Search Results (183)

Chronic cutaneous wounds and traumatic skin injuries remain a major clinical challenge, characterized by dysregulated healing phases, high susceptibility to microbial infection, and suboptimal response to conventional therapies. Stem cell-derived exosomes (SC-Exos) have emerged as a paradigm-shifting, cell-free nanotherapeutic platform that harnesses the paracrine secretome of stem cells while avoiding the immunological and proliferative complications inherent to direct cell transplantation. Exosomes derived from diverse stem cell sources orchestrate multifactorial wound repair by modulating key cellular signaling cascades and transcriptomic programs that collectively regulate inflammation, angiogenesis, re-epithelialization, extracellular matrix (ECM) remodeling, and scar formation. Beyond their intrinsic regenerative capacity, SC Exos can be engineered using direct strategies (cargo loading, surface modification, biomaterial integration, and conjugation) and indirect approaches (genetic engineering, pretreatment, and preconditioning of parental cells), thereby enabling spatially controlled and temporally sustained exosome release at wound sites with enhanced bioavailability and therapeutic efficacy. In parallel, biomaterial-assisted delivery platforms, including hydrogels, scaffolds, and nanofibers, enhance exosome retention, stability, and controlled-release profiles within the wound microenvironment, thereby further potentiating tissue repair. This review provides a comprehensive overview of recent advances in SC Exos for wound healing and skin regeneration. We first summarize exosome biogenesis, molecular composition, and the distinctive characteristics of exosomes derived from different stem cell sources, along with preclinical evidence supporting their efficacy in cutaneous repair. We then critically examine exosome engineering strategies and biomaterial-integrated delivery systems that augment and fine-tune therapeutic outcomes. Finally, we discuss the current status of clinical trials of SC Exo-based therapies, key manufacturing and regulatory challenges, and future directions for translating these nanoscale, cell-free therapeutics into advanced, personalized wound management. Full article

Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable of mimicking native bone properties to promote effective regeneration. In this study, silk fibroin (SF)-based composite scaffolds incorporating β-tricalcium phosphate (β-TCP) and poly-ε-caprolactone (PCL) were synthesized using a simple and innovative cryogenic foaming method. The proposed fabrication technique overcomes many limitations of current synthesis methods, such as long processing times, the use of solvents, and reliance on complex, energy-intensive equipment. The composites were characterized using infrared spectroscopy to confirm the incorporation of all three components and their chemical bond arrangements. µ-CT, SEM, and ESEM analyses revealed that SF/β-TCP/PCL scaffolds exhibited great porosity and dynamic interaction with water while preserving pore morphology in wet environments. Swelling behavior, indirect cytotoxicity, and cell proliferation tests recognized the greater performance of SF/β-TCP/PCL scaffolds in promoting long-term cell proliferation, maintaining superior mechanical properties. These findings indicate that the proposed original, simple, and relatively low-cost manufacturing approach enabled the fabrication of scaffolds with excellent mechanical performances, controlled and stable porosity under both dry and physiological-like conditions, and high biocompatibility. The resulting constructs demonstrated promising results for cell proliferation and osteoconductive behavior, supporting their potential suitability as artificial bone substitutes. Full article

Micro-public space (MPS) regeneration is typically evaluated at the point of delivery, yet long-term performance depends on whether everyday stewardship can be sustained thereafter. This study reframes neighbourhood social capital as a governance–environment signal reflecting coordination capacity and examines whether residents’ willingness to participate in post-regeneration co-management is primarily appraisal-driven (perceived value, attitude, and perceived behavioural control) or coordination-driven via a residual direct channel consistent with routine governance. A cross-sectional survey of adults residing within walkable catchments of five regenerated MPS sites in Nan’an District, Chongqing, China ($N=477$), was conducted. An integrated Stimulus–Organism–Response × TPB model was estimated using WLSMV with ordered categorical indicators; indirect effects were assessed via bias-corrected bootstrap confidence intervals. Coordination capacity was strongly associated with perceived value, participation attitude, and perceived behavioural control. In the joint model, only perceived value retained a statistically reliable positive association with stewardship willingness, whereas the incremental contributions of attitude and perceived behavioural control were negligible once the stimulus was included. A residual direct association from coordination capacity to willingness persisted beyond the appraisal block, supporting a direct-dominant interpretation; bootstrap analyses yielded no robust evidence for mediation (BCa 95% CIs crossed zero). These findings suggest that sustaining regenerated micro-spaces requires low-friction governance designs that minimise coordination costs, reinforce soft accountability, and render institutional responsiveness visible to residents. Full article

The immune microenvironment critically influences bone healing, particularly in the oral cavity where inflammation and microbial biofilms can compromise regeneration. Plant-derived extracellular vesicles (PDEVs) offer a biocompatible means to modulate immune responses, and apple-derived extracellular vesicles (ADEVs) have shown antioxidant and anti-inflammatory activity, although their osteoregenerative potential remains unclear. Here, we investigate the indirect effects of ADEVs on bone regeneration by assessing how their immunomodulatory action on macrophages influences the osteogenic commitment of human dental pulp stem cells (DPSCs). ADEVs were isolated, characterized, and applied to THP-1-derived macrophages to evaluate polarization via morphology and immunofluorescence for M1 (iNOS) and M2 (ARG1) markers. Then, the extracellular vesicles (EVs) from untreated and ADEV-treated macrophages were isolated and applied to DPSCs. All EVs were efficiently internalized by both macrophages and DPSCs. Treated macrophages shifted toward an M2-like phenotype, and macrophage-derived EVs (MDEVs) promoted stem cell morphological features consistent with osteogenic activation. These findings suggest that ADEVs promote osteoregeneration indirectly by influencing macrophage polarization and modifying the osteoactive cargo of MDEVs, thereby supporting their potential in cell-free, immunomodulatory approaches for oral bone regeneration. Full article

The natural regeneration of planted forests in karst landscapes is severely constrained by extreme substrate heterogeneity and fragile edaphic conditions. However, the relative importance and interaction pathways of environmental versus stand structural drivers remain poorly quantified. In this study, 54 plots (10 m × 10 m) were surveyed across Cupressus funebris plantations in the karst landscape of the Lijiang River Basin, southern China. To identify the key factors and causal pathways governing regeneration, redundancy analysis (RDA), variation partitioning, partial least squares structural equation modeling (PLS-SEM), and threshold analyses were applied. Regeneration exhibited pronounced spatial heterogeneity, with 42.6% of plots showing complete recruitment failure and a characteristic inverted J-shaped size class distribution. The analysis identified soil rock fragment content (as a negative constraint) and canopy gap area (as a positive driver) as the two dominant predictors. PLS-SEM revealed that environmental factors influence regeneration primarily through an indirect pathway mediated by stand structure ($R^2=0.683$) rather than through direct effects. Threshold analyses identified quantitative benchmarks for key drivers, including a gap area breakpoint of approximately 10 ${\mathrm{m}}^2$ and a presence–absence effect of soil rock fragments. These findings contribute to a more sophisticated mechanistic understanding of forest regeneration in karst ecosystems and provide an empirical foundation for silvicultural management that aims to encourage natural regeneration and ecological restoration of degraded karst plantations. Full article

Urban public spaces are an essential component of everyday life in urban communities, and micro public spaces have become an important vehicle for improving living environment quality and enhancing ecological benefits in community renewal within built-up areas. From an economic perspective, this study focuses on the quantification of carbon value generated through the renewal of micro public spaces. Four micro public spaces of comparable size but differing locational and functional characteristics, completed in Wuhan in 2023, were selected as case studies. Plant carbon sequestration was estimated using the biomass expansion factor method combined with field-based forestry surveys, while indirect emission reduction associated with residents’ outdoor activities was assessed through spatiotemporal observations of user behavior. These results were further translated into carbon value based on China’s carbon trading standards to support comparative analysis and design-oriented recommendations. The results indicate that direct sequestration significantly outweighs indirect reduction: the carbon storage density of trees ranges from 0.40 to 1.97 kg/m², with the total storage of HRP reaching 11,587.36 kg; in contrast, annual indirect reduction from resident activities is only 1.34–141.19 kg. Carbon sequestration performance is strongly influenced by the presence of large trees, while micro public spaces located in newly developed and commercial areas exhibit substantially lower emission reduction efficiency than those in older and densely populated residential neighborhoods. In addition, the functional attributes of micro public spaces shape age-specific use patterns, thereby significantly affecting emission reduction outcomes. Based on these findings, targeted optimization strategies for micro public space renewal are proposed to support people-oriented, sustainable, and systematic low-carbon urban regeneration. Full article

Research in implant dentistry has predominantly focused on bone regeneration, osseous volume maintenance, and successful osseointegration. However, soft tissue healing, which influences implant functional sealing, long-term stability, and esthetic integration, remains underexplored. This study investigated the effects of three xenogenic bone substitutes on gingival healing in vitro. Three experimental groups were established using extracts from bone substitutes diffusing through the OsteoBiol^® Evolution collagen membrane: two collagenated substitutes, OsteoBiol^® Gen-Os^® (Gen-Os) and OsteoBiol^® GTO^® (GTO), and one inorganic substitute, Bio-Oss^® (Bio-Oss). The substitutes were prepared in test tubes, and the extracts diffusing through the collagen membrane were used to evaluate human gingival cell (hGC) proliferation (MTT assay), migration (scratch assay), and growth factor release (ELISA). Angiogenic potential was assessed by endothelial cell proliferation, recruitment (Boyden chambers), and organization (Matrigel^® assays). The indirect interaction between stimulated gingival cells and human bone marrow mesenchymal stem cells (hMSC) was investigated by analyzing hMSC recruitment and osteogenic BMP-2 secretion. Collagenated GTO and Gen-Os significantly enhanced hGC proliferation and migration in the scratch assay, with 1.8-fold and 1.6-fold increases, respectively, compared to control. All three substitutes enhanced neoangiogenesis in vitro. VEGF and FGF-2 secretion was significantly higher with GTO, showing 5-fold and 5.7-fold increases, respectively, resulting in a 3.7-fold increase in tube formation compared to control. Collagenated materials promoted hMSC recruitment, whereas BMP-2 secretion was not affected by any material. The observed effects were higher with the collagenated Gen-Os and GTO, with 2.5-fold and 2.8-fold increases, respectively, than with the non-collagenated Bio-Oss, which showed a 1.5-fold increase. These findings demonstrate that collagenated bone substitutes enhance gingival healing and angiogenic potential through barrier membranes and confirm that stimulated gingival cells indirectly promote hMSC recruitment, indicating that bone substitute effects extend beyond bone regeneration to include soft tissue healing and inter-tissue communication. Full article

In this paper, the effects of Poland’s forest management evolution after 1945 on forest biodiversity at the genetic level were analysed. Forest biodiversity changes across the two politically and economically different eras (socialism, 1945–1989, and democracy, from 1990) are interpreted using three indirect indicators: forest regeneration and expansion, tree genetic resources, and threatened forest species. In the era of socialism, the total area of regeneration and reforestation gradually decreased, with these activities relying almost exclusively on cultivated reproductive material. After 1990, there was a relative stabilisation in the total area, with a noticeable increase in the use of natural processes to diversify the tree gene pool. Work on verifying and protecting the forest tree seed base, as well as on assessing the conservation status of an increasingly wide range of organisms, began in the era of socialism; however, it was intensified only in the era of democracy. In the latter case, the increase in the number of endangered species suggests a potentially negative trend. However, the actual assessment of the changes is not entirely clear due to subsequent changes in threat classification and increased knowledge of the occurrence of individual species. Dilemmas and problems related to the following issues require further discussion and resolution or implementation of further measures: the consequences of past choices regarding planted trees; the use of natural regeneration; the reduction in the forest tree gene pool as a result of artificial selection; incomplete knowledge about threats to the forest gene pool; the continued impact of threats and the possibilities for counteracting them; and securing funding for measures to protect biodiversity at the genetic level. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become highly prevalent worldwide, and its pathogenesis and progression mechanisms remain incompletely understood. An increased activation of innate immune cells in the liver contributes to hepatic fibrogenesis via a chronic loop of inflammation and regeneration processes. Among them are mast cells (MCs), whose role in hepatic cirrhosis secondary to MASLD remains poorly studied. Our aim was to evaluate differences in MC density in cirrhotic liver tissue among patients with MASLD and other chronic liver disease etiologies. For this, a retrospective study of MC count was performed in cirrhotic liver explants obtained from MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH). We included a control group of subjects without liver damage. Tryptase-positive MCs were identified by indirect immunofluorescence and quantified as MC density per low-power field (MC/LPF). Group differences were analyzed using the Kruskal–Wallis test with Dunn’s multiple comparisons, considering p < 0.05 as statistically significant. A significantly higher MC density was observed in MASLD, ALD, and AIH patients compared with the control group. The group analysis showed that ALD patients exhibited higher MC density than AIH, with no observed difference between ALD and MASLD. MC density was correlated positively with tobacco smoking and alcohol use in the full analyzed group, suggesting them as risk factors of high MC liver infiltration. We conclude that MC density is augmented in MASLD-related cirrhosis, highlighting potential links between lifestyle factors and MC-mediated hepatic inflammation. Future studies should explore the mechanisms driving this association and evaluate whether targeting MCs could help mitigate fibrosis progression. Full article

Mechanobiology plays a pivotal role in skeletal development and bone remodeling. Mechanical signals such as matrix stiffness, fluid shear stress, and hydrostatic pressure activate the Runt-related transcription factor 2 (RUNX2) bone-specific transcription factor through pathways including the mitogen-activated protein kinase (MAPK) signaling cascade and yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) effectors. RUNX2 itself affects chromatin remodeling and nuclear architecture via Lamin A/C and Nesprin 1, thereby directing osteogenic differentiation. Thus, RUNX2 acts both as a mechanosensor and mechanoregulator, whereas RUNX2’s mechanosensitivity has been leveraged as a target to achieve bone regeneration. Notably, post-translational modifications and epigenetic alterations can orchestrate this regulation, integrating metabolic and circadian signals. However, due to RUNX2’s nuclear localization, its targeting remains a challenging issue. To this end, indirect targeting, through mammalian/mechanistic target of rapamycin complex 1 (mTORC1) or microRNAs (miRNAs), offers new strategies to employ biomechanics in an attempt to intervene with bone diseases driven by mechanical cues or degeneration, and ultimately repair and regenerate the damaged tissues. Herein we critically elaborate upon molecular aspects of RUNX2 regulation towards exploitation at the clinical level. Full article

Background/Objectives: Increasing evidence points to hypoxia and inflammation as two major causes of compromised ovarian function. Increased oxidative stress under hypoxic conditions can damage cellular components, leading to the dysfunction and apoptosis of granulosa cells (GCs). The inflammatory response induced by hypoxia may further impair the function of the ovaries and contribute to the development of premature ovarian insufficiency (POI). In animal models of premature ovarian failure, research has demonstrated that the transplantation of mesenchymal stem cells (MSCs) can enhance reproductive outcomes, increase the number of functioning ovarian follicles, and restore estradiol production. However, the specific mechanisms underlying the observed positive results are not well understood. Methods: The present study provides a comparative analysis of how MSCs influence human GC function under inflammatory and hypoxic conditions, using three different experimental approaches: direct co-culture, indirect co-culture with transwell cell culture inserts, and treatment with MSC-derived conditioned medium (MSCcm). Results: Inflammation significantly suppressed GC estradiol secretion and increased apoptosis. MSCs increased estradiol secretion in normal and hypoxic culture conditions when co-cultured directly with GCs. Our results also showed that, under inflammation, MSCs tended to decrease GC proliferation and that hypoxia alone did not have an effect on GC estradiol secretion or proliferation. Conclusions: The study emphasizes the dual nature of MSCs, which largely determines their effects on other cell types, and the need for the condition-specific optimization of MSC therapies for ovarian regeneration. Full article

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5′-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell–cell and cell–matrix interactions, reducing the regenerative and reparative potential of the dentin–pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp. Full article

The ultimate objective of this research is to concentrate nutrients—nitrogen (N), phosphorus (P), and potassium (K)—and produce process water from a chemically pretreated liquid digestate using an FO-RO hybrid process. However, in this manuscript, we assessed the suitability of (NH₄)₂SO₄ and NaCl as draw solutes in a series of FO experiments employing a commercial CTA membrane and DI water as the feed solution. We also examined the regeneration of (NH₄)₂SO₄ in a series of RO experiments at various feed concentrations and pressures using a commercial polyamide (PA) thin-film composite (TFC) membrane, ACM4. Additionally, the RO experiments enabled the experimental determination of the osmotic pressure of (NH₄)₂SO₄ at various feed concentrations, which is crucial for designing the FO part of the hybrid process. The CTA membrane exhibited a significantly greater selectivity for (NH₄)₂SO₄ than for NaCl at any osmotic pressure. The RO experiments demonstrated the possibility of reconcentrating (NH₄)₂SO₄ to 0.5 mol/L, with a corresponding water flux of 60 L h⁻¹ m⁻² at 40 bars. The experimentally determined osmotic pressures were lower than those predicted by van’t Hoff’s equation but were consistent with those reported in the literature using an indirect hygrometric method. Full article

Assessing the extent and magnitude of wildlife impact on forest regeneration (e.g., % browsed seedlings or reduction in regeneration density) remains a central challenge. This study explores the potential of unmanned aircraft systems (UAS) to quantify wildlife impact through the integration of drone-based thermal surveys and vegetation assessments. Specifically, it evaluates whether UAS-derived wildlife density estimates can be linked to browsing intensity and regeneration structure, thereby enabling an indirect assessment of silviculturally relevant forest dynamics. By combining remotely sensed wildlife data with field-based vegetation inventories, the study aims to identify measurable relationships between structural forest characteristics and browsing effects. This approach contributes to the development of spatially efficient, objective, and reproducible monitoring methods at the forest–wildlife interface. Ultimately, the study provides a novel framework for integrating modern remote sensing technologies into wildlife–ecological monitoring and for improving adaptive, evidence-based management in forest ecosystems increasingly affected by high ungulate densities and climate-related stressors. Two silviculturally contrasting study areas were selected: a broadleaf-dominated mixed forest in Hesse, where high ungulate densities were expected, and a pine-dominated site in Brandenburg, anticipated to experience lower browsing pressure. Thermal surveys were conducted using a DJI Matrice 30T drone equipped with a high-resolution infrared camera to detect and geolocate wildlife. In parallel, browsing impact was assessed using a modified circular transect method (“Neuzeller method”). Regeneration was recorded by tree species, height class, and browsing intensity. Statistical analyses and GIS-based spatial visualizations were used to examine the relationship between estimated ungulate densities and browsing levels. Results revealed clear differences in wildlife abundance and browsing intensity between the two sites. In the Heppenheim forest, roe deer densities exceeded 40 individuals per 100 ha, correlating with high browsing pressure—particularly on ecologically and silviculturally valuable species such as sycamore maple and sessile oak. In contrast, the Rochauer Heide exhibited lower densities and a comparatively moderate browsing impact, although certain tree species still showed signs of selective pressure. This study demonstrates that drone-based wildlife monitoring offers an innovative, non-invasive means to indirectly evaluate forest structural conditions in regeneration layers. The findings highlight the relevance of UAV-supported methods for evidence-based wildlife management and the adaptive planning of silvicultural measures. The method enhances transparency and spatial resolution in forest–wildlife management and supports evidence-based decision-making in times of ecological and climatic change. Full article

Somatic embryogenesis (SE) is a morphogenetic pathway widely employed in the commercial micropropagation of plants. This route enables the generation of somatic embryos from somatic tissues, which give rise to complete (bipolar) plants that develop like zygotic embryos. SE can proceed via direct or indirect pathways, and both approaches have been adapted not only for large-scale clonal propagation but also for the regeneration of genetically modified plants. In this context, SE can be harnessed as a versatile platform for recombinant protein production, including vaccine antigens and therapeutic proteins, by combining plant tissue culture with genetic transformation strategies. Successful examples include non-model plants, as Daucus carota and Eleutherococcus senticosus expressing the cholera and heat-labile enterotoxin B subunits, respectively; Oryza sativa, Nicotiana tabacum, and Medicago sativa producing complex proteins such as human serum albumin (HSA), α₁-antitrypsin (AAT), and monoclonal antibodies. However, challenges remain in optimizing transformation efficiency, scaling up bioreactor-based suspension cultures, and ensuring proper post-translational modifications under Good Manufacturing Practice (GMP) standards. Recent advances in synthetic biology, modular vector design, and glycoengineering have begun to address these limitations, improving control over transcriptional regulation and protein quality. This review highlights the application of SE as a biotechnological route for recombinant protein production, discusses current challenges, and presents innovative strategies and perspectives for the development of sustainable plant-derived biopharmaceutical systems. Full article