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Abstract Salamanders possess remarkable regenerative capacities for organ regeneration among tetrapod vertebrates. Previous research has primarily focused on studying the regeneration of canonical tissues or organs such as limbs, tail, brain, spinal cord, heart, and lens. The advancements made in these areas have broader implications for understanding regeneration and developing therapeutic approaches for these organs, not only in salamanders but also in other vertebrates. In recent years, there has been an increasing interest in studying the regeneration of non‐canonical organs in salamanders, such as the liver, lungs, kidneys, and pancreas. This diversification of research has opened up new avenues and provided potential solutions to challenging clinical problems. This review aims to summarize the progress made in the field of non‐canonical organ regeneration in salamanders and provides an outlook on future research directions.

Abstract Background While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor‐5 (GDF‐5), no results have been publicly released. Aims The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF‐5 (0.25, 1, and 2 mg) as a therapeutic for disc regeneration. Materials and methods Firstly, this work experimentally determined the effects of GDF‐5 concentration on the metabolic and matrix synthesis rates of human nucleus pulposus (NP) cells. Secondly, in silico modeling was employed to predict the subsequent regenerative effect of different GDF‐5 treatments (± cells). Results This study suggests a trend of increased matrix synthesis with 0.25 and 1 mg of GDF‐5. However, 2 mg of GDF‐5 significantly upregulates oxygen consumption. Despite this, in silico models highlight the potential of growth factors in promoting matrix synthesis compared to cell‐only treatments, without significantly perturbing the nutrient microenvironment. Discussion This work elucidates the potential of GDF‐5 on human NP cells. Although the results did not reveal statistical differences across all doses, the variability and response among donors is an interesting finding. It highlights the complexity of human response to biological treatments and reinforces the need for further human research and personalized approaches. Furthermore, this study raises a crucial question about whether these potential biologics are more regenerative in nature or better suited as prophylactic therapies for younger patient groups. Conclusion Biological agents exhibit unique characteristics and features, demanding tailored development strategies and individualized assessments rather than a one‐size‐fits‐all approach. Therefore, the journey to realizing the full potential of biological therapies is long and costly. Nonetheless, it holds the promise of revolutionizing spinal healthcare and improving the quality of life for patients suffering from discogenic back pain.

Abstract The conversion of urban montane forest resources into urban parks requires careful assessment to understand its impacts on plant diversity over time. This study aims to enhance urban biodiversity conservation strategies by analyzing how habitat type and park age affect woody plant diversity. We surveyed woody plant species in 60 sample plots across two different habitats (remnant forest vs. artificial green space) within three mountain parks in Guiyang, China, established at different times. The alpha diversity of saplings/seedlings was significantly higher in remnant forests than in artificial green spaces. Artificial green spaces exhibited more homogenous woody plant composition compared with remnant forests. Newer parks showed greater variation in plant composition between the two habitats than older parks. Indicative species in remnant forests were predominantly native, whereas those in artificial green spaces were mainly ornamental species. The transformation of karst mountainous forests into urban parks leads to the homogenization of woody plant composition and impedes the regeneration of saplings/seedlings. Therefore, it is crucial to manage these conversions carefully and strive to preserve as many native species as possible to support urban plant diversity conservation.

Abstract Bioengineering and drug delivery technologies play an important role in bridging the gap between basic scientific discovery and clinical application of therapeutics. To identify the optimal treatment, the most critical stage is to diagnose the problem. Often these two may occur simultaneously or in parallel, but in this review, we focus on bottom‐up approaches in understanding basic immunologic phenomena to develop targeted therapeutics. This can be observed in several fields; here, we will focus on one of the original immunotherapy targets—cancer—and one of the more recent targets—regenerative medicine. By understanding how our immune system responds in processes such as malignancies, wound healing, and medical device implantation, we can isolate therapeutic targets for pharmacologic and bioengineered interventions.

Abstract Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM‐MSC), human immortalized MSC (hTERT‐MSC), human embryonic stem cells (ESC), ESC‐derived cardiac progenitor cells (CPC), human ESC‐derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC‐derived sEV (ESC‐sEV) exhibited the best pro‐angiogenic and anti‐fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI‐reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC‐sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down‐regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT‐MSC, ESC, and CPC revealed factors in ESC‐sEV that potentially drove the observed functions. In conclusion, ESC‐sEV holds great promise as a cell‐free treatment for promoting cardiac repair following MI.

Abstract Background The increasing interest in platelet‐based therapies has underwritten the development of novel veterinary regenerative treatments. The haemoderivative platelet‐rich fibrin (PRF) comprises abundant concentrations of platelets and leucocytes, above the physiologic baseline, which are considered essential elements for wound regeneration, stimulating local angiogenesis, cellular migration, proliferation and differentiation, considered essential for skin repair. Objectives This study aimed to describe the treatment of eight dogs with naturally occurring cutaneous wounds, where autologous PRF therapy was applied, using a protocol developed by our group. Methods Eight dogs, aged between 7‐month and 9‐year old, from different breeds and sexes, were enrolled in this study. Four of these wounds were clinically infected. In three cases, two PRF treatments were performed during the first week of treatment, followed by single weekly treatments from the second week onwards, until exophytic granulation tissues were present. In each case, the treatment was finalized only when complete wound closure was achieved. Wounds did not receive topical antiseptics, antibiotics or topical drugs to promote wound healing during the treatment. Results PRF‐grafting treatments were well tolerated in all treated wounds, inducing significant granulation tissue formation. PRF clots acted as a natural tissue filler, promoting epithelization and wound closure, without the requirement of topical antimicrobial/antiseptics application, or additional surgical debridement. Evident skin contraction was recorded in larger injuries and all the treatments resulted in vestigial aesthetic scars where hair growth was also observed. Conclusions PRF‐therapy obtained promising results, as an alternative wound treatment, revealing a biological regenerative action, prompting the natural skin healing process.

Abstract Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia‐inducible factor one‐alpha (HIF‐1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self‐assembly of PEG‐DPCA conjugates. Pre‐treatment of mice with PEG‐DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)‐induced colitis. Surprisingly, a single subcutaneous dose of PEG‐DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA‐induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF‐1α and associated targets leading to an epithelial‐to‐mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand‐alone restorative treatment to combat active IBD is warranted.

Abstract The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of “seeding and harvest”, are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast‐to‐DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two‐pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

Abstract Due to the limited capacity of mammals to regenerate complex tissues, researchers have worked to understand the mechanisms of tissue regeneration in organisms that maintain that capacity. One example is the MRL/MpJ mouse strain with unique regenerative capacity in ear pinnae that is absent from other strains, such as the common C57BL/6 strain. The MRL/MpJ mouse has also been associated with an autoimmune phenotype even in the absence of the mutant Fas gene described in its parent strain MRL/lpr. Due to these findings, the differences between the responses of MRL/MpJ versus C57BL/6 strain are evaluated in volumetric muscle injury and subsequent material implantation. One salient feature of the MRL/MpJ response to injury is robust adipogenesis within the muscle. This is associated with a decrease in M2‐like polarization in response to biologically derived extracellular matrix scaffolds. In pro‐fibrotic materials, such as polyethylene, there are fewer foreign body giant cells in the MRL/MpJ mice. As there are reports of both positive and negative influences of adipose tissue and adipogenesis on wound healing, this model can provide an important lens to investigate the interplay between stem cells, adipose tissue, and immune responses in trauma and material implantation.

Abstract 3D bioprinting holds great promise for meeting the increasing need for transplantable tissues and organs. However, slow printing, interlayer mixing, and the extended exposure of cells to non‐physiological conditions in thick structures still hinder clinical applications. Here the DeepFreeze‐3D (DF‐3D) procedure and bioink for creating multilayered human‐scale tissue mimetics is presented for the first time. The bioink is tailored to support stem cell viability, throughout the rapid freeform DF‐3D biofabrication process. While the printer nozzle is warmed to room temperature, each layer solidifies at contact with the stage (‐80 °C), or the subsequent layers, ensuring precise separation. After thawing, the encapsulated stem cells remain viable without interlayer mixing or delamination. The composed cell‐laden constructs can be cryogenically stored and thawed when needed. Moreover, it is shown that under inductive conditions the stem cells differentiate into bone‐like cells and grow for months after thawing, to form large tissue‐mimetics in the scale of centimeters. This is important, as this approach allows the generation and storage of tissue mimetics in the size and thickness of human tissues. Therefore, DF‐3D biofabrication opens new avenues for generating off‐the‐shelf human tissue analogs. It further holds the potential for regenerative treatments and for studying tissue pathologies caused by disease, tumor, or trauma.

Objective When the endoscopic Achilles tendon repair technique is utilized, direct stitching of the ruptured site is challenging due to the frayed tendon stumps. To explore whether undesirable coaptation of the tendon stumps influences the generation of the tendons. Methods This study is a retrospective analysis of 46 patients who underwent a modified endoscopic Achilles tendon rupture repair from October 2018 to June 2020. Patients were divided into two groups according to the coaptation of tendon stumps on postoperative ultrasonography. Group 1 included 17 cases with undesirable coaptation (

Abstract Background Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet‐to‐be‐fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho‐associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown. Methods Three‐dimensionally engineered dystrophin‐deficient mdx skeletal muscles and mdx mice were used to test the role of ROCK in DMD muscle function in vitro and in situ, respectively. The role of ARHGEF3, one of the RhoA guanine nucleotide exchange factors (GEFs), in RhoA/ROCK signalling and DMD pathology was examined by generating Arhgef3 knockout mdx mice. The role of RhoA/ROCK signalling in mediating the function of ARHGEF3 was determined by evaluating the effects of wild‐type or GEF‐inactive ARHGEF3 overexpression with ROCK inhibitor treatment. To gain more mechanistic insights, autophagy flux and the role of autophagy were assessed in various conditions with chloroquine. Results Inhibition of ROCK with Y‐27632 improved muscle force production in 3D‐engineered mdx muscles (+25% from three independent experiments, P

Abstract Somatic embryogenesis (SE) is a process by which an embryo is derived from somatic tissue. Transcription factors (TFs) have been identified that control this process. One such TF that promotes SE is AGAMOUS‐like 15 (AGL15). Prior work has shown that AGL15 can both induce and repress gene expression. One way this type of dual function TF works is via protein interactions, so a yeast 2‐hybrid (Y2H) screen was undertaken. One intriguing protein with which AGL15 interacted in Y2H was LBD40. LBD40 encodes a LATERAL ORGAN BOUNDARIES (LOB)‐domain TF that is unique to plants and is primarily expressed during seed development. Here, we confirm the AGL15‐LBD40 interaction by quantitative assays and in planta co‐immunoprecipation. We also document a role for LBD40, and the closely related protein LBD41, in supporting SE. To determine downstream genes potentially controlled by LBD40, chromatin immunoprecipitation followed by high throughput sequencing (ChIP‐seq) was used. More than 400 binding regions for LBD40 were consistently found genome‐wide. To determine genes responsive to LBD40/41 accumulation, RNA‐seq analysis of transcriptomes of wild‐type control and loss‐of‐function lbd40/lbd41 was performed. Combining these datasets provides insight into genes directly and indirectly controlled by these LOB domain TFs. The gene ontology (GO) enrichment analysis of these regulated genes showed an overrepresentation of biological processes that are associated with SE, further indicating the importance of LBD40 in SE. This work provides insight into SE, a poorly understood, but essential process to generate transgenic plants to meet agricultural demands or test gene function. This manuscript reports on experiments to understand the role that LDB40, a TF, plays in support of SE by investigating genes directly and indirectly controlled by LBD40 and examining physical and genetic interactions with other TFs active in SE. We uncover targets of LBD40 and an interacting TF of the MADS family and investigate targets involvement in SE.

Abstract Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin‐derived Fb. Although both soluble and cell‐surface factors contributed evenly to the neurite‐promoting effect of nerve‐derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.

Abstract Background Injection of exogenous mitochondria has been shown to improve the ischaemia‐damaged myocardium, but the effect of mitochondrial transplant therapy (MTT) to restore skeletal muscle mass and function has not been tested following neuromuscular injury. Therefore, we tested the hypothesis that MTT would improve the restoration of muscle function after injury. Methods BaCl2 was injected into the gastrocnemius muscle of one limb of 8–12‐week‐old C57BL/6 mice to induce damage without injury to the resident stem cells. The contralateral gastrocnemius muscle was injected with phosphate‐buffered saline (PBS) and served as the non‐injured intra‐animal control. Mitochondria were isolated from donor mice. Donor mitochondria were suspended in PBS or PBS without mitochondria (sham treatment) and injected into the tail vein of BaCl2 injured mice 24 h after the initial injury. Muscle repair was examined 7, 14 and 21 days after injury. Results MTT did not increase systemic inflammation in mice. Muscle mass 7 days following injury was 21.9 ± 2.1% and 17.4 ± 1.9% lower (P

Abstract Background A significant hurdle for potential cell‐based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell‐based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy. Aims This work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential. Materials and Methods First, this work experimentally investigated species‐specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species‐specific nutrient microenvironments and predict differences in temporal regeneration between animal models. Results This work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche. Discussion Overall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the “time to regeneration” between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell‐based regeneration. Conclusion Ultimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient‐specific models could be used for patient assessment, as well as pre‐ and intraoperative planning.

Abstract Regeneration of lost appendages is a gradual process in many species, spreading energetic costs of regeneration through time. Energy allocated to the regeneration of lost appendages cannot be used for other purposes and, therefore, commonly elicits energetic trade‐offs in biological processes. We used limb loss in the Asian shore crab Hemigrapsus sanguineus to compare the strength of energetic trade‐offs resulting from historic limb losses that have been partially regenerated versus current injuries that have not yet been repaired. Consistent with previous studies, we show that limb loss and regeneration results in trade‐offs that reduce reproduction, energy storage, and growth. As may be expected, we show that trade‐offs in these metrics from historic limb losses far outweigh trade‐offs from current limb losses, and correlate directly with the degree of historic limb loss that has been regenerated. As regenerating limbs get closer to their normal size, these historical injuries get harder to detect, despite the continued allocation of additional resources to limb development. Our results demonstrate the importance of and a method for identifying historic appendage losses and of quantifying the amount of regeneration that has already occurred, as opposed to assessing only current injury, to accurately assess the strength of energetic trade‐offs in animals recovering from nonlethal injury.

Abstract The Yes‐associated protein and its transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism‐related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ‐induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

Abstract Declining temperate forest biodiversity is a global challenge to future sustainability and resilience. Canopy tree diversity has declined in northern hardwood forests (NHFs) of the Great Lakes region since European colonization, with current tree regeneration patterns suggesting this trend may continue. However, regional (106 ha) patterns and drivers are underexplored. We used data from 141 managed NHF stands, Michigan, USA, to examine diversity indices across tree size classes (seedling, sapling, and canopy); stand‐level drivers of regeneration (seedling and sapling) diversity and individual species density; and patterns among species in relative abundances across size classes. Diversity was similar across size classes (mean asymptotic species richness of 6–7 species and 10% of sites were consistent with species life history strategy and/or establishment/recruitment barriers. For seven species (including Tsuga canadensis, Betula alleghaniensis), relative density was lowest in the seedling layer, suggesting seedling establishment substrate and/or early shade mortality limitations. For two species (Acer saccharum, Quercus rubra), reduced sapling relative density compared with seedling or canopy strata suggests a sapling recruitment bottleneck from deer browsing/shade, whereas six species (e.g., F. grandifolia, O. virginiana, Pinus strobus) had highest relative density for saplings, suggesting sapling to canopy recruitment limitations. Lastly, seedlings were relatively most dense for Acer rubrum and Prunus spp., indicating disproportionally high seedling establishment, if not sapling or canopy recruitment, and for F. americana, consistent with recent pest‐related canopy mortality. Collectively our analyses suggest sustained low diversity and shifting composition are driven by limited local seed availability, limited seedling establishment substrate, deep shading, and abundant deer. Management aimed at overcoming these limitations may be necessary to promote future NHF resilience.

Abstract Larix cajanderi forests, which occupy vast regions of Siberia, grow atop and protect carbon‐rich permafrost. Regeneration of these forests has important implications for long‐term feedbacks into the climate system and their regeneration is strongest following stand‐replacing fires. The goal of this project was to assess sources of regeneration limitation in L. cajanderi forests in northeastern Siberia. We focused on (1) regeneration potential of stands varying in tree density and (2) analyzing seedling establishment patterns in relationship to microsite conditions (safe sites) in the landscape. Seed sources were assessed through cone counts and stand surveys in the summers of 2017 and 2018 in 17 mature L. cajanderi stands. L. cajanderi recruitment patterns in relationship to safe site availability were assessed in 15 areas, spanning approximately 800 km2 along the northern portion of the Kolyma River (69.5477° N, 161.3641° E). Density of trees in a stand was negatively related to the number of cones that the average tree produced and stands of moderate density produced more cones per area than either high‐ or low‐density stands. L. cajanderi seedling establishment was facilitated by safe sites in the landscape. We discovered strong evidence that safe sites are considerably more important for seedling establishment in lowland sites than upland areas. The biological explanation for this pattern is presently unknown; however, we hypothesize this pattern is driven by persistently wet (marshy) soils in some lowland sites as a limiter of seedling establishment. Overall, these data suggest the potential for complex linkages between forest density, propagule availability, fire, safe sight colonization, and seedling establishment that may regulate long‐term dynamics in the understudied L. cajanderi forests of the Siberian Arctic.

Abstract Ammonia borane (AB), a liquid hydrogen storage material, has attracted increasing attention for hydrogen utilization because of its high hydrogen content. However, the slow kinetics of AB hydrolysis and the indefinite catalytic mechanism remain significant problems for its large‐scale practical application. Thus, the development of efficient AB hydrolysis catalysts and the determination of their catalytic mechanisms are significant and urgent. A summary of the preparation process and structural characteristics of various supported catalysts is presented in this paper, including graphite, metal‐organic frameworks (MOFs), metal oxides, carbon nitride (CN), molybdenum carbide (MoC), carbon nanotubes (CNTs), boron nitride (h‐BN), zeolites, carbon dots (CDs), and metal carbide and nitride (MXene). In addition, the relationship between the electronic structure and catalytic performance is discussed to ascertain the actual active sites in the catalytic process. The mechanism of AB hydrolysis catalysis is systematically discussed, and possible catalytic paths are summarized to provide theoretical considerations for the designing of efficient AB hydrolysis catalysts. Furthermore, three methods for stimulating AB from dehydrogenation by‐products and the design of possible hydrogen product‐regeneration systems are summarized. Finally, the remaining challenges and future research directions for the effective development of AB catalysts are discussed.

Abstract Compromised regeneration resulting from the deactivation of Wnt/β‐catenin signaling contributes to the progression of chronic obstructive pulmonary disease (COPD) with limited therapeutic options. Extracellular cytokine‐induced Wnt‐based signaling provides an alternative option for COPD treatment. However, the hydrophobic nature of Wnt proteins limits their purification and use. This study devises a strategy to deliver the membrane‐bound wingless‐type MMTV integration site family, member 3A (Wnt3a) over a long distance by anchoring it to the surface of extracellular vesicles (EVs). The newly engineered Wnt3aWG EVs are generated by co‐expressing Wnt3a with two genes encoding the membrane protein, WLS, and an engineered glypican, GPC6ΔGPI‐C1C2. The bioactivity of Wnt3aWG EVs is validated using a TOPFlash assay and a mesoderm differentiation model of human pluripotent stem cells. Wnt3aWG EVs activate Wnt signaling and promote cell growth following human alveolar epithelial cell injury. In an elastase‐induced emphysema model, impaired pulmonary function and enlarged airspace are greatly restored by the intravenous delivery of Wnt3aWG EVs. Single‐cell RNA sequencing–based analyses further highlight that Wnt3aWG EV‐activated regenerative programs are responsible for its beneficial effects. These findings suggest that EV‐based Wnt3a delivery represents a novel therapeutic strategy for lung repair and regeneration after injury.

Abstract It is challenging to efficiently and economically recycle many lithium‐ion batteries (LIBs) because of the low valuation of commodity metals and materials, such as LiFePO4. There are millions of tons of spent LIBs where the barrier to recycling is economical, and to make recycling more feasible, it is required that the value of the processed recycled material exceeds the value of raw commodity materials. The presented research illustrates improved profitability and economics for recycling spent LIBs by utilizing the surplus energy in lithiated graphite to drive the preparation of organolithiums to add value to the recycled lithium materials. This study methodology demonstrates that the surplus energy of lithiated graphite obtained from spent LIBs can be utilized to prepare high‐value organolithiums, thereby significantly improving the economic profitability of LIB recycling. Organolithiums (R–O–Li and R–Li) were prepared using alkyl alcohol (R–OH) and alkyl bromide (R–Br) as substrates, where R includes varying hindered alkyl hydrocarbons. The organolithiums extracted from per kilogram of recycled LIBs can increase the economic value between $29.5 and $226.5 kg−1 cell. The value of the organolithiums is at least 5.4 times the total theoretical value of spent materials, improving the profitability of recycling LIBs over traditional pyrometallurgical ($0.86 kg−1 cell), hydrometallurgical ($1.00 kg−1 cell), and physical direct recycling methods ($5.40 kg−1 cell).

Abstract The monitoring of tissue regeneration is particularly important. However, most materials do not allow direct observation of the regeneration process in the cartilage layer. Here, using sulfhydryl polyhedral oligomeric silsesquioxane (POSS‐SH) as a nano‐construction platform, poly(ethylene glycol) (PEG), Kartogenin (KGN), hydrogenated soya phosphatidylcholine (HSPC), and fluorescein are linked through the “click chemistry” method to construct nanomaterial with fluorescence visualization for cartilage repair: POSS linked with PEG, KGN, HSPC, and fluorescein (PPKHF). PPKHF nanoparticles are encapsulated with hyaluronic acid methacryloyl to prepare PPKHF‐loaded microfluidic hyaluronic acid methacrylate spheres (MHS@PPKHF) for in situ injection into the joint cavity using microfluidic technology. MHS@PPKHF forms a buffer lubricant layer in the joint space to reduce friction between articular cartilages, while releasing encapsulated positively charged PPKHF to the deep cartilage through electromagnetic force, facilitating visualization of the location of the drug via fluorescence. Moreover, PPKHF facilitates differentiation of bone marrow mesenchymal stem cells into chondrocytes, which are located in the subchondral bone. In animal experiment, the material accelerates cartilage regeneration while allowing monitoring of cartilage layer repair progression via fluorescence signals. Thus, these POSS‐based micro–nano hydrogel microspheres can be used for cartilage regeneration and monitoring and potentially for clinical osteoarthritis therapy.

Abstract Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Its biological functions include metabolic stress adaptation, stem cell differentiation, immunomodulation and diseases regulation, and so on. Current researches have proved that autophagy dysfunction may contribute to the pathogenesis of some myopathies through impairment of myofibres regeneration. Studies of autophagy inhibition also indicate the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. In this review, we aim to report the mechanisms of action of autophagy on muscle regeneration to provide relevant references for the treatment of regenerating defective myopathies by regulating autophagy. Results have shown that one key mechanism of autophagy regulating the muscle regeneration is to affect the differentiation fate of muscle stem cells (MuSCs), including quiescence maintenance, activation and differentiation. The roles of autophagy (organelle/protein degradation, energy facilitation, and/or other) vary at different myogenic stages of the repair process. When the muscle is in homeostasis, basal autophagy can maintain the quiescence state and stemness of MuSCs by renewing organelle and protein. After injury, the increased autophagy flux contributes to meet biological energy demand of MuSCs during activation and proliferation. By mitochondrial remodelling, autophagy during differentiation can promote the metabolic transformation and balance mitochondrial‐mediated apoptosis signals in myoblasts. Autophagy in mature myofibres is also essential for the degradation of necrotic myofibres, and may affect the dynamics of MuSCs by affecting the secretion spectrum of myofibres or the recruitment of supporting cells. Except for myogenic cells, autophagy also plays an important role in regulating the function of non‐myogenic cells in the muscle microenvironment, which is also essential for successful muscle recovery. Autophagy can regulate the immune microenvironment during muscle regeneration through the recruitment and polarization of macrophages, while autophagy in endothelial cells can regulate muscle regeneration in an angiogenic or angiogenesis‐independent manner. Drug or nutrition targeted autophagy has been preliminarily proved to restore muscle function in myopathies by promoting muscle regeneration, and further understanding the role and mechanism of autophagy in various cell types during muscle regeneration will enable more effective combinatorial therapeutic strategies.

Acute liver injury is a serious clinical syndrome with multiple causes and unclear pathological process. Here, CCl4‐ and D‐galactosamine/lipopolysaccharide (D‐gal/LPS)‐induced acute liver injury was established to explore the cell death patterns and determine whether or not liver regeneration occurred. In CCl4‐induced hepatic injury, three phases, including the early, progressive, and recovery phase, were considered based on alterations of serum transaminases and liver morphology. Moreover, in this model, cytokines exhibited double‐peak fluctuations; apoptosis and pyroptosis persisted throughout all phases; autophagy occurred in the early and the progressive phases; and sufficient and timely hepatocyte regeneration was observed only during the recovery phase. All of these phenomena contribute to mild liver injury and subsequent regeneration. Strikingly, only the early and progressive phases were observed in the D‐gal/LPS model. Slight pyroptosis occurred in the early phase but diminished in the progressive phase, while apoptosis, reduced autophagy, and slight but subsequently diminished regeneration occurred only during the progressive phase, accompanied by a strong cytokine storm, resulting in severe liver injury with high mortality. Taken together, our work reveals variable modes and dynamics of cell death and regeneration, which lead to different consequences for mild and severe acute liver injury, providing a helpful reference for clinical therapy and prognosis.

Key Clinical Message Regenerative endodontics holds promising potential for the regeneration of living tissues in teeth with necrotic pulp and periapical lesion. Platelet‐rich plasma can be easily prepared and used as an ideal scaffold for pulp regeneration.

Abstract There is growing production for lithium‐ion batteries (LIBs) to satisfy the booming development renewable energy storage systems. Meanwhile, amounts of spent LIBs have been generated and will become more soon. Therefore, the proper disposal of these spent LIBs is of significant importance. Graphite is the dominant anode in most commercial LIBs. This review specifically focuses on the recent advances in the recycling of graphite anode (GA) from spent LIBs. It covers the significance of GA recycling from spent LIBs, the introduction of the GA aging mechanisms in LIBs, the summary of the developed GA recovery strategies, and the highlight of reclaimed GA for potential applications. In addition, the prospect related to the future challenges of GA recycling is given at the end. It is expected that this review will provide practical guidance for researchers engaged in the field of spent LIBs recycling.

Abstract Effective regeneration of adsorbents is considered as one of the essential qualities for commercial use. However, most of the studies have only reported the adsorption properties and overlooked the reuse of adsorbents. In this study, we determined the regenerability and reusability of fly‐ash derived zeolite (FADZ) NaP1. These adsorbents have become popular to remove pollutants from water, including toxic metals, since they are less expensive, compared to their counterparts, and can be synthesized from a waste product. We evaluated the efficiency of copper (Cu2+) ions recovery from water using multiple regeneration solutions due to medium adsorption selectivity towards Cu2+. We determined the time required for the regeneration using acid, base, and salt solutions. The suitable pH and solution while maintaining the structure of the zeolite were studied. Up to 90% recovery was achieved via three successive regenerations, each taking 3 h using 3 M KCl and 3 M NaCl solutions. X‐ray diffraction (XRD) and fluorescence showed changes in structure after regeneration at pH

Abstract Background Quadriceps tendon ruptures (QTRs) are rare but debilitating injuries, often associated with chronic metabolic conditions or long‐term steroid treatment. While the surgical treatment for acute QTRs is described thoroughly, no common strategy exists for the often frustrating treatment of chronic, reoccurring QTRs. The pro‐angiogenic and immunomodulatory properties of placenta‐derived adherent mesenchymal stromal‐like (PLX‐PAD) cells have been described to protect musculoskeletal tissues from inflammation and catabolic cytokine migration, yet little is known about the regenerative potential of PLX‐PAD cells in repetitively damaged tendon tissue. Case We report the case of an 80‐year‐old male patient with a chronic three‐time QTR of his right knee. The quadriceps tendon was reconstructed applying a conventional suture anchor repair procedure combined with a synthetic mesh augmentation and additional intramuscular and intratendineous PLX‐PAD cell injections as an individualized treatment approach. No adverse events were reported, and excellent radiological and functional outcomes with a passive range of motion of 0/0/120° knee extension‐flexion were observed at the 12 month follow‐up. Gait analysis confirmed restoration of joint motion, including gait speed, deficit in step length, and knee extensor muscle strength (pre‐surgery: 0.98 m/s, 40 cm, 42.4 ± 12.4 N; 9 months post‐surgery: 1.07 m/s, 0 cm, 10.4 ± 18.9 N) as well as hyperextension throughout stance and late swing phases (pre‐surgery: −11.2 ± 0.9°; 9 months post‐surgery: −2.7 ± 1.6°). Postoperative lymphocyte and cytokine analyses from the patient's peripheral blood serum suggested a systemic short‐term immunoregulatory reaction with postoperatively increased interleukin (IL)‐6 (pre‐surgery: 0.79 pg/mL; day 1: 139.97 pg/mL; day 5: 5.58 pg/mL; 9 months: 1.76 pg/mL) and IL‐10 (pre‐surgery: 0.9 pg/mL; day 1: 1.21 pg/ mL; day 5: 0.3 pg/mL; 9 months: 0.34 pg/mL) levels that decreased again over time. Conclusions Herein, we demonstrate a successfully treated chronic QTR with a synergistic surgical and biological reconstructive treatment approach. This local add‐on treatment with PLX‐PAD cells may be considered in specific cases of chronic QTRs, not susceptible to traditional suture anchor procedures and which exhibit a high risk of treatment failure. Further scientific engagement is warranted to explore underlying immunomodulatory mechanisms of action behind PLX‐PAD cell treatment for tendon injuries.

Abstract Background Circular RNAs (circRNAs) represent a novel class of non‐coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown. Methods Strand‐specific RNA‐sequencing (RNA‐seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single‐cell RNA‐seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration in vitro or in vivo by RT‐qPCR, western blotting, dual‐luciferase activity assay, RNA immunoprecipitation, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation. Results We profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52 918 high‐confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log2 fold change| > 1 and adjusted P value

Abstract Background As paediatric cancer survivors are living into adulthood, they suffer from the age‐related, accelerated decline of functional skeletal muscle tissue, termed sarcopenia. With ionizing radiation (radiotherapy) at the core of paediatric cancer therapies, its direct and indirect effects can have lifelong negative impacts on paediatric growth and maintenance of skeletal muscle. Utilizing our recently developed preclinical rhabdomyosarcoma mouse model, we investigated the late effects of paediatric radiation treatment on skeletal muscles from late adolescent (8 weeks old) and middle‐aged (16 months old) mice. Methods Paediatric C57BL/6J male mice (3 weeks old) were injected with rhabdomyosarcoma cells into their right hindlimbs, and then fractionated irradiation (3 × 8.2 Gy) was administered to those limbs at 4 weeks old to eliminate the tumours. Radiation‐alone and tumour‐irradiated mice were assessed at either 8 weeks (3 weeks post‐irradiation) or 16 months (14 months post‐irradiation) of age for muscle physiology, myofibre characteristics, cell loss, histopathology, fibrosis, inflammatory gene expression, and fibrotic gene expression. Results Mice that received only paediatric radiation demonstrated reduced muscle mass (−17%, P

Abstract Objectives To investigate if the application of the granulation tissue preservation technique (GTPT) in regenerative therapy of infrabony periodontal defects results in more clinical attachment level (CAL) gain and more radiographic bone gain (RBG) than the conventional resective approach 12 months after surgery. Materials and methods Forty patients exhibiting at least one infrabony defect with a probing pocket depth (PPD) ≥6 mm and a radiographic infrabony component (INFRAX‐ray) ≥3 mm were randomly treated with the GTPT (test group) or the double‐flap approach with resection of the defect‐filling granulation tissue (control group). Enamel matrix derivatives were applied in both groups. Clinical and radiographic parameters were recorded at baseline (t0), 6 months (t1), and 12 months (t2) after surgery. The primary outcome variable was CAL gain between t0 and t2. Results When all patients were considered, ΔCALt0–t2 did not differ significantly between the two groups (p = .160). Significant PPD reduction (test group: 4.38 ± 1.36 mm; control group: 4.06 ± 2.38 mm), CAL gain (test group: 3.75 ± 1.24 mm; control group: 2.88 ± 2.09 mm), and RBG (test group: 3.06 ± 1.74 mm; control group: 3.27 ± 2.19 mm) were achieved at t2 in both groups. Using multivariate linear regression, PPDt0 and group were identified as variables with the greatest influence on ΔCALt0–t2. PPDt0 and INFRAX‐ray were identified as variables with the greatest influence on RBGt0–t2. Patients with a defect angle >22° showed significantly more CAL gain in the test group (t0–t1: 3.08 ± 1.38 mm; t0–t2: 3.62 ± 0.96 mm) than in the control group (t0–t1: 1.77 ± 1.54 mm; t0–t2: 2.18 ± 1.83 mm). Conclusions Regarding all patients, the study failed to show significant differences between the test and control groups. However, the GTPT appears to lead to more CAL gain in noncontaining infrabony defects.

Abstract Nerve dependence in regeneration has been established more than 200 years ago but the mechanisms by which nerves are necessary to regeneration remain to be fully elucidated. Aside from their direct impact in stimulating cellular growth, nerves also have a role on the establishment of body polarities (antero‐posterior and dorso‐ventral patterns) and this has been particularly well studied in nereid annelid worms. Nereids can regenerate appendages (parapodia) and the tail (body segments). In both parapodia and tail regeneration, the presence of the nerve cord is necessary to the establishment of body polarities. In this review, we will detail the experimental procedures which have been conducted in nereids to elucidate the role of the nerve cord in the establishment of the antero‐posterior and dorso‐ventral polarities. Most of the studies reported here were published several decades ago and based on anatomical and histological analyses; this review should constitute a knowledgebase and an inspiration for needed modern‐time explorations at the molecular levels to elucidate the impact of the nervous system in the acquisition of body polarities.

Abstract Abnormal endometrial receptivity is a major cause of the failure of embryo transplantation, which may lead to infertility, adverse pregnancy, and neonatal outcomes. While hormonal treatment has dramatically improved the fertility outcomes in women with endometriosis, a substantial unmet need persists in the treatment. In this study, methacrylate gelatin (GelMA) and methacrylate sericin (SerMA) hydrogel with human umbilical cord mesenchymal stem cells (HUMSC) encapsulation was designed for facilitating endometrial regeneration and fertility restoration through in situ injection. The presented GelMA/10%SerMA hydrogel showed appropriate swelling ratio, good mechanical properties, and degradation stability. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell encapsulation ability of HUMSC. Further in vivo experiments demonstrated that GelMA/SerMA@HUMSC hydrogel could increase the thickness of endometrium and improve the endometrial interstitial fibrosis. Moreover, regenerated endometrial tissue was more receptive to transfer embryos. Summary, we believed that GelMA/SerMA@HUMSC hydrogel will hold tremendous promise to repair or regenerate damaged endometrium.

Abstract Although the role of nerves in stimulating cellular growth and dissemination has long been described in tissue regeneration studies, until recently a similar trophic role of nerves in disease was not well recognized. However, recent studies in oncology have demonstrated that the growth and dissemination of cancers also requires the infiltration of nerves in the tumor microenvironment. Nerves generate various neurosignaling pathways, which orchestrate cancer initiation, progression, and metastases. Similarly, nerves are increasingly implicated for their regulatory functions in immunity and inflammation. This orchestrator role of nerves in cellular and molecular interactions during regeneration, cancer, immunity, and inflammation offers new possibilities for targeting or enhancing neurosignaling in human health and diseases.

Abstract Intervertebral disc (IVD) degeneration (IDD) is the main contributor to chronic low back pain. To date, the present therapies mainly focus on treating the symptoms caused by IDD rather than addressing the problem itself. For this reason, researchers have searched for a suitable biomaterial to repair and/or regenerate the IVD. A promising candidate to fill this gap is silk, which has already been used as a biomaterial for many years. Therefore, this review aims first to elaborate on the different origins from which silk is harvested, the individual composition, and the characteristics of each silk type. Another goal is to enlighten why silk is so suitable as a biomaterial, discuss its functionalization, and how it could be used for tissue engineering purposes. The second part of this review aims to provide an overview of preclinical studies using silk‐based biomaterials to repair the inner region of the IVD, the nucleus pulposus (NP), and the IVD's outer area, the annulus fibrosus (AF). Since the NP and the AF differ fundamentally in their structure, different therapeutic approaches are required. Consequently, silk‐containing hydrogels have been used mainly to repair the NP, and silk‐based scaffolds have been used for the AF. Although most preclinical studies have shown promising results in IVD‐related repair and regeneration, their clinical transition is yet to come.

Abstract The ever‐growing depletion of precious metals in modern electronic industry necessitates unremitting exploitation of novel materials for gold recovery from e‐waste. Herein, a freestanding poly(imine dioxime) (PIDO) membrane has been successfully fabricated for highly efficient recovery of gold from e‐waste. The consummate integration of abundant binding sites and hierarchically porous architecture renders the resulting PIDO membrane with a record‐breaking uptake capacity (9250 mg g−1) toward gold, fast adsorption equilibrium time, as well as satisfactory regeneration and reusability. Furthermore, PIDO membrane is also well competent for selective gold recovery from waste central processing unit leachate with remarkable efficiency (>99%). Considering high recovery efficiency, outstanding selectivity, and simple/scalable production process, the proposed PIDO membrane will hold huge prospect in the sustainable recovery of gold from e‐waste.

Earthworms are a highly abundant species in nature, with nearly 7000 different species being discovered. Despite the similarities in morphology among earthworm species, their regeneration capabilities vary based on the clitellum. The clitellum plays a crucial role in the clitellum-dependent worms, as it is involved in the processes of regeneration and reproduction in earthworms. The fascinating characteristic of the clitellum, which serves as a hub for stem cells in clitellum-dependent worms, plays a crucial role in various biological processes that require further exploration. This review focuses on the overall physiological functions and uncovers the lesser-known roles of the clitellum that have been documented in various research articles. In recent times, numerous studies have been conducted using the earthworm model to explore various areas. In that regard, the clitellum's different roles in regulating and controlling stem cells, the regeneration process, regulation of organogenesis, stress response, aging, autotomy, and various features have been briefly discussed. Ultimately, we emphasized the unique and versatile role of the clitellum in the animal model, making it an ideal choice for studying development, regeneration, stem cells, organogenesis, toxicology, autotomy, and aging response., (© 2024 American Association for Anatomy.)

Using immunocytochemistry, serotonergic nerve elements were documented in the nervous system of the planarian Girardia tigrina. Serotonin-immunopositive components were observed in the brain, ventral, dorsal and longitudinal nerve cords, transverse nerve commissures connecting the nerve cords, and in the nerve plexus. Whole-mount preparations of G. tigrina were analyzed by fluorescent and confocal laser scanning microscopy. An essential quantitative morphometric measurement of serotonin-immunopositive structures was conducted in three body regions (anterior, middle, and posterior) of the planarian. The number of serotonin neurons was maximal in the head region. The ventral nerve cords gradually decreased in thickness from anterior to posterior body ends. Physiological action of exogenously applied serotonin was studied in G. tigrina for the first time. It was found that serotonin (0.1 and 1 µmol L -1 ) accelerated eye regeneration. The transcriptome sequencing performed for the first time for the planarian G. tigrina revealed the transcripts of the tryptophan hydroxylase (trph), amino acid decarboxylase (aadc) and serotonin transporter (sert) genes. The data obtained indicate the presence of the components of serotonin pathway in G. tigrina. The identified transcripts can take part in serotonin turnover and participate in the realization of biological effects of serotonin in planarians, associated with eyes regeneration and differentiation., (© 2024 Wiley Periodicals LLC.)

Abstract There is increasing momentum to implement conservation and management approaches that adapt forests to climate change so as to sustain ecosystem functions. These range from actions designed to increase the resistance of current composition and structure to negative impacts to those designed to transition forests to substantially different characteristics. A component of many adaptation approaches will likely include assisted migration of future climate‐adapted tree species or genotypes. While forest‐assisted migration (FAM) has been discussed conceptually and examined experimentally for almost a decade, operationalizing FAM (i.e., routine use in forest conservation and management projects) lags behind the acceptance of the need for climate adaptation. As the vulnerability of forest ecosystems in climate change increases, FAM may need to become an integral management tool to reduce long‐term risks to ecosystem function, despite real and perceived barriers for its implementation. Here we discuss the concept of operational‐scale FAM and why it remains a controversial, not yet widely adopted component of climate adaptation. We present three case studies of operational‐scale FAM to illustrate how the practice can be approached pragmatically within an adaptation framework despite the barriers to acceptance. Finally, we discuss a path toward advancing the wide use of operational‐scale FAM.

Abstract Background Repopulating the degenerated intervertebral disc (IVD) with tissue‐specific nucleus pulposus cells (NPCs) has already been shown to promote regeneration in various species. Yet the applicability of NPCs as cell‐based therapy has been hampered by the low cell numbers that can be extracted from donor IVDs and their potentially limited regenerative capacity due to their degenerated phenotype. To optimize the expansion conditions, we investigated the effects of increasing culture medium osmolarity during expansion on the phenotype of dog NPCs and their ability to produce a healthy extracellular matrix (ECM) in a 3D culture model. Methods Dog NPCs were expanded in expansion medium with a standard osmolarity of 300 mOsm/L or adjusted to 400 or 500 mOsm/L in both normoxic and hypoxic conditions. Following expansion, NPCs were cultured in a 3D culture model in chondrogenic culture medium with a standard osmolarity. Read‐out parameters included cell proliferaton rate, morphology, phenotype and healthy ECM production. Results Increasing the expansion medium osmolarity from 300 to 500 mOsm/L resulted in NPCs with a more rounded morphology and a lower cell proliferation rate accompanied by the expression of several healthy NPC and progenitor markers at gene (KRT18, ACAN, COL2, CD73, CD90) and protein (ACAN, PAX1, CD24, TEK, CD73) level. The NPCs expanded at 500 mOsm/L were able to retain most of their phenotypic markers and produce healthy ECM during 3D culture independent of the oxygen level used during expansion. Conclusions Altogether, our findings show that increasing medium osmolarity during expansion results in an NPC population with improved phenotype, which could enhance the potential of cell‐based therapies for IVD regeneration.

Abstract Background Eccentric contractions induce muscle damage (EIMD) that compromises muscle function. Poor recovery from EIMD has been suggested to be a contributor to the decline in muscle function evident in sarcopenia, but it is unclear which aspects of muscle function are more susceptible to disruption by EIMD in old versus young muscle. The purpose of this study was to determine the extent of impairment in contractile function (force, fatigue, tetanus and twitch kinetics) during the recovery from EIMD in VO mice compared to young adult (YA). Methods Male CB6F1 were obtained from National Institure of Aging colony. VO mice were 29–31 months of age, and YA mice were 7–9 months of age. The plantarflexor muscles were subjected to 20 eccentric contractions in vivo to induce injury (EIMD). Changes in tetanic force and kinetics were assessed before EIMD, immediately after EIMD and 3 days after EIMD (3d‐EIMD). Force–frequency and rates of fatigue were assessed 3d‐EIMD and compared with baseline. Histological analysis was conducted in injured and non‐injured contralateral gastrocnemius muscle. Results There was a greater loss in isometric tetanic force immediately following EIMD in VO compared with YA (−31.6% ± 10.4 vs. −21.7% ± 6.0, P

Abstract Objectives Transplantation of stem cells into wounds has become popular in regeneration therapies. As stem cells for transplantation, human dental pulp stem cells (hDPSCs) are known to be pluripotent cells that are relatively easy to collect from the pulp of deciduous or wisdom teeth. The purpose of this study was to investigate whether hDPSCs treated with fibroblast growth factor 7 (FGF7) would contribute to the regeneration of wounded rat submandibular glands (SMGs). Materials and methods In in vitro studies, hDPSCs were treated with or without FGF7 and mRNA expression levels were examined at days 3, 7 and 14 using qRT‐PCR. The target genes analyzed were BMI1 as an undifferentiated marker, AQP5 as an acinar cell marker, CK19 as a ductal epithelial cell marker, αSMA as a myoepithelial cell marker and VIMENTIN as a fibroblast marker. In in vivo studies, hDPSCs treated with or without FGF7 for 14 days were mixed with type I collagen gels and were transplanted into wounded rat SMGs. Hematoxylin–Eosin and immunohistochemical staining were performed at days 3 and 7, and the numbers of positive cells were counted. The primary antibodies used were against BMI1, AQP5, αSMA, PanCK and VIMENTIN. Results In the in vitro studies, mRNA levels of BMI1 were decreased and αSMA were increased at days 3, 7 and 14, while AQP5 was increased at day 14 in the FGF7 group. In the in vivo studies, the proliferation of hDPSCs and cell islands was observed at day 7 in the FGF7 group. Few BMI1‐positive cells were observed, while numbers of AQP5‐positive and αSMA‐positive cells were increased at days 3 and 7 in the FGF7 group. Moreover, cell islands were AQP5‐positive. Conclusion These results suggest that FGF7‐treated hDPSCs differentiate into AQP5‐positive and αSMA‐positive cells. Moreover, AQP5‐positive cell aggregations were formed.

Abstract Lithium‐ion batteries (LIBs) are booming in multiple fields due to a rapid development in the last decade. However, limited by operational lifespans, a growing number of spent LIBs reaching the end of their lives are consequently faced with serious accumulation and descended to hazardous waste. Without proper disposal, the spent LIBs will inevitably cause negative influence on the ecology and undermine the sustainable manufacture of LIBs. The initial research of recycling strategies mainly focused on the optimization of metallurgical processes. Recently, the sustainability of the recycling process has attracted much more attention and become an important factor. Here, we summarize the recent progress of the spent LIBs recycling from a sustainable perspective, especially discussing the green innovations in recycling strategies for spent LIBs. Through this article, we expect to reveal the challenges and developing tendency of the recycling strategies and provide a guideline for future researches on processing spent LIBs and beyond, like the recycling of the solid‐state lithium metal batteries.

Abstract Despite a prevalence greater than cancer or diabetes, there are no currently approved drugs for the treatment of hearing loss. Research over the past two decades has led to a vastly improved understanding of the cellular and molecular mechanisms in the cochlea that lead to hearing deficits and the advent of novel strategies to combat them. Combined with innovative methods that enable local drug delivery to the inner ear, these insights have paved the way for promising therapies that are now under clinical investigation. In this review, we will outline this renaissance of cochlear biology and drug development, focusing on noise, age‐related, and chemotherapy‐induced hearing dysfunction.

Abstract This study was designed to investigate the regulatory effect of hyaluronic acid (HA)—coating silk fibroin (SF) nanofibers during epithelialization of urinary tract for urethral regeneration. The obtained electrospun biomimetic tubular HA‐SF nanofiber scaffold is composed of a dense inner layer and a porous outer layer in order to mimic adhesion and cavernous layers of the native tissue, respectively. A thin layer of HA‐gel coating was fixed in the inner wall to provide SF nanofibers with a dense and smooth surface nano‐topography and higher hydrophilicity. Compared with pure SF nanofibers, HA‐SF nanofibers significantly promoted the adhesion, growth, and proliferation of primary urothelial cells, and up‐regulate the expression of uroplakin‐3 (terminal differentiation keratin protein in urothelium). Using the New Zealand male rabbit urethral injury model, the scaffold composed of tubular HA‐SF nanofibers could recruit lumen and myoepithelial cells from the adjacent area of the host, rapidly reconstructing the urothelial barrier in the wound area in order to keep the urinary tract unobstructed, thereby promoting luminal epithelialization, smooth muscle bundle structural remodeling, and capillary formation. Overall, the synergistic effects of nano‐topography and biophysical cues in a biomimetic scaffold design for effective endogenous regeneration.

Abstract Introduction Mounting evidence suggest that macrophages play crucial roles in disease and tissue regeneration. However, despite much efforts during the past decade, our knowledge about the extent of macrophages' contribution to adult pancreatic regeneration after injury or during pancreatic disease progression is still limited. Nevertheless, it is generally accepted that some macrophage features that normally would contribute to healing and regeneration may be detrimental in pancreatic cancer. Altogether, the current literature contains conflicting reports on whether macrophages act as friends or foe in these conditions. Methods and Results In this review, we briefly review the origins of tissue resident and infiltrating macrophages and the importance of cellular crosstalking between macrophages and other resident cells in tissue regeneration. The primary objective of this review is to summarize our knowledge of the distinct roles of tissue resident and infiltrating macrophages, the impact of M1 and M2 macrophage phenotypes, and emerging evidence on macrophage crosstalking in pancreatic injury, regeneration, and disease. Conclusion Macrophages are involved with various stages of pancreatic cancer development, pancreatitis, and diabetes. Elucidating their role in these conditions will aid the development of targeted therapeutic treatments.

Abstract Arthroscopic saucerization of the lateral discoid meniscus is considered due to an increase in the load of the lateral compartment after high tibial osteotomy (HTO). We report a case of lateral discoid meniscus regeneration after arthroscopic saucerization in a middle‐aged female patient who underwent HTO.

Chronic rotator cuff (RC) injuries can lead to a degenerative microenvironment that favors chronic inflammation, fibrosis, and fatty infiltration. Recovery of muscle structure and function will ultimately require a complex network of muscle resident cells, including satellite cells, fibro-adipogenic progenitors (FAPs), and immune cells. Recent work suggests that signaling from adipose tissue and progenitors could modulate regeneration and recovery of function, particularly promyogenic signaling from brown or beige adipose (BAT). In this study, we sought to identify cellular targets of BAT signaling during muscle regeneration using a RC BAT transplantation mouse model. Cardiotoxin injured supraspinatus muscle had improved mass at 7 days postsurgery (dps) when transplanted with exogeneous BAT. Transcriptional analysis revealed transplanted BAT modulates FAP signaling early in regeneration likely via crosstalk with immune cells. However, this conferred no long-term benefit as muscle mass and function were not improved at 28 dps. To eliminate the confounding effects of endogenous BAT, we transplanted BAT in the "BAT-free" uncoupling protein-1 diphtheria toxin fragment A (UCP1-DTA) mouse and here found improved muscle contractile function, but not mass at 28 dps. Interestingly, the transplanted BAT increased fatty infiltration in all experimental groups, implying modulation of FAP adipogenesis during regeneration. Thus, we conclude that transplanted BAT modulates FAP signaling early in regeneration, but does not grant long-term benefits., (© 2024 Orthopaedic Research Society.)