Regeneration Process Research Articles

Hyperoxic-hypoxic Paradox: Breast Cancer Microenvironment and an Innovative Treatment Strategy.

A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells. Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.

Effect of M2-macrophage treated lymphatic endothelial cells on angiogenesis that promoted osteointegration

Early vascularization plays an essential role during the whole process in bone regeneration because of the function of secreting cytokines, transporting nutrients and metabolic wastes. As the preliminary basis of bone repair, angiogenesis is regulated by immune cells represented by macrophages to a great extent. However, with the discovery of the endolymphatic circulation system inside bone tissue, the role of vascularization became complicated and confusing. Herein, we developed a macrophage/ lymphatic endothelial cells (LECs)/ human umbilical vein endothelial cells (HUVECs) co-culture system to evaluate the effect of macrophage treated lymphatic endothelial cells on angiogenesis in vitro and in vivo. In this study, we collected the medium from macrophage (CM) for LECs culture. We found that CM2 could promote the expression of LECs markers and migration ability, which indicated the enhanced lymphogenesis. In addition, the medium from LECs was collected for culturing HUVECs. The CM2-treated LECs showed superior angiogenesis property including the migration capacity and expression of angiogenetic markers, which suggested the superior vascularization. Rat femoral condyle defect model was applied to confirm the hypothesis in vivo. Generally, M2-macrophage treated LECs showed prominent angiogenetic potential coupling with osteogenesis.

Can Microbiome Modulate Regenerative Capacity? A Comparative Microbiome Study Reveals a Dominant Presence of Flavobacteriaceae in Blastema Tissue During Axolotl Limb Regeneration.

The axolotl (Ambystoma mexicanum) is renowned for its remarkable regenerative capabilities, which are not diminished by the transition from a neotenic to a metamorphic state. This study explored the microbiome dynamics in axolotl limb regeneration by examining the microbial communities present in neotenic and metamorphic axolotls at two critical stages of limb regeneration: pre-amputation and during blastema formation. Utilizing 16S rRNA amplicon sequencing, we investigated the variations in microbiome profiles associated with different developmental and regenerative states. Our findings reveal a distinct separation in the microbiome profiles of neotenic and metamorphic samples, with a clear demarcation in microbial composition at both the phylum and genus levels. In neotenic 0DPA samples, Proteobacteria and Firmicutes were the most abundant, whereas in neotenic 7DPA samples, Proteobacteria and Bacteroidetes dominated. Conversely, metamorphic samples displayed a higher abundance of Firmicutes and Bacteroidetes at 0DPA and Proteobacteria and Firmicutes at 7DPA. Alpha and beta diversity analyses, along with dendrogram construction, demonstrated significant variations within and between the sample groups, suggesting a strong influence of both developmental stage and regenerative state on the microbiome. Notably, Flavobacterium and Undibacterium emerged as distinctive microbial entities in neotenic 7DPA samples, highlighting potential key players in the microbial ecology of regeneration. These findings suggest that the axolotl's microbiome is dynamically responsive to blastema formation, and they underscore the potential influence of microbial communities on the regeneration process. This study lays the groundwork for future research into the mechanisms by which the microbiome may modulate regenerative capacity.

Knockdown of miR-361-5p promotes the induced activation of SHF-stem cells through FOXM1 mediated Wnt/β-catenin pathway in cashmere goats

The inducing activation event of secondary hair follicle (SHF)-stem cells is considered a key biological process in the SHF regeneration, and the morphogenesis of cashmere fiber in cashmere goats. The miR-361-5p was essentially implicated in the induced activation of SHF-stem cells of cashmere goats, but its functional mechanisms are unclear. Here, we confirmed miR-361-5p was significantly downregulated in anagen SHF bugle of cashmere goats compared with that at telogen, and miR-361-5p expression was significantly lower in SHF-stem cells after activation than its counterpart before activation. Further, we found that miR-361-5p could negatively regulate the induced activation event of SHF-stem cells in cashmere goats. Mechanistically, through dual-luciferase reporter assays, miR-361-5p specifically bound with FOXM1 mRNA in SHF-stem cells of cashmere goats and negatively regulated the expression of FOXM1 gene. Also, through overexpression/knockdown analysis of FOXM1 gene, our results indicated that FOXM1 upregulated the expression of Wnt/β-catenin pathway related genes in SHF-stem cells. Moreover, based on TOP/FOP-flash Wnt report assays, the knockdown of miR-361-5p promotes the Wnt/β-catenin pathway activation through upregulating the FOXM1 expression in SHF-stem cells. Finally, we demonstrated that miR-361-5p negatively regulated the induced activation of SHF-stem cells through FOXM1 mediated Wnt/β-catenin pathway in cashmere goats.

Establishment of a high-content compatible platform to assess effects of monocyte-derived factors on neural stem cell proliferation and differentiation

During neuroinflammation, monocytes that infiltrate the central nervous system (CNS) may contribute to regenerative processes depending on their activation status. However, the extent and mechanisms of monocyte-induced CNS repair in patients with neuroinflammatory diseases remain largely unknown, partly due to the lack of a fully human assay platform that can recapitulate monocyte-neural stem cell interactions within the CNS microenvironment. We therefore developed a human model system to assess the impact of monocytic factors on neural stem cells, establishing a high-content compatible assay for screening monocyte-induced neural stem cell proliferation and differentiation. The model combined monocytes isolated from healthy donors and human embryonic stem cell derived neural stem cells and integrated both cell-intrinsic and -extrinsic properties. We identified CNS-mimicking culture media options that induced a monocytic phenotype resembling CNS infiltrating monocytes, while allowing adequate monocyte survival. Monocyte-induced proliferation, gliogenic fate and neurogenic fate of neural stem cells were affected by the conditions of monocytic priming and basal neural stem cell culture as extrinsic factors as well as the neural stem cell passage number as an intrinsic neural stem cell property. We developed a high-content compatible human in vitro assay for the integrated analysis of monocyte-derived factors on CNS repair.

Physical Forces in Regeneration of Cells and Tissues.

The ability to regenerate after the loss of a part is a hallmark of living systems and occurs at both the tissue and organ scales, but also within individual cells. Regeneration entails many processes that are physical and mechanical in nature, including the closure of wounds, the repositioning of material from one place to another, and the restoration of symmetry following perturbations. However, we currently know far more about the genetics and molecular signaling pathways involved in regeneration, and there is a need to investigate the role of physical forces in the process. Here, we will provide an overview of how physical forces may play a role in wound healing and regeneration, in which we compare and contrast regenerative processes at the tissue and cell scales.

Influence of growth regulators on callus induction and plant regeneration from anthers of Tagetes spp.

Marigold (Tagetes spp.) belongs to family Asteraceae, native to Mexico, is one of the most important flower crop grown commercially in different parts of India. The application of haploid techniques as anther culture can considerably accelerate marigold breeding programmes by providing homozygous doubled haploid (DH) lines for F1 hybrid seed production. Therefore, the objective of the present investigation was to study the effect of growth regulators for in vitro regeneration in both African marigold and French marigold genotypes viz., Pusa Basanti Gainda and Pusa Arpita, respectively for haploid induction. Among the different treatments tested for callus induction, anthers cultured on MS medium supplemented with 1.0 mg/l BAP + 1.0 mg/l 2,4-D + 45 g/l sucrose significantly induced highest (38.74%) callus in the shortest period of time (16 days). Among two genotypes tested, embryogenic callus induction (27.70%) was significantly higher in Pusa Arpita over Pusa Basanti Gainda (23.37%). Among the different regeneration treatments, the highest adventitious shoot bud induction (13.32%), maximum (1.09) number of buds/callus in shortest duration (19.47 days) was observed in anther derived callus cultured on MS medium supplemented with 2.0 mg/l BAP + 0.5mg/l NAA + 30 g/l sucrose. Among two genotypes evaluated for shoot bud induction, maximum (3.81%) regeneration was recorded in Pusa Arpita over Pusa Basanti Gainda (2.90%). In French genotype, the whole regeneration process was completed in 30 days whereas in African genotype it took nearly 40 days. This rapid regeneration system from anthers is highly useful in inducing haploids and di-haploids in African and French marigold lines, respectively.

Mesenchymal cells as the biological modifiers for stimulation and regulation of cellular and molecular healing and regeneration

Biologic modifiers are materials or proteins and factors that have the potential to alter the host tissue so as to stimulate or regulate the wound healing process. Classic examples of biologic modifiers are growth factors. Bioengineered materials are widely utilized due to their biocompatibility and degradability, as well as their moisturizing and antibacterial properties. One field of their application in medicine is to treat wounds by promoting tissue regeneration and improving wound healing. In addition to creating a physical and chemical barrier against primary infection, the mechanical stability of the porous structure of biomaterials provides an extracellular matrix (ECM)-like niche for cells. Growth factors are polypeptide molecules that control the growth, differentiation, and metabolism of cells during each of the three phases of wound healing. They are present throughout the body in only minute concentrations yet exert a powerful local influence on wound repair. They interact with specific receptors in the cell surface, leading to specific responses determined by the receptor-mediated signal transduction pathways within the target cells. Growth factors (GFs) and cytokines, which are secreted by the cells, are essential parts of the complex process of tissue regeneration and wound healing.

Photodynamic therapy mediated by methylene blue-loaded PEG accelerates skin mouse wound healing: an immune response.

Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic therapy (PDT) that uses methylene blue (MB) loaded with polyethylene glycol (PEG) (MB-PEG) hydrogel to accelerate wound healing process in mice. A dorsal skin incision with 6mm punch which topically subjected to MB-PEG hydrogel and a low-level laser light of red light to assess the regeneration process of wounded skin. A total of 63 adult male CD1 mice divided into normal group (no treatment) and other wound groups received different treatments of laser (650 ± 5nm and power intensity of 180 mW/cm2), MB-PEG, or PDT (MB-PEG followed by laser). The wound healing parameters were investigated by histological examination of the skin and measuring of proinflammatory cytokines at the early stage (48h) and a late one on day 21. at 48h, the score of tissue granulation, inflammation, and angiogenesis process were markedly improved in wounded groups that received MB + PEG combined with laser compared to the group treated with laser alone. On day 21, a significant improvement of the inflammation was detected in the group treated with MB + PEG plus laser compared to the other groups. At 48h, the upregulated serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the wound group were significantly (P < 0.001) reduced in the group treated with MB + PEG combined with laser. MB-PEG based hydrogel improves and accelerates wound closure in the context of laser compared to either single treatment.

Porous Organic Polymers for Efficient and Selective SO2 Capture from CO2‐rich Flue Gas

AbstractThe quest for effective technologies to reduce SO2 pollution is crucial due to its adverse effects on the environment and human health. Markedly, removing a ppm level of SO2 from CO2‐containing waste gas is a persistent challenge, and current technologies suffer from low SO2/CO2 selectivity and energy‐intensive regeneration processes. Here using the molecular building blocks approach and theoretical calculation, we constructed two porous organic polymers (POPs) encompassing pocket‐like structures with exposed imidazole groups, promoting preferential interactions with SO2 from CO2‐containing streams. Markedly, the evaluated POPs offer outstanding SO2/CO2 selectivity, high SO2 capacity, and an easy regeneration process, making it one of the best materials for SO2 capture. To gain better structural insights into the notable SO2 selectivity of the POPs, we used dynamic nuclear polarization NMR spectroscopy (DNP) and molecular modelling to probe the interactions between SO2 and POP adsorbents. The newly developed materials are poised to offer an energy‐efficient and environment‐friendly SO2 separation process while we are obliged to use fossil fuels for our energy needs.

Clinical efficacy of titanium prepared platelet rich fibrin in periodontal regeneration: A systematic review and meta-analysis

Background Periodontal regeneration therapies frequently involve autologous platelet concentrates (APCs). They can be used in sinus lift surgeries and socket preservation, among other clinical settings. Platelet rich fibrin (PRF) membrane has been used to treat gingival recession in individuals or groups of individuals using a coronally progressed or lateral pedicle flap. In the treatment of mixed periodontic endodontic lesion/furcation defect, PRF functions as a healing and interpositional biomaterial, filling a cystic cavity. PRF is known to help the bone regeneration process. In the last few years, efforts have been made to enhance the PRFs characteristics and quality. One of them is titanium platelet rich fibrin (T-PRF). Third-generation platelet concentrate no longer contains silica, and its preparation in glass vacuum containers, that no longer creates any known concerns. The effectiveness PRF’s has been evaluated in connective tissue and bone repair. The aim of this study is to compare T-PRF to other platelet concentrates and different treatment modalities for periodontal regenerative procedures. Methods A protocol of this systematic review have been registered in prospero (CRD42022293545). The online database searched were PUBMED, COCHRANE for published articles up to November 2022 without language restrictions. Studies in trial registers, handsearching, bibliographic references of relevant articles were also checked. Data collection and analysis was done by individual authors. Independent eligibility assessments were conducted by four review authors. Then, using the standard Cochrane methodology, four review authors extracted the data and evaluated the risk of bias for individual studies. We developed “Summary of findings” tables and used GRADE to evaluate the evidence. Results Three studies were included for meta-analysis. Results of meta-analysis supported that T-PRF is effective for correction of both hard and soft tissue defects. Conclusions The overall qualitative and quantitative analysis suggest that T-PRF has superior structural properties and thicker fibrin network for ensuring predictable success periodontal regenerative procedures.

#2145 Sexual dimorphism in kidney regenerative capacity decline and in progressive tubular cell polyploidization during aging

Abstract Background and Aims Aging is characterized by a progressive kidney function decline, resulting in chronic kidney disease (CKD), which is steeper in men than in women. However, sex-related differences in mechanisms underpinning CKD development during aging still remain to be clarified. In most organs regenerative capacity declines overtime from a pool of resident stem cells leading to tissue aging. In the kidney, we have revealed that two adaptive responses co-exist to recover kidney function after injury. On one hand a population of renal progenitors (RPC), which is interspersed among parietal epithelial cells of Bowman's capsule and tubular cells (TC) of nephron segments, proliferate and generate new podocytes and TC to recover structural integrity during the regenerative processes occurring in glomerular and tubular diseases. On the other, TC enter the alternative cell cycles to become polyploid in order to increase their functional capacity and maintain the residual kidney function after injury. However, a continuous TC polyploidization comes with the long term trade-offs (fibrosis and senescence), driving CKD. Here, we aimed to investigate the role of sexual dimorphism in these two different adaptive responses during aging. Method To trace RPC (Pax2+cells) we used the inducible Pax2/Confetti or Pax2/mTmG mice (RPC are randomly labelled by one of the four fluorescent reporter genes or with GFP respectively). To study polyploid TC, we used the inducible Pax8/FUCCI2aR mice (polyploid TC are identified by expression of cell cycle fluorescent proteins in combination with DNA content analysis). Mice were analyzed at 2, 5, 12 and 20 months of age. scRNA sequencing was performed at 2 and 20 months of age. Results Pax2/Confetti mice revealed that the number of Pax2+RPC either of the Bowman's capsule or in tubules was higher in female than in male mice at all ages. Specifically, tracing analysis during aging showed that in females Pax2+RPC of the Bowman's capsule generated new podocytes, resulting in glomeruli with a better integrity of the slit-diaphragm compared with aged males. Moreover, tubular Pax2+RPC in females clonally expanded, generating a higher number of clones, which were longer than those in males. scRNAseq analysis on kidneys showed that females were endowed with a greater number of Pax2+RPC with a higher expression of Pax2 than males, suggesting that RPC in females kept a higher regenerative capacity than males during aging. Simultaneously, analysis of tubular polyploidy demonstrated that, whereas in females the polyploid fraction progressively increased, it was drastically reduced in males during aging. These results suggested that whereas in females the increase of polyploid TC provided a better maintenance of kidney function overtime, loss of polyploid response in males made them more susceptible to develop CKD. Indeed, aged male mice showed a higher percentage of polyploid TC undergoing further cycles of polyploidization, which were associated with fibrosis and senescence. In agreement with these findings, we observed a progressive kidney function decline along with an increase of glomerulosclerosis, interstitial fibrosis and blood pressure, which were significantly greater in males than in females. Conclusion Female mice showed a higher regenerative and polyploid response compared to male mice, aimed likely to cope kidney function decline during aging. These results reveal the intriguing role of a new kidney adaptive response, which may explain the higher susceptibility of males to develop a more premature CKD during aging.

#2723 10-hydroxy-trans-2-decenoic and nonanoic acid delayed senescence in adult renal progenitor cells and increased the anti-aging Klotho protein secretion

Abstract Background and Aims Recent investigations have elucidated the complex system involving human adult renal stem/progenitor cells (ARPCs) and their pivotal role in maintaining homeostasis and in facilitating regenerative processes within the adult kidneys. CD133+/CD24+ ARPCs can repair several kinds of renal damage but their reparative properties can be compromised by the cell senescence, contributing to renal aging and impaired damage repair. The functional marker CD133 inversely correlates with cellular senescence and plays a crucial role in the ARPC regulation. Decreased protective factors, hypoxia, and microenvironmental stress drive increasingly cell senescence, disordered inflammation and renal fibrosis. The resulting fibrosis, senescence, and microvascular rarefaction exacerbate damage and promote chronic kidney disease (CKD) progression. In this study, we explore the impact of natural molecular compounds and drugs on slowing down and delaying ARPC senescence. Method ARPCs were treated with the following compounds for 48 hours: nonanoic acid (1 mM), 3-decenoic acid (1 mM), 10-hydroxy-trans-2-decenoic acid (10-HDA, 25uM), and Valproic acid (VPA, 1 mM), either individually or in combination. Lipid microvesicles were used to transmit the bioactive molecules. FACS was used to determine the CD133 levels. the β-galactosidase assays were used to determine cell senescence status. Western blots were performed to assess p16, p53 and p21 markers. Results Cytofluorimetry results demonstrated an increase in the expression of CD133, the inverse cell senescence marker, both following stimulation with decenoic (fold change = 1.8, p = 0.0053) and nonanoic acid (FC = 1.3, p = 0.0056), and with VPA (FC 2, p = 0.0036). Simultaneously, the number of senescent cells decreased, as confirmed by the β-galactosidase assay (FC = 0.13, p = 0.0005). The treatment with decenoic and nonanoic acid also restored high levels of the lncRNA HOTAIR (FC = 14.6 for nonanoic acid and 12.7 for 10-HDA; p = 0.05), that in turn promoted the secretion of the α-Klotho anti-aging protein (FC = 3.1; p = 0.01). Additionally, the western blot analysis revealed that the 10-HDA decreased the expression of cell senescence markers, p16 (FC = 1.6, p = 0.05), p53 (FC = 1.8, p = 0.05) and p21 (FC= 3.7, p = 0.05). Moreover, the nonanoic acid reduced the expression of p16 (FC = 1.8, p = 0.05), p53 (FC = 2, p = 0.05) and p21 (FC= 2.6, p = 0.0007). Also, their combination contributes to decrease p16 (FC = 1.9, p = 0.05), p53 (FC = 1.3, p = 0.05) and p21 (FC= 2.5, p = 0.05). Conclusion This study identifies specific molecules capable of reducing or delaying ARPC senescence. In particular, the two natural compounds 10-HDA and nonanoic acid can also enhance the capacity of renal progenitors to secrete the α-Klotho protein whose decline prevention by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. These findings present potential therapeutic avenues for delaying or mitigating the progression of CKD.

Acquisition of epithelial plasticity in human chronic liver disease.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized1-4, but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this processcould open new therapeutic avenues in the management of chronic diseases.

Establishment of an efficient regeneration system of ‘ZiKui’ tea with hypocotyl as explants

Zikui (Camellia sinensis cv. Zikui) is a recently discovered cultivar of local purple tea in Guizhou, China. It is a purple leaf bud mutation material of Meitan Taicha (Camellia sinensis cv. ‘Meitan-taicha’) ‘N61’ strain, which is an important local germplasm resource in Guizhou. It is also a model plant for the study of anthocyanins, but the limited germplasm resources and the limitation of traditional reproduction hinder its application. Here, an efficient regeneration system is established by using hypocotyl as explants for the first time. Different plant growth regulators (PGRs) are evaluated during different regeneration processes including callus and root induction. According to our findings, using the optimal disinfection conditions, the seed embryo contamination rate is 17.58%. Additionally, the mortality rate is 9.69%, while the survival rate is measured as 72.73%. Moreover, the highest germination rate of 93.64% is observed under MS + 2.40 mg/L GA3 medium conditions. The optimal callus induction rate is 95.19%, while the optimal adventitious bud differentiation rate is 20.74%, Medium with 1.6 mg/L IBA achieved 68.6% rooting of the adventitious shoots. The survival rate is more than 65% after 6 days growth in the cultivated matrix. In summary, our research aims to establish a regeneration system for Zikui tea plants and design a transformation system for tea plant tissue seedlings. This will enable transfer of the target gene and ultimately facilitate the cultivation of new tea varieties with unique characteristics.

Promoting tissue repair using deferoxamine nanoparticles loaded biomimetic gelatin/HA composite hydrogel

To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferation in vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.

IMPACT OF QUERCETIN ON PATHOMORPHOLOGICAL CHARACTERISTICS OF MANDIBULAR BONE IN RATS FOLLOWING ITS FRACTURE UNDER CHRONIC ALCOHOL INTOXICATION

This study aims at investigating the impact of water-soluble form of quercetin on the pathomorphological characteristics of the mandibular bone in rats following its incomplete fracture under chronic alcohol intoxication was investigated. Fourteen white male Wistar rats weighing 190-240 g were randomly divided into two groups: Group 1 comprised rats with incomplete mandibular fractures under chronic alcohol intoxication; animals in Group 2 received daily intraperitoneal injections of water-soluble quercetin (corvitin) in a dose of 10 mg/kg of quercetin for 14 days following the injury induction. It has been shown that chronic alcohol intoxication hinders reparative regeneration of bone tissue after an incomplete mandibular fracture, and is accompanied by a decrease in the relative amount of reticulofibrous bone tissue and fibroblastic cellular elements at the injury site, especially mature fibroblasts, as well as by delayed maturation of granulation tissue. Under experimental conditions, quercetin administration significantly contributed to normalizing the regenerative process by the 14th day of the posttraumatic period. This normalization was evidenced by increased relative amounts of reticulofibrous bone tissue, prevalence of fibroblastic cells in granulation tissue, and accelerated formation of the regenerate blood microcirculatory channel.

Green and sustainable hydrogels based on quaternized chitosan to enhance wound healing

Hydrogel-based biomaterials applied as wound dressings provide the wound with a moist environment, which facilitates tissue regeneration through granulation and re-epithelialization. The inherent flexibility and adjustable architecture of hydrogels enables incorporation of cells, antimicrobial drugs, growth factors, and bioactive compounds, which leads to expediting wound contraction and enhancing the regeneration process. The utilization of natural polysaccharides, particularly chitosan, as a green and one of the most sustainable biomaterials among renewable resources, has been widely practised in wound healing because of its promising cost-effectiveness, biocompatibility, and biodegradability. However, the challenge of limited solubility of chitosan at neutral or basic media (pH ≥ 6.5) has been pinpointed. The exploration of quaternary chitosan hydrogels was a big step to combat its low solubility through the contribution of a quaternary ammonium group that improves the hydrophilicity and additionally brings about antibacterial activity over a wide range of pH. This review summarizes the latest progress in using hydrogel dressings based on quaternized chitosan for wound regeneration, encompassing various aspects such as hemostasis, antibacterial activity, antioxidant properties, and overall wound healing efficacy. Furthermore, the present review addresses the existing challenges and proposes possible solutions to enlarge development avenues in pursue of optimizing wound regeneration performance of quaternized chitosan-based hydrogels in prospect.

Toward Sustainable Lithium Iron Phosphate in Lithium‐Ion Batteries: Regeneration Strategies and Their Challenges

AbstractIn recent years, the penetration rate of lithium iron phosphate batteries in the energy storage field has surged, underscoring the pressing need to recycle retired LiFePO4 (LFP) batteries within the framework of low carbon and sustainable development. This review first introduces the economic benefits of regenerating LFP power batteries and the development history of LFP, to establish the necessity of LFP recycling. Then, the entire life cycle process and failure mechanism of LFP are outlined. The focus is on highlighting the advantages of direct recycling technology for LFP materials. Directly regenerating LFP materials is a very promising solution. Directly regenerating spent LFP (S‐LFP) materials can not only protect the environment and save resources, but also directly add lithium atoms to the vacancies of missing lithium atoms to repair S‐LFP materials. At the same time, simply supplementing lithium to repair S‐LFP simplifies the recovery process and improves economic benefits. The status of various direct recycling methods is then reviewed in terms of the regeneration process, principles, advantages, and challenges. Additionally, it is noted that direct recycling is currently in its early stages, and there are challenges and alternative directions for its development.

Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts.

Background: Although xenografts have shown successful results in GBR procedures due to their osteoconductive properties, many authors have opted to add co-adjuvant drugs to favor osteogenesis and differentiate cells into an osteoblastic lineage. Metformin has been shown to have bone-protective properties, regulating osteoclast differentiation, as well as the ability to promote osteoblast mineralization and differentiation. The present study aimed to evaluate the effect of the local application of a 1% metformin solution on bone neoformation in the treatment of an experimental bone defect in a guided bone regeneration animal model with a particulated bovine hydroxyapatite xenograft with hyaluronate. Methods: With this purpose in mind, two critical defects with 8 mm diameter and 0.5 mm depth were created in eight male New Zealand rabbit calvarias. Titanium cylinders were fixed in each defect and filled with particulate hydroxyapatite of bovine origin and sodium hyaluronate, with sterile injectable saline added to the control group and sterile 1% metformin solution added to the test group. At 6 weeks, the animals were euthanized, and samples were obtained and prepared for histomorphometric analysis. Results: A higher percentage of new bone formation was observed in the metformin samples than in the control samples, both in the region closest to the animal's calvaria and in the most distal region analyzed. A higher average bone-biomaterial contact percentage was observed in the samples, with metformin in both the proximal and distal regions. There was no statistically significant difference in the mean value in either region in both parameters. Conclusion: The local application of a 1% metformin solution in an animal model of guided bone regeneration with particulate bovine hydroxyapatite and hyaluronate resulted in greater bone neoformation and xenograft osseointegration than in the control group.