Model Of Regeneration Research Articles

Modeling and analysis of air combustion and steam regeneration in methanol to olefins processes

Light olefins is the incredibly important materials in chemical industry. Methanol to olefins (MTO), which provides a non-oil route for light olefins production, received considerable attention in the past decades. However, the catalyst deactivation is an inevitable feature in MTO processes, and regeneration, therefore, is one of the key steps in industrial MTO processes. Traditionally the MTO catalyst is regenerated by removing the deposited coke via air combustion, which unavoidably transforms coke into carbon dioxide and reduces the carbon utilization efficiency. Recent study shows that the coke species over MTO catalyst can be regenerated via steam, which can promote the light olefins yield as the deactivated coke species can be essentially transferred to industrially useful synthesis gas, is a promising pathway for further MTO processes development. In this work, we modelled and analyzed these two MTO regeneration methods in terms of carbon utilization efficiency and technology economics. As shown, the steam regeneration could achieve a carbon utilization efficiency of 84.31%, compared to 74.74% for air combustion regeneration. The MTO processes using steam regeneration can essentially achieve the near-zero carbon emission. In addition, light olefins production of the MTO processes using steam regeneration is 12.81% higher than that using air combustion regeneration. In this regard, steam regeneration could be considered as a potential yet promising regeneration method for further MTO processes, showing not only great environmental benefits but also competitive economic performance.

Decellularized tracheal scaffold as a promising 3D scaffold for tissue engineering applications

Tissue engineering is a science that uses the combination of scaffolds, cells, and active biomolecules to make tissue in order to restore or maintain its function and improve the damaged tissue or even an organ in the laboratory. The purpose of this research was to study the characteristics and biocompatibility of decellularized sheep tracheal scaffolds and also to investigate the differentiation of Adipose-derived stem cells (AD-MSCs) into tracheal cells. After the decellularization of sheep tracheas through the detergent-enzyme method, histological evaluations, measurement of biochemical factors, measurement of DNA amount, and photographing the ultrastructure of the samples by scanning electron microscopy (SEM), they were also evaluated mechanically. Further, In order to check the viability and adhesion of stem cells to the decellularized scaffolds, adipose mesenchymal stem cells were cultured on the scaffolds, and the 3-(4,5-dimethylthiazol-2-yl)− 2,5-diphenyltetrazolium bromide (MTT) assay was performed. The expression analysis of the intended genes for the differentiation of mesenchymal stem cells into tracheal cells was evaluated by the real-time PCR method. These results show that the prepared scaffolds are an ideal model for engineering applications, have high biocompatibility, and that the tracheal scaffold provides a suitable environment for the differentiation of ADMSCs. This review provides a basis for future research on tracheal decellularization scaffolds, serves as a suitable model for organ regeneration, and paves the way for their use in clinical medicine.

PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish

Despite the robust regenerative capacity of the liver, prolonged and severe liver damage impairs liver regeneration, leading to liver failure. Since the liver co-opts the differentiation of liver progenitor cells (LPCs) into hepatocytes to restore functional hepatocytes, augmenting LPC-mediated liver regeneration may be beneficial to patients with chronic liver diseases. However, the molecular mechanisms underlying LPC-to-hepatocyte differentiation have remained largely unknown. Using the zebrafish model of LPC-mediated liver regeneration, Tg(fabp10a:pt-β-catenin), we present that peroxisome proliferator-activated receptor-alpha (PPARα) activation augments LPC-to-hepatocyte differentiation. We found that treating Tg(fabp10a:pt-β-catenin) larvae with GW7647, a potent PPARα agonist, enhanced the expression of hepatocyte markers and simultaneously reduced the expression of biliary epithelial cell (BEC)/LPC markers in the regenerating livers, indicating enhanced LPC-to-hepatocyte differentiation. Mechanistically, PPARα activation augments the differentiation by suppressing YAP signaling. The differentiation phenotypes resulting from GW7647 treatment were rescued by expressing a constitutively active form of Yap1. Moreover, we found that suppression of YAP signaling was sufficient to promote LPC-to-hepatocyte differentiation. Treating Tg(fabp10a:pt-β-catenin) larvae with the TEAD inhibitor K-975, which suppresses YAP signaling, phenocopied the effect of GW7647 on LPC differentiation. Altogether, our findings provide insights into augmenting LPC-mediated liver regeneration as a regenerative therapy for chronic liver diseases.

Co-creation of community micro-renewals: Model analysis and case studies in Shanghai, China

Community micro-renewal is an important aspect of urban regeneration. Residents, as the primary users of the community, have become a vital component of community micro-renewals. With the advent of participatory design, designers are no longer the dominant constructors of communities. Residents' participation is essential to current community micro-renewals, but the existing resident involvement still reflects a lack of initiative and an underutilization of potential. Instead, co-creation, in which residents can be deeply involved in the community micro-renewals, is becoming the mainstream. This paper categorizes co-creation models in community micro-renewals into three types according to the degree of residents' participation: the co-creation model based on common ideation, the co-creation model for resident participation in the design process, and the co-creation model of resident-led community regeneration. Three corresponding cases in Shanghai, China are analyzed in relation to specific scenarios and typologies. Each case study provides a contextualized interpretation of the characteristics associated with different types of co-creation. Increased residents' participation in the process of co-creation has been found to positively impact residents’ identification with community micro-renewals and their intrinsic commitment to sustain them. Furthermore, highly participatory co-creation empowers residents to assume a higher level of responsibility for the project and mitigates the risk of uniformity. The contribution of this paper is to provide a theoretical basis for subsequent practices. Specifically, this research aims to facilitate a comprehensive integration of participatory design methodologies with community micro-renewal initiatives.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Epimorphic regeneration in the mammalian tympanic membrane

Adult mammals are generally believed to have limited ability to regenerate complex tissues and instead, repair wounds by forming scars. In humans and across mammalian species, the tympanic membrane (TM) rapidly repairs perforations without intervention. Using mouse models, we demonstrate that the TM repairs itself through a process that bears many hallmarks of epimorphic regeneration rather than typical wound healing. Following injury, the TM forms a wound epidermis characterized by EGFR ligand expression and signaling. After the expansion of the wound epidermis that emerges from known stem cell regions of the TM, a multi-lineage blastema-like cellular mass is recruited. After two weeks, the tissue architecture of the TM is largely restored, but with disorganized collagen. In the months that follow, the organized and patterned collagen framework of the TM is restored resulting in scar-free repair. Finally, we demonstrate that deletion of Egfr in the epidermis results in failure to expand the wound epidermis, recruit the blastema-like cells, and regenerate normal TM structure. This work establishes the TM as a model of mammalian complex tissue regeneration.

Fabrication of wound dressings: Herbal extract-loaded nanoliposomes embedded in fungal chitosan/polycaprolactone electrospun nanofibers for tissue regeneration.

Wound healing is a complex process and one of the major therapeutic and economic subjects in the pharmaceutical area. In recent years, the fabrication of nano-sized wound dressing models has attracted great attention for tissue regeneration. Plant extracts loaded nanoparticles are environmentally friendly and non-toxic and the release of the bioactive substance will be controlled to the wound area. This study aims to fabricate wound dressing models that contain bioactive components for tissue regeneration. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extracts loaded nanoliposomes were prepared, characterized, and embedded in nanofiber structures. The effectiveness of wound dressing models for tissue regeneration was evaluated by in vitro and in vivo studies. It was observed that all wound dressing models positively affect the cell viability of human dermal fibroblast cells. It was determined that plant extracts loaded nanoparticles embedded in nanofibers increased in cell viability than nanoparticles that were non-embedded in nanofiber structures. Histological analysis showed that plant extract-loaded nanoliposomes embedded in chitosan/PCL nanofibers were used for tissue regeneration. The most effective nanofibers were determined as Wd-ClNL nanofibers. RESEARCH HIGHLIGHTS: Hypericum perforatum L. and Cistus laurifolius L. were prepared by modified ultrasonic extraction method. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extract-loaded nanoliposomes were prepared, and characterized. They were embedded in chitosan/polycaprolactone nanofiber. Effects of the wound dressing model were analyzed by in vitro and in vivo assays for tissue regeneration.

Elongation of very long chain fatty acids-3 (Elovl3) is activated by ZHX2 and is a regulator of cell cycle progression.

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 targets become dysregulated in liver damage, we investigated the relationship between Zhx2 and Elovl3 in liver development, damage, and regeneration. Here, using mouse and cell models, we demonstrate that Zhx2 positively regulates Elovl3 expression in the liver and that male-biased hepatic Elovl3 expression is established between 4 and 8 wk of age in mice. Elovl3 is dramatically repressed in mouse models of liver regeneration, and the reduced Elovl3 levels in the regenerating liver are associated with changes in hepatic VLCFAs. Human hepatoma cell lines with forced Elovl3 expression have lower rates of cell growth; analysis of synchronized cells indicates that this reduced proliferation correlates with cells stalling in S-phase and lower mRNA levels of cell cyclins. Taken together, these data indicate that Elovl3 expression helps regulate cellular proliferation during liver development and regeneration, possibly through control of VLCFAs.NEW & NOTEWORTHY Numerous targets of the transcription factor Zhx2 are dysregulated in liver disease. We show that the elongase Elovl3 is a novel Zhx2 target. Elovl3 and Zhx2 expression change during liver regeneration, which is associated with changes in very long chain fatty acids. Forced Elovl3 expression reduces cell growth and blocks cell cycle progression. This suggests that Elovl3 may account, at least in part, for the relationship between Zhx2 and proliferation during liver development and disease.

Unravelling hierarchical patterning of biomaterial inks with 3D microfluidic-assisted spinning: a paradigm shift in bioprinting technologies

For decades, 3D bioprinting has offered a revolutionising approach to combine living cells and biomaterials to engineer complex, yet functional constructs. However, traditional 3D bioprinting platforms fall short of the ability to pattern complex gradients of biomaterials, cells, and ultimately bio-physical properties to drive tissue formation and regeneration. Recently, 3D microfluidic-assisted bioprinting (3DMB) has risen as a new hybrid approach for the fabrication of physiologically relevant tissues, adopting a microfluidic chip as functional printhead to achieve hierarchical patterning of bioinks and precise control over the microscale architecture of printed constructs, enabling the creation of multi-layered tissues. This review explores recent advancements in graded biomaterial patterning using microfluidic-assisted spinning and novel 3D bioprinting technologies. The physiological hierarchical arrangement of human tissues and the crucial role of biomaterials in achieving ordered assembly is hereby discussed. Lastly, the integration of microfluidic-assisted techniques with new bioprinting platforms is highlighted, examining the latest advancements in tissue regeneration and disease modelling.

Toxicity assessment of microcystin-leucine arginine in planarian Dugesia japonica.

Microcystin-leucine arginine (MC-LR), a representative cyanobacterial toxin, poses an increasing and serious threat to aquatic ecosystems. Despite investigating its toxic effects in various organisms and cells, the toxicity to tissue regeneration and stem cells in vivo still needs to be explored. Planarians are ideal regeneration and toxicology research models and have profound implications in ecotoxicology evaluation. This study conducted a systemic toxicity evaluation of MC-LR, including morphological changes, growth, regeneration, and the underlying cellular and molecular changes after MC-LR exposure, which were investigated in planarians. The results showed that exposure to MC-LR led to time- and dose-dependent lethal morphological changes, tissue damage, degrowth, and delayed regeneration in planarians. Furthermore, MC-LR exposure disturbed the activities of antioxidants, including total superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, and total antioxidant capacity, leading to oxidative stress and DNA damage, and then reduced the number of dividing neoblasts and promoted apoptosis. The results demonstrated that oxidative stress and DNA damage induced by MC-LR exposure caused apoptosis. Excessive apoptosis and suppressed neoblast activity led to severe homeostasis imbalance. This study explores the underlying mechanism of MC-LR toxicity in planarians and provides a basis for the toxicity assessment of MC-LR to aquatic organisms and ecological risk evaluation.

Mechanisms of Regeneration and Fibrosis in the Endometrium.

The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.

Cells transiently expressing periostin are required for intramedullary intramembranous bone regeneration

Intramembranous bone regeneration plays an important role in fixation of intramedullary implants used in joint replacement and dental implants used in tooth replacement. Despite widespread recognition of the importance of intramembranous bone regeneration in these clinical procedures, the underlying mechanisms have not been well explored. A previous study that examined transcriptomic profiles of regenerating bone from the marrow space showed that increased periostin gene expression preceded increases in several osteogenic genes. We therefore sought to determine the role of cells transiently expressing periostin in intramedullary intramembranous bone regeneration. We used a genetic mouse model that allows tamoxifen-inducible fluorescent labeling of periostin expressing cells. These mice underwent ablation of the bone marrow cavity through surgical disruption, a well-established intramembranous bone regeneration model. We found that in intact bones, fluorescently labeled cells were largely restricted to the periosteal surface of cortical bone and were absent in bone marrow. However, following surgical disruption of the bone marrow cavity, cells transiently expressing periostin were found within the regenerating tissue of the bone marrow compartment even though the cortical bone remained intact. The source of these cells is likely heterogenous, including cells occupying the periosteal surface as well as pericytes and endothelial cells within the marrow cavity. We also found that diphtheria toxin-mediated depletion of cells transiently expressing periostin at the time of surgery impaired intramembranous bone regeneration in mice. These data suggest a critical role of periostin expressing cells in intramedullary intramembranous bone regeneration and may lead to novel therapeutic interventions to accelerate or enhance implant fixation.

Characteristics of a gill resection – Regeneration model in freshwater laboratory-reared Atlantic salmon (Salmo salar)

Impaired gill function is a critical issue in aquaculture due to factors such as poor water quality, disease, and farm management practices which can greatly compromise gill integrity and ultimately fish growth and survival. Regeneration of damaged gill tissue has been reported for some fish species, however, little is known about Atlantic salmon, which is one of the most economically important salmonid species. This study investigated the regenerative capability of gill tissue following resection in post-smolt Atlantic salmon reared in fresh water. Fish were subjected to two levels of resection severity: 30% or 50% of filament length. Changes in filament length and the cytological and functional capacity of regenerated tissue were studied at several time points post-resection (PR). On average, 38% ± 3.89 of the resected filament length regenerated in both resected groups at week-20 PR. However, absolute regeneration (mm) in 50% resected filaments was greater as compared to the 30% resected filaments. In both groups, regeneration percentage was significantly different among individuals, but was not correlated with initial body size, condition factor, or overall fish growth rate. Immunohistochemistry showed an increase in cell proliferation at the filament tip shortly after resection followed by the appearance of ionocytes, chemoreceptive neuroepithelial cells (NECs), and nerve fibres at week-4 PR. In both resected groups >50% and 90% of NECs were innervated by week-12 and -20 PR, respectively. Gill Na+/K+-ATPase activity in regenerated tissue was not significantly different from that of internal control and non-resected control fish. Our results demonstrate significant regeneration and apparent functional recovery of resected gill filaments in Atlantic salmon which has important implications for recovery from gill damage and developing best practices for maintenance of gill health of farmed salmon.

A Narrative Review on Oral Mucosa Biomechanics and Clinical Implications of Periodontal and Implant-Related Regenerative Procedures.

Healing outcomes of periodontal and implant-related regenerative procedures are closely related to wound stability, which is partially determined by biomechanical properties and behaviors of oral mu- cosal tissues. Studies on soft tissue behavior under biomechanical forces in oral regeneration models are scarce. Thus, this review aims to (1) contrast the microstructural differences between the attached gingiva (AM) and lining (LM) mucosa; (2) evaluate biomechanical behaviors of the two mucosal types; and (3) relate residual flap tension to the prevalence of wound opening after regenerative procedures. Compositional and structural differences between the AM and LM explain their biomechanical property differences. Wound destabilizers, including tissue recoil stemming from its viscoelastic property, muscle pull, and inflammatory edema (created after the flap-releasing procedure for primary wound closure) in- terfere with wound stability. Residual flap tension < 0.05 N is a prerequisite for sustained wound closure. Tissues under stress can exert negative cellular changes, resulting in necrosis and wound dehiscence. Biomechanical properties and the variations between AM and LM dictate the degree of wound stability. Efforts should be made to reduce the negative impact of the potential destabilizers to optimize wound stability.

Pb inhibited C2C12 myoblast differentiation by regulating HDAC2

Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Lead (Pb) exposure impaired the development and the health of bones, which slows the growth of children. However, it is far from clear what exactly the effects of Pb on skeletal muscle development are. In this study, C2C12 cells are commonly used as an in vitro model of muscle regeneration due to their ability to transition from a proliferative phase into differentiated myofibers. The dose of 1, 5, and 10 μM Pb were adopted to study the toxicity of Pb on C2C12 proliferation and differentiation. First, the effects of Pb on cell viability were detected and the results demonstrated that 5 μM and 10 μM Pb exposure decreased cell viability, while 1 μM Pb exposure has no obvious effects on cell viability. Then, 1–10 μM Pb exposure seriously reduced the C2C12 myoblasts differentiation, with the decrease of myogenic differentiation marker genes expression, including Muscle creatine kinase (MCK), Myosin Heavy Chain 4 (MYH4), Myogenin (MYOG), Myogenic Differentiation (MYOD). What’s more, it was found that the epigenetic modifier histone deacetylase-2 (HDAC2) was upregulated after Pb exposure on C2C12 myoblasts. Further studies conclusively showed knockdown of HDAC2 ameliorated Pb-damaged C2C12 myoblasts differentiation, indicating HDAC2 plays a vital role in the Pb-induced C2C12 myoblasts differentiation deficits. In summary, these results demonstrated that Pb exposure inhibited C2C12 myoblasts differentiation by regulating HDAC2.

Institutionalization of public interest in planning: Evolving mechanisms of public representation in China’s urban regeneration policymaking

How to capture, represent, and materialize public interest in urban planning has gone through multiple rounds of experimentation, crystallizing a number of regulatory regimes of planning in different historical and political-economic contexts. However, how to define the “public” and capture the public interest in urban planning remains problematic in both planning practices and democratic theory. Therefore, drawing upon Dewey and Habermas’s view of the public sphere, this paper introduces a scale perspective to examine the subjects in planning and the power framing process in defining the public in urban regeneration policymaking. First, this paper revisits the current debates on the concept of public interest and identifies three interpretations of public interest materialization: utilitarian, unitary, and communicative. Second, this paper illustrates the institutionalization process of public interest in China’s urban planning system. We critically examine the evolving mechanisms of public representation in China’s urban regeneration policymaking since 1949. The institutionalization of public interest in China shows distinguished trajectories from the Western countries. These differences are caused by different values that define the scale of “public” in different socio-political contexts. Given the emerging communicative turn in China, we found a hybrid norm of public interest as reflected in the recent “co-production” model of urban regeneration. The contribution of this paper is threefold: 1) highlights the validity of the public interest concept by introducing a scale sensitivity to analyze the subjects in planning; 2) complements public interest typology by identifying a hybrid norm in China that weaves between unitary and communicative interpretations; 3) revisits Dewey’s democratization theory by conceptualizing the institutionalization of public interest in semi-authoritarian China that is determined across the scales of subjects in planning, the ever-changing political-economic contexts, and the planning application in established rules.

Biological performance of a novel bovine hydroxyapatite in a guided bone regeneration model: A preclinical study in a mandibular defect in dogs.

This preclinical model study aims to evaluate the performance and safety of a novel hydroxyapatite biomaterial (Wishbone Hydroxyapatite, WHA) on guided bone regeneration compared to a commercially available deproteinized bovine bone mineral (Bio-Oss, BO). Twenty-four beagle dogs were allocated to three timepoint cohorts (4, 12, and 26 weeks) of eight animals each. In all animals, four critical-sized, independent wall mandibular defects were created (32 defects/cohort). Each animal received all four treatments, allocated randomly to separated defects: WHA + collagen membrane (M), BO + M, no treatment (Sham, Sh), and Sh + M. At each timepoint, the specimens were harvested for histologic and histomorphometric analyses to determine the newly formed bone and osteoconductivity. At 4 weeks, bone regeneration was significantly higher for WHA + M (46.8%) when compared to BO + M (21.4%), Sh (15.1%), and Sh + M (23.1%) (p < 0.05); at 12 and 26 weeks, regeneration was similar for WHA and BO. Bone-to-material contact increased over time similarly for WHA + M and BO + M. From a safety point of view, inflammation attributed to WHA + M or BO + M was minimal; necrosis or fatty infiltrate was absent. WHA + M resulted in higher bone regeneration rate than BO + M at 4 weeks. Both BO + M and WHA + M were more efficient than both Sh groups at all timepoints. Safety and biocompatibility of WHA was favorable and comparable to that of BO.

Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii

BackgroundRestorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regeneration in this major group remains a key goal. Among annelids, the nereididae Platynereis dumerilii (re)emerged recently as a front-line regeneration model. Following amputation of its posterior part, Platynereis worms can regenerate both differentiated tissues of their terminal part as well as a growth zone that contains putative stem cells. While this regeneration process follows specific and reproducible stages that have been well characterized, the transcriptomic landscape of these stages remains to be uncovered.ResultsWe generated a high-quality de novo Reference transcriptome for the annelid Platynereis dumerilii. We produced and analyzed three RNA-sequencing datasets, encompassing five stages of posterior regeneration, along with blastema stages and non-amputated tissues as controls. We included two of these regeneration RNA-seq datasets, as well as embryonic and tissue-specific datasets from the literature to produce a Reference transcriptome. We used this Reference transcriptome to perform in depth analyzes of RNA-seq data during the course of regeneration to reveal the important dynamics of the gene expression, process with thousands of genes differentially expressed between stages, as well as unique and specific gene expression at each regeneration stage. The study of these genes highlighted the importance of the nervous system at both early and late stages of regeneration, as well as the enrichment of RNA-binding proteins (RBPs) during almost the entire regeneration process.ConclusionsIn this study, we provided a high-quality de novo Reference transcriptome for the annelid Platynereis that is useful for investigating various developmental processes, including regeneration. Our extensive stage-specific transcriptional analysis during the course of posterior regeneration sheds light upon major molecular mechanisms and pathways, and will foster many specific studies in the future.

Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration

After traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding gene legumain. Analysis of legumain mutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration.

Gelatin Sponges with a Uniform Interoperable Pore Structure and Biodegradability for Liver Injury Hemostasis and Tissue Regeneration.

Developing a hemostatic sponge that can effectively control bleeding from visceral injuries while guiding in situ tissue regeneration in incompressible wounds remains a challenge. Most of the existing hemostatic sponges degrade slowly, are relatively single-functioning, and cannot cope with complex environments. Herein, a biodegradable rapidly hemostatic sponge (GPZ) was created by dual-dynamic-bond cross-linking among Zn2+, protocatechualdehyde (PA)-containing catechol and aldehyde groups, and gelatin. GPZ had a uniformly distributed interconnected pore structure with excellent fluid absorption. It could effectively absorb the oozing blood and increase the blood concentration while stimulating platelet activation and accelerating blood coagulation. Compared to commercial hemostats, GPZ treatment significantly accelerated hemostasis in the rat liver defect model (∼0.33 min, ≥50% reduction in the hemostatic time) and in the rabbit liver defect model (∼1.02 min, ≥60% reduction in the hemostatic time). Additionally, GPZ had excellent antibacterial and antioxidant properties that effectively protected the wound from infection and excessive inflammation. In the liver regeneration model, GPZ significantly increased the rate of hepatic tissue repair and promoted rapid functional recovery without complications and adverse reactions. Overall, we designed a simple and effective biodegradable rapid hemostatic sponge with good clinical translational potential for treating lethal incompressible bleeding and promoting wound healing.