Osteogenic effect and mechanism of IL-10 in diabetic rat jaw defect mode.

OBJECTIVE: The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. METHODS: Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. RESULTS: IL-10 induced expression of arginase 1, TGF-ß1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. CONCLUSIONS: IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.

Nitrogen-doped hydrochars from shrimp waste as visible-light photocatalysts: Roles of nitrogen species.

The increasing shrimp waste production has caused severe environmental problems. In this study, nitrogen-doped hydrochars (NDHCs) were facilely synthesized from shrimp waste and glucose by one-pot hydrothermal carbonization (HTC). The characterizations showed that NDHCs had large surface areas of up to 30.5 m2 g-1 with numerous functional groups on their porous surfaces. The nitrogen content (1.3-2.8%) and species distribution in NDHCs were associated with the amount of added glucose. These NDHCs were applied as visible-light-induced photocatalysts, and their photocatalytic performances were evaluated by methylene blue (MB) degradation. The removal rate of MB reached 88.9% after 1 h of visible light radiation by NDHC-1, which was 2.3 times higher than that of glucose-derived hydrochar (GHC). The mechanism study showed that the improved photoactivity of NDHCs was attributed to the increased adsorption capacity by porous surface and the promoted formation of hydroxyl radicals by synergistic effects of quaternary N and pyrrolic N during photocatalysis. This study offered a green approach to preparing tunable, efficient, and low-cost photocatalyst from waste biomass and insight into the photocatalytic mechanism of hydrochar materials.

Chitosan-Gated Fluorescent Mesoporous Silica Nanocarriers for the Real-Time Monitoring of Drug Release.

We have constructed a novel gated nanocarrier for the real-time monitoring of drug release, consisting of three parts: (i) mesoporous silica nanoparticles (MSNs) as the drug carrier, (ii) chitosan as the nanovalve to block and unlock the pores, and (iii) 1,8-naphthalimide fluorophore as a connecting arm and fluorescent signal source. In the absence of glutathione (GSH), the integrity of the system results in the formation of pores in a closed state and the sulfone would block the intramolecular charge transfer (ICT) process, leading to no fluorescence emission. However, the nucleophilic attack of GSH can cause the removal of the chitosan and recovery of ICT property, thus triggering drug release and green fluorescence emission. The results demonstrate that the change of GSH concentration in vivo or vitro would lead to a change in drug release as well as a concurrent change in fluorescence signal, which can expand the application of our gated nanocarrier for monitoring different drug release in real time.

A self-healing, robust adhesion, multiple stimuli-response hydrogel for flexible sensors.

Ionic hydrogels have great application potential in human index monitoring and wound treatment, such as in wearable sensors, wound dressings, and ionic skin. However, the design of a hydrogel achieving the synergistic characteristics of excellent mechanical properties, robust adhesion, and multiple stimuli-responses remains a critical challenge. Herein, by introducing negatively charged clay nanosheets, we report a smart ionic Gelatin/PAAm/Clay hydrogel (GPNs gel) with a high conductivity of 10.87 mS cm-1. The as-prepared gel exhibits excellent self-healing properties, robust adhesion (interfacial toughness of up to 485 J m-2 with pigskin), and multiple stimuli-responses driven by salt ions, pH, and stress. Based on this hydrogel, a capacitive sensor has also been designed, which provides linear responses over a wide range (applied pressure up to 2 kPa) and sensitively monitors human motion. In addition, the gel also displays good biocompatibility with human lung embryonic (MRC-5) cells. These characteristics demonstrate that the GPNs gel is an ideal candidate for developing flexible sensor devices.

Cell Growth Stimulation, Cell Cycle Alternation, and Anti-Apoptosis Effects of Bovine Bone Collagen Hydrolysates Derived Peptides on MC3T3-E1 Cells Ex Vivo.

Bovine bone collagen hydrolysates promote bone formation through regulating bone growth. However, the peptide sequences within these isolates have not been characterized. In this study, twenty-nine peptides from bovine bone collagen hydrolysates were purified and identified using nano-HPLC-MS-MS and Peak Studio analysis. HHGDQGAPGAVGPAGPRGPAGPSGPAGKDGR (Deamidation) and GPAGANGDRGEAGPAGPAGPAGPR (Deamidation) enhanced cell viability, inhibited apoptosis, and significantly altered the cell cycle of MC3T3-E1 osteoblast cells. These peptides were selected to perform molecular docking analysis to examine the mechanism underlying these bioactivities. Molecular docking analysis showed that these two peptides formed hydrophobic interactions and hydrogen bonds with epidermal growth factor receptor (EGFR) to activate the EGFR-signaling pathway, which may explain their bioactivity. These findings indicate that these and other similar peptides might be candidates for the treatment of osteoporosis.

Effect of Collagen Peptide, Alone and in Combination with Calcium Citrate, on Bone Loss in Tail-Suspended Rats.

Oral administration of bovine collagen peptide (CP) combined with calcium citrate (CC) has been found to inhibit bone loss in ovariectomized rats. However, the protective effects of CP and CP-CC against bone loss have not been investigated in a tail-suspension simulated microgravity (SMG) rat model. Adult Sprague-Dawley rats (n = 40) were randomly divided into five groups (n = 8): a control group with normal gravity, a SMG control group, and three SMG groups that underwent once-daily gastric gavage with CP (750 mg/kg body weight), CC (75 mg/kg body weight) or CP-CC (750 and 75 mg/kg body weight, respectively) for 28 days. After sacrifice, the femurs were analyzed by dual-energy X-ray absorptiometry, three-point bending mechanical tests, microcomputed tomography, and serum bone metabolic markers. Neither CP nor CP-CC treatment significantly inhibited bone loss in SMG rats, as assessed by dual-energy X-ray absorptiometry and three-point bending mechanical tests. However, both CP and CP-CC treatment were associated with partial prevention of the hind limb unloading-induced deterioration of bone microarchitecture, as demonstrated by improvements in trabecular number and trabecular separation. CP-CC treatment increased serum osteocalcin levels. Dietary supplementation with CP or CP-CC may represent an adjunct strategy to reduce the risk of fracture in astronauts.

Preparation of Electrospun Gelatin Mat with Incorporated Zinc Oxide/Graphene Oxide and Its Antibacterial Activity.

Current wound dressings have poor antimicrobial activities and are difficult to degrade. Therefore, biodegradable and antibacterial dressings are urgently needed. In this article, we used the hydrothermal method and side-by-side electrospinning technology to prepare a gelatin mat with incorporated zinc oxide/graphene oxide (ZnO/GO) nanocomposites. The resultant fibers were characterized by field emission environment scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). Results indicated that the gelatin fibers had good morphology, and ZnO/GO nanocomposites were uniformly dispersed on the fibers. The loss of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) viability were observed to more than 90% with the incorporation of ZnO/GO. The degradation process showed that the composite fibers completely degraded within 7 days and had good controllable degradation characteristics. This study demonstrated the potential applicability of ZnO/GO-gelatin mats with excellent antibacterial properties as wound dressing material.

3D plotting in the preparation of newberyite, struvite, and brushite porous scaffolds: using magnesium oxide as a starting material.

Calcium phosphate (CaP)-containing materials, such as hydroxyapatite and brushite, are well studied bone grafting materials owing to their similar chemical compositions to the mineral phase of natural bone and kidney calculi. In recent studies, magnesium phosphate (MgP)-containing compounds, such as newberyite and struvite, have shown promise as alternatives to CaP. However, the different ways in degradation and release of Mg2+ and Ca2+ ions in vitro may affect the biocompatibility of CaP and MgP-containing compounds. In the present paper, newberyite, struvite, and brushite 3D porous structures were constructed by 3D-plotting combining with a two-step cementation process, using magnesium oxide (MgO) as a starting material. Briefly, 3D porous green bodies fabricated by 3D-plotting were soaked in (NH4)2HPO4 solution to form semi-manufactured 3D porous structures. These structures were then soaked in different phosphate solutions to translate the structures into newberyite, struvite, and brushite porous scaffolds. Powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS) were used to characterize the phases, morphologies, and compositions of the 3D porous scaffolds. The porosity, compressive strength, in vitro degradation and cytotoxicity on MC3T3-E1 osteoblast cells were assessed as well. The results showed that extracts obtained from immersing scaffolds in alpha-modified essential media induced minimal cytotoxicity and the cells could be attached merely onto newberyite and brushite scaffolds. Newberyite and brushite scaffolds produced through our 3D-plotting and two-step cementation process showed the sustained in vitro degradation and excellent biocompatibility, which could be used as scaffolds for the bone tissue engineering.

Effect of hydrothermal carbonization on heavy metals in swine manure: Speciation, bioavailability and environmental risk.

The speciation, bioavailability and environmental risk of heavy metals (HMs) in the hydrochar derived from hydrothermal carbonization (HTC) of swine manure were investigated in this study. The results indicated that the majority of HMs originally in swine manure were retained in the hydrochar by HTC, and CaO addition substantially reduced the HMs concentration in the hydrochar. HTC especially CaO assisted HTC significantly promoted the HMs transformation from the bioavailable fraction to the relatively stable fraction, and thus decreased their environmental risk in the hydrochar. Moreover, the Toxicity Characteristic Leaching Procedure and diethylenetriamine pentaacetic acid test revealed that the leachability and plant-bioavailability of HMs in swine manure were greatly declined by HTC especially for HTC with 15% CaO addition. The present study suggested that HTC was an effective disposal approach for swine manure from the perspective of HMs immobilization, especially for CaO assisted HTC.

Environmentally Friendly Gelatin/ß-Cyclodextrin Composite Fiber Adsorbents for the Efficient Removal of Dyes from Wastewater.

In this paper, environmentally friendly gelatin/ß-cyclodextrin (ß-CD) composite fiber adsorbents prepared by electrospinning were used for the removal of dyes from wastewater. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and a universal materials tester were employed to characterize the internal structures, surface morphologies and mechanical strength of the composite fiber adsorbents. Additionally, the fiber was evaluated as an adsorbent for the removal of methylene blue (MB) from aqueous solution. The effects of the raw material ratio, pH, temperature, concentration and adsorption time were studied. The results show that the gelatin/ß-CD composite fiber adsorbents possess excellent mechanical strength and high adsorption efficiency for MB. The adsorption equilibrium and adsorption kinetics are well-described by the Langmuir isotherm model and the pseudo-second-order kinetic model, respectively. The theoretical maximum adsorption capacity is 47.4 mg·g-1. Additionally, after nine successive desorption-adsorption cycles, the removal rate is still over 70%. Moreover, the gelatin/ß-CD composite fiber adsorbents exhibit excellent adsorption capability for basic fuchsin, gentian violet, brilliant blue R and malachite green dyes. Therefore, owing to the characteristics of degradability, low cost and high-efficiency, the gelatin/ß-CD composite fiber can be used as an efficient adsorbent for the removal of dyes from wastewater.

The Preparation of Chitosan Oligosaccharide/Alginate Sodium/Gelatin Nanofibers by Spiral-Electrospinning.

A spiral-electrospinning was used to mass-produce gelatin nanofibers with a content of chitosan oligosaccharide (COS) and alginate sodium (AS). Multiple jets were observed to form on the edges of the helix slice-spinneret simultaneously. Important electrospinning parameters, such as concentration of COS/gelatin aqueous solution, rotational velocity of spinneret and spinning distance, were examined to investigate the electrospinnability of COS/gelatin solution and the morphology of COS/gelatin nanofiber membranes. Due to the poor miscibility between COS and AS, COS/AS/gelatin nanofiber membranes were obtained from COS/gelatin solution and AS/gelatin solution by mixing electrospinning with multi-spinnerets. The novel needleless electrospinning not only avoided the possibility of nozzle-clogging, but also prepared COS/AS/gelatin nanofibers on a large scale for a wide variety of applications.

Preliminary exploration of the anti-ovarian cancer activity of peptides derived from bovine bone collagen hydrolysate and its related mechanisms.

Ovarian cancer, a malignant tumor that poses a significant threat to women's health, has seen a rise in incidence, prompting the urgent need for more effective treatment. This study primarily aimed to explore the potential of bovine collagen peptides in inhibiting ovarian cancer. The investigation in this study began with the identification of 268 peptide sequences through LC-MS/MS, followed by a screening process using molecular docking techniques to identify potential peptides capable of binding to EGFR. Subsequently, a series of experiments were performed, demonstrating the inhibitory effects of the peptide GPAGADGDRGEAGPAGPAGPAGPR on the proliferation of ovarian cancer cells. Transcriptomic analysis further revealed that this peptide can regulate cholesterol metabolism in ovarian cancer cells. Finally, a combination of time-resolved fluorescence resonance energy transfer, isothermal titration calorimetry, molecular docking, and molecular dynamics simulations were utilized to validate the ability of this peptide to bind to the epidermal growth factor receptor (EGFR) and impede the binding of epidermal growth factor (EGF) and EGFR.

Decellularized Amnion Membrane Triggers Macrophage Polarization for Desired Host Immune Response.

Appropriate regulation of immunomodulatory responses, particularly acute inflammation involving macrophages, is crucial for the desired functionality of implants. Decellularized amnion membrane (DAM) is produced by removing cellular components and antigenicity, expected to reduce immunogenicity and the risk of inflammation. Despite the potential of DAM as biomaterial implants, few studies have investigated its specific effects on immunomodulation. Here, it is demonstrated that DAM can regulate macrophage-driven inflammatory response and potential mechanisms are investigated. In vitro results show that DAM significantly inhibits M1 polarization in LPS-induced macrophages by inhibiting Toll-like receptors (TLR) signaling pathway and TNF signaling pathway and promotes macrophage M2 polarization. Physical signals from the 3D micro-structure and the active protein, DCN, binding to key targets may play roles in the process. In the subcutaneous implant model in rats, DAM inhibits the persistence of inflammation and fibrous capsule formation, while promoting M2 macrophage polarization, thereby facilitating tissue regeneration. This study provides insights into DAM's effect and potential mechanisms on the balance of M1/M2 macrophage polarization in vitro and vivo, emphasizing the immunomodulation of ECM-based materials as promising implants.

Electrospun Nanofiber Scaffold for Skin Tissue Engineering: A Review.

Skin tissue engineering (STE) is widely regarded as an effective approach for skin regeneration. Several synthetic biomaterials utilized for STE have demonstrated favorable fibrillar characteristics, facilitating the regeneration of skin tissue at the site of injury, yet they have exhibited a lack of in situ degradation. Various types of skin regenerative materials, such as hydrogels, nanofiber scaffolds, and 3D-printing composite scaffolds, have recently emerged for use in STE. Electrospun nanofiber scaffolds possess distinct advantages, such as their wide availability, similarity to natural structures, and notable tissue regenerative capabilities, which have garnered the attention of researchers. Hence, electrospun nanofiber scaffolds may serve as innovative biological materials possessing the necessary characteristics and potential for use in tissue engineering. Recent research has demonstrated the potential of electrospun nanofiber scaffolds to facilitate regeneration of skin tissues. Nevertheless, there is a need to enhance the rapid degradation and limited mechanical properties of electrospun nanofiber scaffolds in order to strengthen their effectiveness in soft tissue engineering applications in clinical settings. This Review centers on advanced research into electrospun nanofiber scaffolds, encompassing preparation methods, materials, fundamental research, and preclinical applications in the field of science, technology, and engineering. The existing challenges and prospects of electrospun nanofiber scaffolds in STE are also addressed.

Gelatin-Based Hydrogel Functionalized with Dopamine and Layered Double Hydroxide for Wound Healing.

Hydrogels with adhesion properties and a wetted structure are promising alternatives to traditional wound dressing materials. The insufficiency of gelatin hydrogels in terms of their adhesive and mechanical strength limits their application in wound dressings. This work presents the design and preparation of a gelatin-based hydrogel functionalized with dopamine (DA) and layered double hydroxide (LDH). The combination of DA and LDH improves the hydrogel's adhesion properties in terms of interfacial adhesion and inner cohesion. Hydrogels with 8% DA and 4% LDH attained the highest adhesion strength of 266.5 kPa, which increased to 295.5 and 343.3 kPa after hydrophobically modifying the gelatin with octanoyl and decanoyl aldehydes, respectively. The gelatin-based hydrogels also demonstrated a macroporous structure, excellent biocompatibility, and a good anti-inflammatory effect. The developed hydrogels accelerated wound healing in Sprague Dawley rat skin full-thickness wound models.

Chlorogenic acid/carboxymethyl chitosan nanoparticle-assisted biomultifunctional hyaluronic acid-based hydrogel scaffolds for burn skin repair.

Burns are a prevalent type of injury worldwide, affecting tens of millions of people each year and significantly impacting the physical and psychological well-being of patients. Consequently, prompt treatment of burn wounds is imperative, with oxidative stress and excessive inflammation identified as primary factors contributing to delayed healing. In recent years, there has been growing interest in in situ crosslinked multifunctional hydrogels as a minimally invasive approach for personalized treatment delivery. To address these, a photocrosslinkable methacryloyl hyaluronic acid hydrogel scaffold embedded with chlorogenic acid/carboxymethyl chitosan nanoparticles (CGA/CMCS-HAMA, CCH), was developed for the treatment of burn wounds. The hydrogel prepared degraded by over 50 % by day 20, demonstrating stability and meeting the therapeutic requirements for burn wounds. Leveraging the extracellular matrix-like properties of HAMA and the antioxidant capabilities of CGA/CMCS NPs, this hydrogel demonstrates the ability to locally and continuously scavenge ROS and inhibit lipid peroxidation, inhibiting ferroptosis. Moreover, hydrogels well modulate the expression of macrophage- and fibroblast-associated inflammatory factors. Additionally, the hydrogel promotes cell adhesion and migration, further supporting the healing process. Overall, this innovative approach offers a safe and promising solution for burn wound treatment, addressing drug breakthrough and safety concerns while being adaptable to various irregular wound types.

[Effect of Collagen Peptides on Function of Mouse T Lymphocytes under Simulated Microgravity].

OBJECTIVE: To understand the effect of collagen peptides on the function of mouse lymphocytes under simulated microgravity. METHODS: The splenocytes of mice were isolated, and the rotary cell culture system was used to simulate the microgravity. The T lymphocytes were stimulated with mitotic agents, concanavalin A (ConA), and the cells were treated with different concentrations of collagen peptides. The proliferation of lymphocytes and the levels of cytokines in the supernatant were detected. RESULTS: Simulated microgravity could inhibit the proliferation of spleen T lymphocytes and decrease the level of cytokines in the supernatant. Collagen peptides could promote the lymphocyte proliferation and cytokine production in cells cultured under simulated microgravity. CONCLUSION: Collagen peptides may attenuate the inhibitory effect of simulated microgravity on T lymphocytes by regulating the cell proliferation and the secretion of cytokines.

Identification and Characterization of Peptides from Bovine Collagen Hydrolysates that Promote Myogenic Cell Proliferation.

In this study, bovine collagen hydrolysate was purified via a series of chromatograms, and the peptides with the highest activity for promoting myoblast proliferation were identified by LC-MS-MS. It was demonstrated that the peptide GDAGPPGPAGPAGPPGPIG (hydroxylation) could promote C2C12 proliferation (+18.5% ± 0.04, P < 0.05). The certain peptide was capable of regulating the myogenic cell cycle and inhibiting myogenic cell apoptosis. By combining molecular docking, quantitative real-time PCR, and metabonomics, we suggested that the peptide GDAGPPGPAGPAGPPGPIG (hydroxylation) might bind to FGFR1 and affect the expression of genes downstream of FGFR1 and influence protein synthesis to promote myoblast proliferation. The above results showed that the peptides isolated in this study have the potential to alleviate sarcopenia in the elderly.

Preparation and identification of novel antioxidant peptides from camel bone protein.

Collagen hydrolysates are a vital source of bioactive peptides. The objective of this study was to prepare camel bone collagen hydrolysates with antioxidant activity, and to identify the peptides responsible for the antioxidant activity. To this end, single-factor and orthogonal tests were performed to explore the optimum preparation conditions. A hydrolysis time of 5 h, enzyme:substrate ratio of 1200 U/g, pH of 7.0, and a material:water ratio of 1:3.0 were adopted. Subsequently, the hydrolysates were purified using a series of chromatography procedures, and three novel peptides, GPPGPPGPPGPPGPPSGGFDF (hydroxylation), PATGDLTDFLK, and GSPGPQGPPGSIGPQ, possessing antioxidant abilities, were identified from the fraction using liquid chromatography-tandem mass spectrometry. The peptide PATGDLTDFLK showed excellent DPPH scavenging activity (39%) and a good cytoprotective effect on H2O2-induced oxidative stress damage in HepG2 cells with a 21.1% increase observed.

In situ self-assembly of polydopamine inside injectable hydrogels: antibacterial activity and photothermal therapy for superbug-infected wound healing.

Inspired by the mussel foot proteins, polydopamine nanoparticles (PDA NPs) are often used to design hydrogel wound dressings due to their strong wet adhesion. However, additional antibiotics or nanometal bactericides are always required to enhance their poor antibacterial activity, which will cause drug resistance and toxic side effects. Herein, self-assembly confined PDA NPs (SC-PDA NPs, <50 nm) are employed as a freestanding antibacterial ingredient for constructing an ideal hydrogel wound dressing, which maintains relatively strong reducibility and size effect. Through a rapid gelation (within 10 s) strategy triggered by electrostatic complexation, an antibacterial hydrogel system is obtained, in which the in situ self-assembly of the SC-PDA NPs continues, endowing the gel with outstanding antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA, >99.9%). With the continuous in situ self-assembly, the size of the PDA NPs increases (>200 nm), eventually giving the gel an efficient photothermal therapy effect. Moreover, the gel presents a relatively strong wet adhesion (63 kPa), superior biocompatibility and non-immunogenicity. This work offers innovative insights into the antibacterial mechanism of SC-PDA NPs and provides a novel design for constructing safe antibacterial hydrogel wound dressings, demonstrating great potential applications in superbug-infected wound healing.