Essential elements for spatiotemporal delivery of growth factors within bio-scaffolds: A comprehensive strategy for enhanced tissue regeneration.

The precise delivery of growth factors (GFs) in regenerative medicine is crucial for effective tissue regeneration and wound repair. However, challenges in achieving controlled release, such as limited half-life, potential overdosing risks, and delivery control complexities, currently hinder their clinical implementation. Despite the plethora of studies endeavoring to accomplish effective loading and gradual release of GFs through diverse delivery methods, the nuanced control of spatial and temporal delivery still needs to be elucidated. In response to this pressing clinical imperative, our review predominantly focuses on explaining the prevalent strategies employed for spatiotemporal delivery of GFs over the past five years. This review will systematically summarize critical aspects of spatiotemporal GFs delivery, including judicious bio-scaffold selection, innovative loading techniques, optimization of GFs activity retention, and stimulating responsive release mechanisms. It aims to identify the persisting challenges in spatiotemporal GFs delivery strategies and offer an insightful outlook on their future development. The ultimate objective is to provide an invaluable reference for advancing regenerative medicine and tissue engineering applications.

Collagen-based scaffolds with high wet-state cyclic compressibility for potential oral application.

Soft tissue substitutes have been developed to treat gingival recessions to avoid a second surgical site. However, products of pure collagen for clinical application lack their original mechanical strengths and tend to degrade fast in vivo. In this study, a collagen-based scaffold crosslinked with oxidized sodium alginate (OSA-Col) was developed to promote mechanical properties. Compared with commercial products collagen matrix (CM) and collagen sponge (CS), OSA-Col scaffolds presented higher wet-state cyclic compressibility, early anti-degradation ability, similar hemocompatibility and cytocompatibility. Furthermore, in the subcutaneous implantation experiment, OSA2-Col3 scaffolds showed better anti-degradation performance than CS scaffolds and superior neovascularization than CM scaffolds. These results demonstrated that OSA2-Col3 scaffolds had potential as a new soft tissue substitute for the treatment of gingival recessions.

Tailoring the Swelling-Shrinkable Behavior of Hydrogels for Biomedical Applications.

Hydrogels with tailor-made swelling-shrinkable properties have aroused considerable interest in numerous biomedical domains. For example, as swelling is a key issue for blood and wound extrudates absorption, the transference of nutrients and metabolites, as well as drug diffusion and release, hydrogels with high swelling capacity have been widely applicated in full-thickness skin wound healing and tissue regeneration, and drug delivery. Nevertheless, in the fields of tissue adhesives and internal soft-tissue wound healing, and bioelectronics, non-swelling hydrogels play very important functions owing to their stable macroscopic dimension and physical performance in physiological environment. Moreover, the negative swelling behavior (i.e., shrinkage) of hydrogels can be exploited to drive noninvasive wound closure, and achieve resolution enhancement of hydrogel scaffolds. In addition, it can help push out the entrapped drugs, thus promote drug release. However, there still has not been a general review of the constructions and biomedical applications of hydrogels from the viewpoint of swelling-shrinkable properties. Therefore, this review summarizes the tactics employed so far in tailoring the swelling-shrinkable properties of hydrogels and their biomedical applications. And a relatively comprehensive understanding of the current progress and future challenge of the hydrogels with different swelling-shrinkable features is provided for potential clinical translations.

Functional preference of the left inferior parietal lobule to second language reading.

Additional neural substance for reading in a second language has been reported by prior studies. However, to date, there has been little investigation into whether and how the brain's adaptation to a second language is induced by specific linguistic tasks or is a general effect during reading in a new language. To address this issue, our study investigated Chinese children learning English as a second language by combining cross-sectional and longitudinal Functional Magnetic Resonance Imaging (fMRI) studies. We compared brain activation across four reading tasks, orthographic tasks and phonological tasks in Chinese (the first language, L1) and English (the second language, L2). By comparing the activation pattern across languages, we observed greater activation in the left inferior parietal lobule (LIPL) in English compared to Chinese, suggesting a functional preference of the LIPL to L2. In addition, greater correlation between LIPL-related FC and L2 was mainly observed in the phonological task, indicating that LIPL could be associated with phonological processing. Moreover, a proportion of the children were enrolled in an 8-week phonological-based reading-training program. We observed significant functional plasticity of the LIPL elicited by this training program only in the English phonological task and not in the orthographic task, further substantiating that the additional requirements of the LIPL in L2 are mainly associated with phonological processing. The findings provide new insights into understanding the functional contribution of the LIPL to reading in a second language.

Collagen-Based Biomaterials for Tissue Engineering.

Collagen is commonly used as a regenerative biomaterial due to its excellent biocompatibility and wide distribution in tissues. Different kinds of hybridization or cross-links are favored to offer improvements to satisfy various needs of biomedical applications. Previous reviews have been made to introduce the sources and structures of collagen. In addition, biological and mechanical properties of collagen-based biomaterials, their modification and application forms, and their interactions with host tissues are pinpointed. However, there is still no review about collagen-based biomaterials for tissue engineering. Therefore, we aim to summarize and discuss the progress of collagen-based materials for tissue regeneration applications in this review. We focus on the utilization of collagen-based biomaterials for bones, cartilages, skin, dental, neuron, cornea, and urological applications and hope these experiences and outcomes can provide inspiration and practical techniques for the future development of collagen-based biomaterials in related application fields. Moreover, future improving directions and challenges for collagen-based biomaterials are proposed as well.

NLRP3 inflammasome activation in cigarette smoke priming for Pseudomonas aeruginosa-induced acute lung injury.

It is increasingly recognized that cigarette smoke (CS) exposure increases the incidence and severity of acute respiratory distress syndrome (ARDS) in critical ill humans and animals. However, the mechanism(s) is not well understood. This study aims to investigate mechanism underlying the priming effect of CS on Pseudomonas aeruginosa-triggered acute lung injury, by using pre-clinic animal models and genetically modified mice. We demonstrated that CS impaired P. aeruginosa-induced mitophagy flux, promoted p62 accumulation, and exacerbated P. aeruginosa-triggered mitochondrial damage and NLRP3 inflammasome activation in alveolar macrophages; an effect associated with increased acute lung injury and mortality. Pharmacological inhibition of caspase-1, a component of inflammasome, attenuated CS primed P. aeruginosa-triggered acute lung injury and improved animal survival. Global or myeloid-specific knockout of IL-1ß, a downstream component of inflammasome activation, also attenuated CS primed P. aeruginosa-triggered acute lung injury. Our results suggest that NLRP3 inflammasome activation is an important mechanism for CS primed P. aeruginosa-triggered acute lung injury. (total words: 155).

Shear-thinning and self-healing chitosan-graphene oxide hydrogel for hemostasis and wound healing.

Hydrogels with injectability, self-healing ability and adhesiveness have great potential for hemostasis and full-thickness skin wound repair, which are usually fabricated by multistep chemical synthesis and the use of organic solvents and catalyst. Herein, we report an injectable and self-healing hydrogel facilely prepared through one-pot heating of chitosan and graphene oxide mixture solution, without any pollutant and waste generated. The dynamic reversible breakage and recombination of noncovalent bonds between chitosan and graphene oxide endows the hydrogel injectability and self-healing ability. In addition, the mechanical and rheological properties of the hydrogels can be controlled by varying the dosage of graphene oxide. Meanwhile, hydrogels exhibited good adhesiveness and hemocompatibility. Finally, in vivo experiments in a rat liver bleeding model and full-thickness skin defect model verified the outstanding hemostatic and wound healing capability of the hydrogels, indicating the promising future for use as wound dressing.

Peritumoral matrilin-2 staining may be useful in distinguishing basal cell carcinoma from folliculocentric basaloid proliferation.

BACKGROUND: Folliculocentric basaloid proliferation (FBP) is a benign and reactive proliferation which can histopathologically mimic basal cell carcinomas (BCCs). The incidental presence of FBP during the excision of a BCC can occasionally lead to excessive tissue removal. One distinguishing feature of BCCs is that they invade the stroma, whereas FBPs generally do not. METHODS: Matrilin-2 is an extracellular matrix protein associated with tumor invasion, and we compared the expression of matrilin-2 in peritumoral cells of BCC and FBP. RESULTS: We found increased matrilin-2 expression within the peritumoral stroma of 41 of 42 BCCs (97.7%), with strong expression in all (100%) cases of infiltrative subtypes and in 21 of 25 (84%) nodular subtypes of BCC. We found no expression of peritumoral matrilin-2 in any of the seven cases of FBP. CONCLUSION: Our results suggest that immunolabeling with the matrilin-2 antibody may help distinguish BCCs from FBPs.

Biomedical applications of chitosan-graphene oxide nanocomposites.

Chitosan (CS) and graphene oxide (GO) nanocomposites have received wide attention in biomedical fields due to the synergistic effect between CS which has excellent biological characteristics and GO which owns great physicochemical, mechanical, and optical properties. Nanocomposites based on CS and GO can be fabricated into a variety of forms, such as nanoparticles, hydrogels, scaffolds, films, and nanofibers. Thanks to the ease of functionalization, the performance of these nanocomposites in different forms can be further improved by introducing other functional polymers, nanoparticles, or growth factors. With this background, the current review summarizes the latest developments of CS-GO nanocomposites in different forms and compositions in biomedical applications including drug and biomacromolecules delivery, wound healing, bone tissue engineering, and biosensors. Future improving directions and challenges for clinical practice are proposed as well.

Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?

Understanding of sterile inflammation and its associated biological triggers and diseases is still at the elementary stage. This becomes more warranted in cases where infections are not associated with the pathology. Detrimental effects of bacterial and viral infections on the immune responses at the maternal-fetal interface as well as pregnancy outcomes have been well documented. However, an infection-induced etiology is not thought to be a major contributing component to severe pregnancy complications such as preeclampsia (PE) and gestational diabetes. How is then an inflammatory signal thought to be associated with these pregnancy complications? It is not clear what type of inflammation is involved in the onset of PE-like features. We opine that sterile inflammation regulated by the inflammasome-gasdermins-caspase-1 axis is a contributory factor to the onset of PE. We hypothesize that increased production and release of damage-associated molecular patterns (DAMPs) or Alarmins such as high-mobility group box1 (HMGB1), cell-free fetal DNA, uric acid, the NOD-like receptor pyrin-containing receptor 3 (NLRP3) inflammasome, IL-1ß and IL-18 occur in the PE placenta. Some of these molecules have already been observed in the placenta from women with PE. Mechanistically, emerging evidence has demonstrated that excessive placental endoplasmic reticulum (ER) stress, impaired autophagy and gasdermine D (GSDMD)-mediated intrinsic pyroptosis are key events that contribute to systemic sterile inflammation in patients with PE, especially early-onset PE (e-PE). In this review, we highlight the advances on the roles of sterile inflammation and inflammatory signaling cascades involving ER stress, autophagy deficiency and pyroptosis in PE pathophysiology. Deciphering the mechanisms underlying these inflammatory pathways may provide potential diagnostic biomarkers and facilitate the development of therapeutic strategies to treat this devastating disease.

Fabrication and applications of bioactive chitosan-based organic-inorganic hybrid materials: A review.

Organic-inorganic hybrid materials like bone, shells, and teeth can be found in nature, which are usually composed of biomacromolecules and nanoscale inorganic ingredients. Synergy of organic-inorganic components in hybrid materials render them outstanding and versatile performance. Chitosan is commonly used organic materials in bionic hybrid materials since its bioactive properties and could be controllable tailored by various means to meet complex conditions in different applications. Among these fabrication means, hybridization was favored for its convenience and efficiency. This review discusses three kinds of chitosan-based hybrid materials: hybridized with hydroxyapatite, calcium carbonate, and clay respectively, which are the representative of phosphate, carbonate, and hydrous aluminosilicates. Here, we reported the latest developments of the preparation methods, composition, structure and applications of these bioactive hybrid materials, especially in the biomedical field. Despite the great progress was made in bioactive organic-inorganic hybrid materials based on chitosan, some challenges and specific directions are still proposed for future development in this review.

Histone deacetylases in modulating cardiac disease and their clinical translational and therapeutic implications.

Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. Histone deacetylases (HDACs) play an important role in the epigenetic regulation of genetic transcription in response to stress or pathological conditions. HDACs interact with a complex co-regulatory network of transcriptional regulators, deacetylate histones or non-histone proteins, and modulate gene expression in the heart. The selective HDAC inhibitors have been considered to be a critical target for the treatment of cardiac disease, especially for ameliorating cardiac dysfunction. In this review, we discuss our current knowledge of the cellular and molecular basis of HDACs in mediating cardiac development and hypertrophy and related pharmacologic interventions in heart disease.

Mitochondrial Fission Mediated Cigarette Smoke-induced Pulmonary Endothelial Injury.

Cigarette smoke (CS) exposure increases the risk for acute respiratory distress syndrome in humans and promotes alveolar-capillary barrier permeability and acute lung injury in animal models. However, the underlying mechanisms are not well understood. Mitochondrial fusion and fission are essential for mitochondrial homeostasis in health and disease. In this study, we hypothesized that CS caused endothelial injury via an imbalance of mitochondrial fusion and fission and resultant mitochondrial oxidative stress and dysfunction. We noted that CS altered mitochondrial morphology by shortening mitochondrial networks and causing perinuclear accumulation of damaged mitochondria in primary rat lung microvascular endothelial cells. We also found that CS increased mitochondrial fission likely by decreasing Drp1-S637 and increasing FIS1, Drp1-S616 phosphorylation, mitochondrial translocation, and tetramerization and reduced mitochondrial fusion likely by decreasing Mfn2 in lung microvascular endothelial cells and mouse lungs. CS also caused aberrant mitophagy, increased mitochondrial oxidative stress, and reduced mitochondrial respiration. An inhibitor of mitochondrial fission and a mitochondria-specific antioxidant prevented CS-induced increased endothelial barrier dysfunction and apoptosis. Our data suggest that excessive mitochondrial fission and resultant oxidative stress are essential mediators of CS-induced endothelial injury and that inhibition of mitochondrial fission and mitochondria-specific antioxidants may be useful therapeutic strategies for CS-induced endothelial injury and associated pulmonary diseases.

The important role of histone deacetylases in modulating vascular physiology and arteriosclerosis.

Cardiovascular diseases are the leading cause of deaths in the world. Endothelial dysfunction followed by inflammation of the vessel wall leads to atherosclerotic lesion formation that causes ischemic heart and myocardial hypertrophy, which ultimately progress into cardiac dysfunction and failure. Histone deacetylases (HDACs) have been recognized to play crucial roles in cardiovascular disease, particularly in the epigenetic regulation of gene transcription in response to a variety of stresses. The unique nature of HDAC regulation includes that HDACs form a complex co-regulatory network with other transcription factors, deacetylate histones and non-histone proteins to facilitate the regulatory mechanism of the vascular system. The selective HDAC inhibitors are considered as the most promising target in cardiovascular disease, especially for preventing cardiac hypertrophy. In this review, we discuss our present knowledge of the cellular and molecular basis of HDACs in mediating the biological function of vascular cells and related pharmacologic interventions in vascular disease.

Sugar-Based Aggregation-Induced Emission Luminogens: Design, Structures, and Applications.

Sugars are abundant natural sources existing in biological systems, and bioactive saccharides have attracted much more attention in the field of biochemistry and biomaterials. For better understanding of the sugar-based biomaterials and biological sciences, aggregation-induced emission luminogens (AIE-gens) have been widely employed for detection, tracing, and imaging. This review covers the applications of AIE molecules on sugar-based biomaterials by three parts, polysaccharide, oligosaccharide, and monosaccharide, mainly focusing on saccharide detection, stimuli response materials preparation, bioimaging, and study of the AIE mechanism. These excellent works suggest the promising future of the sugar-based AIE bioconjugates, considering that the naturally designed and elaborately functionalized saccharides play discriminate roles in biological processes and AIE-tagged species may work as an indicator in each case. However, there are a lot of sugar-based biological species that have not been touched, such as mucopolysaccharides and glycoproteins on the cell surface and in the cell plasma. Based on these features, we enthusiastically look forward to more glorious developments in this bright research area.

Blockade of equilibrative nucleoside transporter 1/2 protects against Pseudomonas aeruginosa-induced acute lung injury and NLRP3 inflammasome activation.

Pseudomonas aeruginosa infections are increasingly multidrug resistant and cause healthcare-associated pneumonia, a major risk factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Adenosine is a signaling nucleoside with potential opposing effects; adenosine can either protect against acute lung injury via adenosine receptors or cause lung injury via adenosine receptors or equilibrative nucleoside transporter (ENT)-dependent intracellular adenosine uptake. We hypothesized that blockade of intracellular adenosine uptake by inhibition of ENT1/2 would increase adenosine receptor signaling and protect against P. aeruginosa-induced acute lung injury. We observed that P. aeruginosa (strain: PA103) infection induced acute lung injury in C57BL/6 mice in a dose- and time-dependent manner. Using ENT1/2 pharmacological inhibitor, nitrobenzylthioinosine (NBTI), and ENT1-null mice, we demonstrated that ENT blockade elevated lung adenosine levels and significantly attenuated P. aeruginosa-induced acute lung injury, as assessed by lung wet-to-dry weight ratio, BAL protein levels, BAL inflammatory cell counts, pro-inflammatory cytokines, and pulmonary function (total lung volume, static lung compliance, tissue damping, and tissue elastance). Using both agonists and antagonists directed against adenosine receptors A2AR and A2BR, we further demonstrated that ENT1/2 blockade protected against P. aeruginosa -induced acute lung injury via activation of A2AR and A2BR. Additionally, ENT1/2 chemical inhibition and ENT1 knockout prevented P. aeruginosa-induced lung NLRP3 inflammasome activation. Finally, inhibition of inflammasome prevented P. aeruginosa-induced acute lung injury. Our results suggest that targeting ENT1/2 and NLRP3 inflammasome may be novel strategies for prevention and treatment of P. aeruginosa-induced pneumonia and subsequent ARDS.

Cationic quaternized chitosan bioconjugates with aggregation-induced emission features for cell imaging.

Fluorescent bioprobs are in urgent demand to monitor important biological events in biomedicine. However, the aggregation-caused quenching character, high toxicity, water-insolubility and easy leakage property of conventional small molecular dyes hinder the development in this area. In this work, an aggregation-induced emission (AIE) bioconjugate was synthesised by labeling tetraphenylethylene (TPE) to quaternized chitosan (QCS). The TPE-QCS bioconjugate emits strong fluorescence even in solid state, and is cationic and water-soluble over a wide range of pH values. The TPE-QCS aqueous solution stained HeLa cells by dose- and time-depent manner and imaged living cells with bright fluorescence. Futhermore, the cationic bioconjugate was readily internalized by cells through endocytosis, and further aggragated to large sizes and adhered to negatively charged organelle membranes inside cells achieving fluorescent cell imaging with fluorescence enhancement and leakage-free staining. The AIE-active TPE-QCS with cationic nature, good water-solubility over a wide pH range and unique cell imaging properties could trace HeLa cells for as long as 23 passages, that was obviously superior to existing commercial cellular tracer, so has promising application prospects as ultra long-term tracer in biomedical field.

Inhibition of GATA2 restrains cell proliferation and enhances apoptosis and chemotherapy mediated apoptosis in human GATA2 overexpressing AML cells.

GATA2, a zinc finger transcription factor predominantly expressed in hematopoietic cells, acts as an essential regulator of hematopoietic stem cell generation, survival and functionality. Loss and gain of GATA2 expression has been implicated in myelodysplastic syndrome and acute myeloid leukemia (AML) yet the precise biological impact of GATA2 expression on human AML cell fate decisions remains ambiguous. Herein, we performed large-scale bioinformatics that demonstrated relatively frequent GATA2 overexpression in AML patients as well as select human AML (or AML-like) cell lines. By using shRNAi to target GATA2 in these AML cell lines, and an AML cell line expressing normal levels of GATA2, we found that inhibition of GATA2 caused attenuated cell proliferation and enhanced apoptosis exclusively in AML cell lines that overexpress GATA2. We proceeded to pharmacologically inhibit GATA2 in concert with AML chemotherapeutics and found this augmented cell killing in AML cell lines that overexpress GATA2, but not in an AML cell line expressing normal levels of GATA2. These data indicate that inhibition of GATA2 enhances chemotherapy-mediated apoptosis in human AML cells overexpressing GATA2. Thus, we define novel insights into the oncogenic role of GATA2 in human AML cells and suggest the potential utilization of transient GATA2 therapeutic targeting in AML.

High strength graphene oxide/chitosan composite screws with a steel-concrete structure.

Due to the biocompatibility, biodegradability and numerous resources of chitosan (CS), CS screws attract much more attention, as a new generation of internal fixation devices. Herein, a facile solution-casting method was utilized to fabricate CS composite screws with a steel-concrete structure by combining graphene oxide (GO) and CS fiber bundles. The embedding GO endowed CS screws with a Honeycomb-Cobweb network. And CS screws reinforced with CS fiber bundles of four arrangement sequences could endure different degrees of external force. The optimal arrangement type of CS fiber bundles (the linear type) and addition amount of GO (0.15 wt%) was utilized to construct the steel-concrete structure. Due to the mechanical interlocking between the GO/CS matrices and CS fiber bundles, the bending strength of CS composite screws, with such an unusual structure, could reach high up to 378 MPa, approximately 1.88 times the blank control group was. The findings stand out as a new tool to prepare high bending strength screws and the steel-concrete structure might be used effectively in more critical load-bearing situations.

Highly mineralized chitosan-based material with large size, gradient mineral distribution and hierarchical structure.

Nature materials constituted with organic and inorganic components have hierarchical structure and superior performance. Although a variety of techniques have been developed to mimic microstructure and properties of natural mineralized materials, facile and rapid fabrication of large-size bulk materials with high calcium content under ambient conditions still remains a major challenge. Here, we present a feasible and versatile route to a highly mineralized material with an in situ preparation method where gelation and mineralization occur simultaneously. Meanwhile, hierarchically ordered hydrogel microstructures are formed during the gelation, and controllable inorganic gradient distribution forms along with mineralization spontaneously. With the achievement of high mineral content by the assistance of urea, this fabrication route is facile and efficient, only taking several hours to complete the gelation and mineralization, and large-scale materials are prepared readily. This chitosan matrix-directed mineralization represents a rational and promising strategy for fast fabrication of highly mineralized material with hierarchical structure on a large scale, and the chitosan-based mineralized material has great potential for applications in bone repairing and tissue engineering.