, Juliana I Candelaria, Kristin H Gilchrist, Philip W Jordan
{"title":"An Efficient Organoid Cutting Method for Long-Term Culture and High-Throughput Analyses.","authors":"Nicholas A Chartrain, Marina V Pryzhkova, Juliana I Candelaria, Kristin H Gilchrist, Philip W Jordan","doi":"10.1007/s13770-025-00731-y","DOIUrl":"https://doi.org/10.1007/s13770-025-00731-y","url":null,"abstract":"<p><strong>Background: </strong>Human organoid models are invaluable for developmental studies, disease modeling, and personalized medicine research. However, long-term maintenance is challenging due to hypoxia and nutrient limitations as organoids grow. Cutting organoids improves viability, but current methods have low throughput and are prone to causing culture contamination. This study introduces an efficient organoid cutting method to enhance long-term culture and enable high-throughput analyses.</p><p><strong>Methods: </strong>We employed three-dimensional (3D) printing to fabricate four classes of organoid cutting jigs with blade guides that were compared and optimized for consistent sectioning of human pluripotent stem cell (hPSC)-derived organoids. Organoids were cultured in mini-spin bioreactors and cut every three weeks, beginning on day 35. Organoid health and growth were evaluated by size increase and proliferative marker expression. Additionally, we utilized 3D printed molds to create GelMA or Geltrex-embedded organoid arrays and silicone molds for optimal cutting temperature compound (OCT)-embedding of organoid arrays.</p><p><strong>Results: </strong>All 3D printed jigs enabled rapid and uniform organoid cutting under sterile conditions. We determined that a flat-bottom cutting jig design had superior cutting efficiency. Cutting improved nutrient diffusion, increased cell proliferation, and enhanced organoid growth during long-term culture. The mold-based approaches enabled the creation of densely packed organoid arrays and cryosections with evenly distributed organoids.</p><p><strong>Conclusion: </strong>This novel organoid cutting and arraying method overcomes limitations in long-term organoid culture and high-throughput processing. The simplicity of the cutter design and handling make it a versatile tool for diverse types of organoids. By enhancing organoid viability and enabling consistent sample preparation, this approach facilitates improved organ development and disease modeling, drug screening, and high-throughput analyses, including single-cell spatial transcriptomics applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PTH Promotes Chondrogenesis of Fibrocartilage Stem Cells and Alleviates Temporomandibular Joint Osteoarthritis.","authors":"Zhihang Yue, Wuyi Gong, Haojun Chu, Yongming Li","doi":"10.1007/s13770-025-00723-y","DOIUrl":"https://doi.org/10.1007/s13770-025-00723-y","url":null,"abstract":"<p><strong>Background: </strong>Parathyroid hormone (PTH) can promote subchondral bone formation and alleviate temporomandibular joint (TMJ) osteoarthritis (OA), but the effects of PTH on fibrocartilage stem cells (FCSCs) in cartilage surfaces have yet to be studied.</p><p><strong>Methods: </strong>We established the TMJOA model in rats and administered PTH to treat them. Rat condyles were analyzed using micro-computed tomography, histological, and immunohistochemical staining. To study PTH's effects on FCSCs in vitro, we employed quantitative polymerase chain reaction, Western Blot, and immunofluorescence staining. We also constructed the TMJOA model in tdTomato; Cathepsin K (Ctsk)-Cre mice and rescued them with PTH. EdU and immunofluorescence staining were used to measure the proliferation and chondrogenic differentiation of FCSCs in vivo. Furthermore, after discectomy, we injected diphtheria toxin (DT) into the Ctsk-Cre; diphtheria toxin receptor (DTR) mice to ablate FCSCs. Afterwards, PTH was injected, and we evaluated the Collagen Type II Alpha 1 (COL2A1)-positive area using immunofluorescence staining.</p><p><strong>Results: </strong>We successfully developed a TMJOA model, and after treatment with PTH, the rat condyles' BV/TV and Tb. Th increased, and the expression of chondrogenic-related genes was elevated. Additionally, PTH promoted the chondrogenic differentiation of FCSCs in vitro. In tdTomato; Ctsk-Cre mice, the Ctsk/EdU and Ctsk/COL2A1 double-positive cells were increased after PTH administration. Moreover, after the ablation of FCSCs by DT, the effects of PTH treatment were notably reduced.</p><p><strong>Conclusion: </strong>PTH promotes the proliferation and chondrogenic differentiation of condylar FCSCs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sunhyung Lee, Jinwoo Nam, Hong Seok Kim, Jeong Joon Yoo
{"title":"Phenotype-Preserving Co-culture of Osteoblasts and Chondrocytes Enhances Bone-Cartilage Interface Integration in a PRP-Augmented Scaffold.","authors":"Sunhyung Lee, Jinwoo Nam, Hong Seok Kim, Jeong Joon Yoo","doi":"10.1007/s13770-025-00727-8","DOIUrl":"https://doi.org/10.1007/s13770-025-00727-8","url":null,"abstract":"<p><strong>Background: </strong>Effective bone-cartilage integration remains a challenge in orthopedic surgery. Conventional methods often fail to reconstruct the native osteochondral interface. This study explores a scaffold-mediated approach utilizing co-cultured osteoblasts and chondrocytes, with platelet-rich plasma (PRP) as a potential promotor for bone-cartilage interface healing.</p><p><strong>Methods: </strong>We developed a co-culture system integrating both osteoblasts and chondrocytes on PLGA scaffolds, either with or without PRP supplementation. Cell phenotype maintenance was evaluated by RT-PCR, while morphological analysis was performed by scanning electron microscopy and fluorescence microscopy. To assess healing potential, we created a gap-mimic construct comprising bone, scaffold, and cartilage layers, which was implanted subcutaneously in BALB/c-nude mice. Gap healing was evaluated at 4 and 8 weeks through macroscopic examination, quantitative adhesion analysis, and histological assessment of cellular invasion.</p><p><strong>Results: </strong>Co-cultured osteoblasts and chondrocytes maintained their phenotypes on PLGA scaffolds, with PRP significantly enhancing cell adhesion (215% increase for chondrocytes, 120% for osteoblasts) and proliferation. In vivo, cell-containing scaffolds demonstrated significantly greater attachment at the bone-cartilage interface compared to acellular constructs. PRP-treated scaffolds exhibited higher attachment rates (82.3% vs 76.7%) and cellular invasion (5/6 vs 3/6 constructs) at 8 weeks, with invasion observed as early as 4 weeks in the PRP group, suggesting accelerated remodeling.</p><p><strong>Conclusion: </strong>This study demonstrates the feasibility of developing transplantable scaffolds containing co-cultured osteoblasts and chondrocytes while preserving their phenotypes. These scaffolds exhibit significant potential in promoting healing at the bone-cartilage interface, with PRP further enhancing proliferation and improving the scaffold's ability to promote bone-cartilage interface healing.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic Effect of Stromal Vascular Fraction and Lymph Node Transfer in a Rabbit Hindlimb Model.","authors":"Jaemin Lee, Jihyun Kim, Jeong-Hyun Cheon, Hyung-Chul Lee, Jae-Ho Chung, Eul-Sik Yoon","doi":"10.1007/s13770-025-00728-7","DOIUrl":"https://doi.org/10.1007/s13770-025-00728-7","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs) promote lymphangiogenesis, though their integration with vascularized lymph node transfer (VLNT) is not well-explored. Unlike ADSCs, the stromal vascular fraction (SVF) can be obtained intraoperatively without the need for cell culture, making it ideal for incorporation into VLNT in a single-stage surgical procedure. This study evaluates the impacts of combined VLNT and SVF therapy using a rabbit hindlimb model.</p><p><strong>Method: </strong>New Zealand white rabbits were divided into four groups: control, VLNT only, SVF only, and combined VLNT plus SVF. The VLNT procedure involved transferring a pedicled lymph node flap, while the SVF was harvested and injected into the perinodal tissue. Postoperative assessments included measuring edema volume, performing ICG lymphography, conducting histological analysis, and measuring VEGF-C and LYVE-1 expression.</p><p><strong>Results: </strong>Initial increases in hindlimb edema volume were noted, but a significant decrease occurred by week 4, particularly in the VLNT group and VLNT plus SVF group compared to the control group. Histological evaluations indicated that the combined treatment group preserved superior structural integrity of the lymph nodes, with a decreased proportion of fibroadipose tissue compared to the VLNT-only group. Elevated VEGF-C expression was observed in the SVF-treated groups, as confirmed by both RT-PCR and ELISA analyses at week 4. Additionally, the combined VLNT plus SVF group showed increased LYVE-1 expression by week 8.</p><p><strong>Conclusion: </strong>The results suggest that SVF can be effectively integrated with VLNT in a single-stage procedure, enhancing the viability and structural integrity of vascularized lymph nodes. These results highlight the potential of this combined approach as a promising therapeutic strategy for advanced-stage lymphedema, meriting further exploration in clinical trials.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strategies for the Patient-Specific Implant Angle of Bone Scaffolds Using Optimization.","authors":"Jun Won Choi, Jung Jin Kim","doi":"10.1007/s13770-025-00730-z","DOIUrl":"https://doi.org/10.1007/s13770-025-00730-z","url":null,"abstract":"<p><strong>Background: </strong>Bone scaffolds are artificial structures used for restoring bone functionality via the reconstruction and repair of bone tissue. Although these scaffolds interact seamlessly with the surrounding tissue, conventional scaffold designs often fail to consider the microstructure of the surrounding bone, leading to reduced mechanical performance. This study proposed an implantation angle optimization approach for bone scaffolds that considers the microstructures around the implant, thus improving the mechanical properties of commonly used scaffolds.</p><p><strong>Method: </strong>This study proposed a novel method for optimizing the implantation angle of bone scaffolds, thereby enhancing their mechanical performance and integration with the surrounding bone tissue. A finite element model based on the imaging data of the bone scaffold within the skeletal system was constructed. Then, the structural behavior under external load was analyzed to determine the optimal implantation angle by rotating the bone scaffold.</p><p><strong>Result: </strong>Bone scaffolds with optimized angles show up to 7.53% strain energy difference between the scaffold and native bone, which improves load transfer and supports more natural bone remodeling. These results suggest that this approach enhances scaffold stability and reduces the risk of implant failure.</p><p><strong>Conclusion: </strong>The results highlight the potential of the proposed approach to optimize the implantation angle considering the bone microstructure, thus significantly enhancing scaffold performance. The combination of these strategies shows significant potential for advancing bone-repair solutions and improving patient outcomes in orthopedic surgeries.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanofiber-Based Biomimetic Platforms for Chronic Wound Healing: Recent Innovations and Future Directions.","authors":"Mina Kwon, Ki Su Kim","doi":"10.1007/s13770-025-00729-6","DOIUrl":"https://doi.org/10.1007/s13770-025-00729-6","url":null,"abstract":"<p><strong>Background: </strong>Wound healing remains a significant challenge in healthcare, particularly for complex and chronic wounds where conventional treatments often fail to provide effective solutions. Recent advances in nanofiber technology have opened new avenues for wound management by offering biomimetic structures that support tissue regeneration. Due to their high surface area-to-volume ratio and porosity, nanofibers closely resemble the extracellular matrix, facilitating an optimal environment for cell adhesion, proliferation, and differentiation.</p><p><strong>Methods: </strong>This review examines the role of nanofiber-based wound dressings, highlighting their unique advantages in drug delivery, moisture retention, and antimicrobial protection. Additionally, emerging trends such as smart wound dressings responsive to environmental stimuli and multifunctional nanofiber systems are discussed.</p><p><strong>Results and conclusion: </strong>Nanofiber technology has demonstrated significant potential in enhancing wound healing outcomes by providing an advanced platform for therapeutic delivery and tissue regeneration. Furthermore, the integration of nanofibers with artificial intelligence and biotechnology offers promising directions for future research. As these innovations continue to evolve, nanofiber-based wound dressings may revolutionize wound care by enabling more personalized and effective treatment strategies.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current Status of Stromal Vascular Fraction from Adipose Tissue in the Clinical Application for Osteoarthritis Treatment.","authors":"Gun-Il Im","doi":"10.1007/s13770-025-00722-z","DOIUrl":"https://doi.org/10.1007/s13770-025-00722-z","url":null,"abstract":"<p><strong>Background: </strong>Recently, regenerative medicine based on cell-based therapies has emerged as a therapeutic possibility for the management of osteoarthritis (OA). Stromal vascular fraction (SVF) is a cellular mixture obtained from lipoaspirate processed through either mechanical or enzymatic separation. SVF has been applied in several countries to treat OA patients without robust supporting evidence or comprehensive evaluation.</p><p><strong>Methods: </strong>This review purposes to summarize clinical evidence regarding SVF as a therapeutic for OA and to introduce the author's perspective. Eleven studies were found suitable for this review; out of these, seven were randomized clinical trials and four were cohort studies.</p><p><strong>Results: </strong>A review of controlled studies suggests that SVF may offer better symptomatic relief than placebo or hyaluronic acid in the long term, and the effect of SVF is comparable to that of bone marrow aspirate concentrates.</p><p><strong>Conclusion: </strong>Prospective studies with improved control over the cell isolation method, dosage, and patient selection are necessary to provide convincing evidence of the benefits of SVF in treating OA.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}