Doxycycline-loaded carboxymethyl cellulose/sodium alginate/gelatin hydrogel: An approach for enhancing pressure ulcer healing in a rat model.

Pressure ulcers, or bedsores, are created by areas of the skin under prolonged pressure and can lead to skin and underlying tissue damage. The present study evaluated the effects of carboxymethyl cellulose/sodium alginate/gelatin (CMC/Alg/Gel) hydrogel containing doxycycline (DOX) on improving the healing process of pressure ulcers. The magnet was used to apply pressure on the dorsum skin rat to induce a pressure ulcer model. Then sterile gauze, CMC/Alg/Gel, and CMC/Alg/Gel/1% w/v DOX hydrogels were used to cover the wounds. Blood compatibility, weight loss, cytocompatibility, drug release rate, cell viability, wound closure, and re-epithelialization were evaluated in all animals on the 14th day after treatment. In vivo results and histopathological evaluation showed 56.66% wound closure and the highest re-epithelialization in the CMC/Alg/Gel/1% w/v DOX hydrogel group (14 days after treatment). Furthermore, real-time PCR results indicated that the hydrogel containing DOX significantly decreased the expression of the MMP family consisting of MMP2 and MMP9 mRNA and also increased the expression of vascular endothelial growth factor VEGF mRNA. This study suggested that the addition of DOX, an antibiotic and MMP inhibitor, to hydrogels may be effective in the healing process of pressure ulcers.

Enhancing pressure ulcer healing and tissue regeneration by using N-acetyl-cysteine loaded carboxymethyl cellulose/gelatin/sodium alginate hydrogel.

Prolonged pressure on the skin can result in pressure ulcers, which may lead to serious complications, such as infection and tissue damage. In this study, we evaluated the effect of a carboxymethyl cellulose/gelatin/sodium alginate (CMC/Gel/Alg) hydrogel containing N-acetyl-cysteine (NAC) on the healing of pressure ulcers. Pressure ulcers were induced by applying a magnet to the dorsum of rat skin. The wounds were then treated with sterile gauze, ChitoHeal Gel®, and CMC/Gel/Alg hydrogel dressings with or without NAC for the other groups. We evaluated the morphology, weight loss, swelling, rheology, blood compatibility, cytocompatibility, antioxidant capacity, and wound scratch of the prepared hydrogel. MTT assay revealed that the optimum concentration of NAC was 5 mg/ml, which induced higher cell proliferation and viability. Results of the histopathological evaluation showed increased wound closure, and complete re-epithelialization in the hydrogel-containing NAC group compared to the other groups. The CMC/Gel/Alg/5 mg/ml NAC hydrogel dressing showed 84% wound closure at 14 days after treatment. Immunohistochemical results showed a decrease in the level of TNF-α on day 14 compared day 7. Results of the qPCR assay revealed that NAC hydrogel increased the expression of Collagen type I and TGF-ß1 and decreased MMP2 and MMP9 mRNA on the 14th day. The results suggest that the CMC/Gel/Alg/5 mg/ml NAC hydrogel with antioxidant properties is an appropriate dressing for wound healing.

Evaluating the antibacterial effect of meropenem-loaded chitosan/sodium tripolyphosphate (TPP) nanoparticles on Acinetobacter baumannii isolated from hospitalized patients.

BACKGROUND: Acinetobacter baumannii is a health threat due to its antibiotic resistance. Herein, antibiotic susceptibility and its association with the Toxin-antitoxin (TA) system genes in A. baumannii clinical isolates from Iran were investigated. Next, we prepared meropenem-loaded chitosan nanoparticles (MP-CS) and investigated their antibacterial effects against meropenem-susceptible bacterial isolates. METHODS: Out of 240 clinical specimens, 60 A. baumannii isolates were assessed. Antibiotic resistance of the isolates against conventional antibiotics was determined alongside investigating the presence of three TA system genes (mazEF, relBE, and higBA). Chitosan nanoparticles were characterized in terms of size, zeta potential, encapsulation efficiency, and meropenem release activity. Their antibacterial effects were assessed using the well diffusion method, minimum inhibitory concentration (MIC), and colony-forming unit (CFU) counting. Their cytotoxic effects and biocompatibility index were determined via the MTT, LDH, and ROS formation assays. RESULTS: Ampicillin, ceftazidime, and colistin were the least effective, and amikacin and tobramycin were the most effective antibiotics. Out of the 60 isolates, 10 (16.7%), 5 (8.3%), and 45 (75%) were multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR), respectively. TA system genes had no significant effect on antibiotic resistance. MP-CS nanoparticles demonstrated an average size of 191.5 and zeta potential of 27.3 mV alongside a maximum encapsulation efficiency of 88.32% and release rate of 69.57%. MP-CS nanoparticles mediated similar antibacterial effects, as compared with free meropenem, against the A. baumannii isolates with significantly lower levels of meropenem. MP-CS nanoparticles remarkably prevented A549 and NCI-H292 cell infection by the A. baumannii isolates alongside demonstrating a favorable biocompatibility index. CONCLUSION: Antibiotic-loaded nanoparticles should be further designed and investigated to increase their antibacterial effect against A. baumannii and assess their safety and applicability in vivo settings.

Isolation and Characterization of Extracellular Vesicles of Chick Embryo Blood.

Exosomes from plants or animals are a cheap, available, and promising option in medicine, which can be used for the detection or treatment of various diseases. This study aims to evaluate the antitoxic and antioxidant properties of Extracellular vesicle (EVs) extracted from chicken embryo blood using a fibroblast cell line (NIH/3T3). EVs from chick embryos were extracted in this experimental investigation using the sedimentation method and examined using dynamic light scattering (DLS) and field emission electron microscopy (FE-SEM). The protein concentration and overall antioxidant capacity of the EVs were determined using bicinchoninic acid (BCA) and antioxidant capacity (FRAP). EVs were added to NIH/3T3 cells at varying concentrations (1, 2, and 10 mg/ml), and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay test was used to measure cell survival. The size of the isolated EVs was confirmed to be less than 100 nm by electron microscopy and DLS. The quantity of protein in these EVs was 3200 µg/ml, and their total antioxidant capacities were 3130.17, 1914.122, and 976.9 µMol/L. The MTT test findings demonstrated that NIH/3T3 cells survived treatment with EVs (P ≤ 0.001) compared to the control group. Antioxidant-rich and protein-rich exosomes in chicken embryos may be valuable in managing oxidative stress.

Polysilsesquioxane decorated ZIF-8 as a potential pH-responsive vehicle for topical delivery and release of acyclovir and tetracycline: Investigation of blood compatibility, cytotoxicity and antibacterial properties.

In this research, poly-chloropropylmethyl-silsesquioxanen was prepared and decorated with ZIF-8 in order to investigate its loading capacity for acyclovir and tetracycline. Before and after drug loadings, the composites were characterized by FT-IR, SEM-EDS, XRD, and XPS analyses. Then, the in-vitro release of these drugs was investigated by UV-Vis spectroscopy in different buffers (pH = 5, 7.4, and 9.1). The results showed that the release of ACV reached a maximum amount of 41.3 mg at pH = 7.4 during 12 h. In comparison, the release of TC reached a maximum amount of 22.5 mg at pH = 5 during 6 h. The blood compatibility, in-vitro cytotoxicity on the L929 fibroblast cells line, and antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa were also investigated for this composite as a drug carrier.

Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics.

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches.

Assessment of the ability of Pseudomonas aeruginosa and Staphylococcus aureus to create biofilms during wound healing in a rat model treated with carboxymethyl cellulose/carboxymethyl chitosan hydrogel containing EDTA.

The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic acid (EDTA) as the materials for wound healing. CMC and CMCS solutions were prepared with a concentration of 4% (w/v). These solutions were made using normal saline serum with a concentration of 0.5% (v/v). Additionally, EDTA with the concentrations of 0.01%, 0.05%, 0.1%, 0.5%, 1%, and 2% (w/v) was included in the prepared polymer solution. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with average in size 88.71 ± 5.93 µm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. The antibacterial experiments showed that the formulated CMC/CMCS/EDTA 0.5% hydrogel inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, the produced hydrogels were haemocompatible and biocompatible. At the last stage, the evaluation of wound healing in the animal model demonstrated that the use of the produced hydrogels significantly improved the process of wound healing. Finally, the findings substantiated the effectiveness of the formulated hydrogels as the materials for promoting wound healing and antibacterial agents.

Assessing the efficacy of curcumin-loaded alginate hydrogel on skin wound healing: A gene expression analysis.

Skin tissue engineering has gained significant attention as a promising alternative to traditional treatments for skin injuries. In this study, we developed 3D hydrogel-based scaffolds, Alginate, incorporating different concentrations of Curcumin and evaluated their properties, including morphology, swelling behavior, weight loss, as well as hemo- and cytocompatibility. Furthermore, we investigated the therapeutic potential of Alginate hydrogel containing different amounts of Curcumin using an in vitro wound healing model. The prepared hydrogels exhibited remarkable characteristics, SEM showed that the pore size of hydrogels was 134.64 µm with interconnected pores, making it conducive for cellular infiltration and nutrient exchange. Moreover, hydrogels demonstrated excellent biodegradability, losing 63.5% of its weight over 14 days. In addition, the prepared hydrogels had a stable release of curcumin for 3 days. The results also show the hemocompatibility of prepared hydrogels and a low amount of blood clotting. To assess the efficacy of the developed hydrogels, 3T3 fibroblast growth was examined during various incubation times. The results indicated that the inclusion of Curcumin at a concentration of 0.1 mg/mL positively influenced cellular behavior. The animal study showed that Alginate hydrogel containing 0.1 mg/mL curcumin had high wound closure(more than 80%) after 14 days. In addition, it showed up-regulation of essential wound healing genes, including TGFß1 and VEGF, promoting tissue repair and angiogenesis. Furthermore, the treated group exhibited down-regulation of MMP9 gene expression, indicating a reduction in matrix degradation and inflammation. The observed cellular responses and gene expression changes substantiate the therapeutic efficacy of prepared hydrogels. Consequently, our study showed the healing effect of alginate-based hydrogel containing Curcumin on skin injuries.

Magnesium-oxide-enhanced bone regeneration: 3D-printing of gelatin-coated composite scaffolds with sustained Rosuvastatin release.

Critical-size bone defects are one of the main challenges in bone tissue regeneration that determines the need to use angiogenic and osteogenic agents. Rosuvastatin (RSV) is a class of cholesterol-lowering drugs with osteogenic potential. Magnesium oxide (MgO) is an angiogenesis component affecting apatite formation. This study aims to evaluate 3D-printed Polycaprolactone/ß-tricalcium phosphate/nano-hydroxyapatite/ MgO (PCL/ß-TCP/nHA/MgO) scaffolds as a carrier for MgO and RSV in bone regeneration. For this purpose, PCL/ß-TCP/nHA/MgO scaffolds were fabricated with a 3D-printing method and coated with gelatin and RSV. The biocompatibility and osteogenicity of scaffolds were examined with MTT, ALP, and Alizarin red staining. Finally, the scaffolds were implanted in a bone defect of rat's calvaria, and tissue regeneration was investigated after 3 months. Our results showed that the simultaneous presence of RSV and MgO improved biocompatibility, wettability, degradation rate, and ALP activity but decreased mechanical strength. PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds produced sustained release of MgO and RSV within 30 days. CT images showed that PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds filled approximately 86.83 + 4.9 % of the defects within 3 months and improved angiogenesis, woven bone, and osteogenic genes expression. These results indicate the potential of PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds as a promising tool for bone regeneration and clinical trials.

Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A.

A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.

Hydrogel-Based Skin Regeneration.

The skin is subject to damage from the surrounding environment. The repair of skin wounds can be very challenging due to several factors such as severe injuries, concomitant infections, or comorbidities such as diabetes. Different drugs and wound dressings have been used to treat skin wounds. Tissue engineering, a novel therapeutic approach, revolutionized the treatment and regeneration of challenging tissue damage. This field includes the use of synthetic and natural biomaterials that support the growth of tissues or organs outside the body. Accordingly, the demand for polymer-based therapeutic strategies for skin tissue defects is significantly increasing. Among the various 3D scaffolds used in tissue engineering, hydrogel scaffolds have gained special significance due to their unique properties such as natural mimicry of the extracellular matrix (ECM), moisture retention, porosity, biocompatibility, biodegradability, and biocompatibility properties. First, this article delineates the process of wound healing and conventional methods of treating wounds. It then presents an examination of the structure and manufacturing methods of hydrogels, followed by an analysis of their crucial characteristics in healing skin wounds and the most recent advancements in using hydrogel dressings for this purpose. Finally, it discusses the potential future advancements in hydrogel materials within the realm of wound healing.

Fabrication of Rosuvastatin-Incorporated Polycaprolactone -Gelatin Scaffold for Bone Repair: A Preliminary In Vitro Study.

OBJECTIVE: Rosuvastatin (RSV) is a hydrophilic, effective statin with a long half-life that stimulates bone regeneration. The present study aims to develop a new scaffold and controlled release system for RSV with favourable properties for bone tissue engineering (BTE). MATERIALS AND METHODS: In this experimental study, high porous polycaprolactone (PCL)-gelatin scaffolds that contained different concentrations of RSV (0 mg/10 ml, 0.1 mg/10 ml, 0.5 mg/10 ml, 2.5 mg/10 ml, 12.5 mg/10 ml, and 62.5 mg/10 ml) were fabricated by the thermally-induced phase separation (TIPS) method. Mechanical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), compressive strength, porosity, MTT, alkaline phosphatase (ALP) activity, water contact angle, degradation rate, pH alteration, blood clotting index (BCI), and hemocompatibility. RESULTS: SEM analysis confirmed that the porous structure of the scaffolds contained interconnected pores. FTIR results showed that the RSV structure was maintained during the scaffold's fabrication. RSV (up to 62.5 mg/10 ml) increased compressive strength (16.342 ± 1.79 MPa), wettability (70.2), and degradation rate of the scaffolds. Scaffolds that contained 2.5 mg/10 ml RSV had the best effect on the human umbilical cord mesenchymal stem cell (HUC-MSCs) survival, hemocompatibility, and BCI. As a sustained release system, only 31.68 ± 0.1% of RSV was released from the PCL-Gelatin-2.5 mg/10 ml RSV scaffold over 30 days. In addition, the results of ALP activity showed that RSV increased the osteogenic differentiation potential of the scaffolds. CONCLUSION: PCL-Gelatin-2.5 mg/10 ml RSV scaffolds have favorable mechanical, physical, and osteogenic properties for bone tissue and provide a favorable release system for RSV. They can mentioned as a a promising strategy for bone regeneration that should be further assessed in animals and clinical studies.

Therapeutic effect of 5-ASA and hesperidin-loaded chitosan/Eudragit® S100 nanoparticles as a pH-sensitive carrier for local targeted drug delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) is an idiopathic disease characterized by colonic mucosal tissue destruction secondary to an excessive immune response. We synthesized pH-sensitive cross-linked chitosan/Eudragit® S100 nanoparticles (EU S100/CS NPs) as carriers for 5-aminosalicylic acid (5-ASA) and hesperidin (HSP), then conducted in-vitro and in-vivo studies and evaluated the therapeutic effects. In-vitro analysis revealed that the 5-ASA-loaded EU S100/CS NPs and the HSP-loaded EU S100/CS NPs had smooth and curved surfaces and ranged in size between 250 and 300 nm, with a zeta potential of 32 to 34 mV. FTIR analysis demonstrated that the drugs were loaded on the nanoparticles without significant alterations. The loading capacity and encapsulation efficiency of loading 5-ASA onto EU S100/CS NPs were 25.13 % and 60.81 %, respectively. Regarding HSP, these values were 38.34 % and 77.84 %, respectively. Drug release did not occur in simulated gastric fluid (SGF), while a slow-release pattern was recorded for both drugs in simulated intestinal fluid (SIF). In-vivo macroscopic and histopathological examinations revealed that both NPs containing drugs significantly relieved the symptoms of acetic acid (AA)-induced UC in Wistar rats. We conclude that the synthesized pH-sensitive 5-ASA/EU S100/CS NPs and HSP/EU S100/CS NPs offer promise in treating UC.

Nanofibrous polycaprolactone/gelatin scaffold containing gold nanoparticles: Physicochemical and biological characterization for wound healing.

In this study, gold nanoparticles were loaded into poly (ε-caprolactone) (PCL)/gelatin nanofibrous matrices to fabricate a potential wound dressing. The mats were produced by electrospinning of PCL/gelatin solution supplemented with synthesized gold nanoparticles (200, 400 and 800 ppm). Prepared scaffolds were investigated regarding their chemical properties, morphology, mechanical properties, surface wettability, water-uptake capacity, water vapor permeability, porosity, blood compatibility, microbial penetration test and cellular response. In addition to in vivo study, a full-thickness excisional wound in a rat model was used to evaluate the healing effect of prepared scaffolds. Results showed appropriate mechanical properties and porosity of prepared scaffolds. With L929 cells, the PCL/gelatin scaffold containing 400 ppm gold nanoparticles demonstrated the greatest cell growth. In vivo results validated the favorable wound-healing benefits of the scaffold incorporating gold nanoparticles, which triggered wound healing compared to sterile gauze. Our results showed the capability of nanofibrous matrices containing gold nanoparticles for successful wound treatment.

Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering.

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

A novel hydrogel containing 4-methylcatechol for skin regeneration: in vitro and in vivo study.

Skin damages are usual physical injuries and different studies have been done to improve wound healing. Hydrogel due to its properties like a moist environment and cooling wound site is a good option for wound treatment. In this study, we evaluated the consequence of using alginate/chitosan hydrogel contained various dosages of 4-Methylcatechol (0, 0.1, 1% (W/W)) on wound healing. After hydrogel fabrication, different tests like SEM, swelling, release, weight loss, and hemo- and cytocompatibility were done to characterize fabricated hydrogels. Finally, the rat model was used to assess Alginate/Chitosan hydrogel's therapeutic function containing 0.1 and 1% of 4-Methylcatechol. The pore size of hydrogel was between 24.5 ± 9 and 62.1 ± 11.63 µm and about 90% of hydrogel was lost after 14 days in the weight loss test. Blood compatibility and MTT assay showed that hydrogels were nontoxic and improved cell proliferation. In vivo test showed that Alginate/Chitosan/0.1%4-Methylcatechol improved wound healing and the results were significantly better than the gauze-treated wound. Our results showed dose depending effect of 4-Methylcatechol on wound healing. This study shows the treatment effect of 4-Methylcatechol on wound healing and the possibility of using it for treating skin injuries.

Hydrogel nanocomposite based on alginate/zeolite for burn wound healing: In vitro and in vivo study.

Objectives: The main objective of the current assay was to evaluate the antibacterial and regenerative effects of hydrogel nanocomposite containing pure natural zeolite (clinoptilolite) integrated with alginate (Alg) as wound healing/dressing biomaterials. Materials and Methods: The zeolites were size excluded, characterized by SEM, DLS, XRD, FTIR, and XRF, and then integrated into Alg hydrogel followed by calcium chloride crosslinking. The Alg and alginate zeolite (Alg/Zeo) hydrogel was characterized by swelling and weight loss tests, also the antibacterial, hemocompatibility, and cell viability tests were performed. In animal studies, the burn wound was induced on the back of rats and treated with the following groups: control, Alg hydrogel, and Alg/Zeo hydrogel. Results: The results showed that the hydrodynamic diameter of zeolites was 367 ± 0.2 nm. Zeolites did not show any significant antibacterial effect, however, the hydrogel nanocomposite containing zeolite had proper swelling as well as hemocompatibility and no cytotoxicity was observed. Following the creation of a third-degree burn wound on the back of rats, the results indicated that the Alg hydrogel and Alg/Zeo nanocomposite accelerated the wound healing process compared with the control group. Re-epithelialization, granulation tissue thickness, collagenization, inflammatory cell recruitment, and angiogenesis level were not significantly different between Alg and Alg/Zeo nanocomposite. Conclusion: These findings revealed that although the incorporation of zeolites did not induce a significant beneficial effect in comparison with Alg hydrogel, using zeolite capacity in hydrogel for loading the antibiotics or other effective compounds can be considered a promising wound dressing.

pH-sensitive HPMCP-chitosan nanoparticles containing 5-aminosalicylic acid and berberine for oral colon delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

A Combination of Physical and Chemical Treatments Is More Effective in The Preparation of Acellular Uterine Scaffolds.

OBJECTIVE: Decellularized uterine scaffold, as a new achievement in tissue engineering, enables recellularization and regeneration of uterine tissues and supports pregnancy in a fashion comparable to the intact uterus. The acellular methods are methods preferred in many respects due to their similarity to normal tissue, so it is necessary to try to introduce an acellularization protocol with minimum disadvantages and maximum advantages. Therefore, this study aimed to compare different protocols to achieve the optimal uterus decellularization method for future in vitro and in vivo bioengineering experiments. MATERIALS AND METHODS: In this experimental study, rat uteri were decellularized by four different protocols (P) using sodium dodecyl sulfate (SDS), with different doses and time incubations (P1 and P2), SDS/Triton-X100 sequentially (P3), and a combination of physical (freeze/thaw) and chemical reagents (SDS/Triton X-100). The scaffolds were examined by histopathological staining, DNA quantification, MTT assay, blood compatibility assay, FESEM, and mechanical studies. RESULTS: Histology assessment showed that only in P4, cell residues were completely removed. Masson's trichrome staining demonstrated that in P3, collagen fibers were decreased; however, no damage was observed in the collagen bundles using other protocols. In indirect MTT assays, cell viabilities achieved by all used protocols were significantly higher than the native samples. The percentage of red blood cell (RBC) hemolysis in the presence of prepared scaffolds from all 4 protocols was less than 2%. The mechanical properties of none of the obtained scaffolds were significantly different from the native sample except for P3. CONCLUSION: Uteri decellularized with a combination of physical and chemical treatments (P4) was the most favorable treatment in our study with the complete removal of cell residue, preservation of the three-dimensional structure, complete removal of detergents, and preservation of the mechanical property of the scaffolds.

Exploring the Physicochemical, Electroactive, and Biodelivery Properties of Metal Nanoparticles on Peripheral Nerve Regeneration.

Despite the advances in the regeneration/rehabilitation field of damaged tissues, the functional recovery of peripheral nerves (PNs), especially in a long gap injury, is considered a great medical challenge. Recent progress in nanomedicine has provided great hope for PN regeneration through the strategy of controlling cell behavior by metal nanoparticles individually or loaded on scaffolds/conduits. Despite the confirmed toxicity of metal nanoparticles due to long-term accumulation in nontarget tissues, they play a role in the damaged PN regeneration based on the topography modification of scaffolds/conduits, enhancing neurotrophic factor secretion, the ion flow improvement, and the regulation of electrical signals. Determining the fate of neural progenitor cells would be a major achievement in PN regeneration, which seems to be achievable by metal nanoparticles through altering cell vital approaches and controlling their functions. Therefore, in this literature, an attempt was made to provide an overview of the effective activities of metal nanoparticles on the PN regeneration, until the vital clues of the PN regeneration and how they are changed by metal nanoparticles are revealed to the researcher.