Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair.

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.

Investigating layer-by-layer chitosan-dextran sulfate-coated mesoporous silica as a pH-sensitive drug delivery system.

Mesoporous silica nanoparticles (MSNPs) coated by chitosan (CS) were shown to be a proper candidate as a carrier for drug delivery purposes. However, choosing the suitable drug-containing complexes to be applied on MSNPs-CS is of much greater importance to evaluate the possible candidate for an efficient combination of cell viability, drug release kinetics, and atherosclerosis prevention. In this regard, this study concentrates on the synthesis and assessment of coated MSNPs-CS designed for drug delivery purposes. The MSNPs are coated with polyelectrolyte complexes (PEC) composed of CS and dextran sulfate (MSNPs-CS-DX), serving as a versatile drug carrier with favorable biological characteristics. CS-DX is applied to MSNPs without requiring complex or multi-step synthesis procedures. Rosuvastatin, a cholesterol-lowering medication, is chosen for its therapeutic relevance. Additionally, CS-DX is found to relatively impede the uptake of low-density lipoproteins (LDLs) by macrophages, enhancing their potential therapeutic utility. FTIR pattern, FESEM, and TEM images prove MSNPs-CS-DX formation. DLS measurement demonstrates the average particle size of 110 nm for MSNPs, with the combined thickness of CS and DX layers ranging from 10 to 15 nm. BET test is carried out to evaluate the pore size and porosity of structure, showing outstanding results that cause an entrapment efficiency of 57% for MSNPs-CS-DX. Furthermore, the findings demonstrate the pH sensitivity of MSNPs-CS-DX on drug release kinetics. Notably, the CS-DX layer exhibits a significant enhancement in cell viability of human umbilical vein endothelial cells (HUVEC) by approximately 24% within a 24 h timeframe compared to MSNPs lacking CS-DX.

Engineering Wet-Resistant and Osteogenic Nanocomposite Adhesive to Control Bleeding and Infection after Median Sternotomy.

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.

MRI tracking of human Wharton's jelly stem cells seeded onto acellular dermal matrix labeled with superparamagnetic iron oxide nanoparticles in burn wounds.

Background: In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies. This study investigated tracking of human Wharton's jelly stem cells (hWJSCs) seeded onto an acellular dermal matrix (ADM) and labeled with superparamagnetic iron oxide nanoparticles (SPIONs) by magnetic resonance imaging (MRI) in burn injury. Method: The hWJSCs were characterized and assessed for growth kinetics. A total of 30 rats were enrolled in three equal groups. Group 1 underwent scald burn injury left without treatment, the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM. Tensile strength was evaluated before and after interventions, real time PCR assessed apoptosis, and Prussian blue staining, scanning electron microscopy (SEM) and MRI were used for the tracking of labeled cells. Results: The hWJSCs exhibited mesenchymal stem cell properties. Population doubling time was 40.1 hours. SPIONs did not show any toxic effect. The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression. Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining, SEM and MRI until day 21. There was a significant difference between the Young's moduli of normal skin and the group receiving hWJSCs seeded onto an ADM. Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo. Conclusions: This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

Smart piezoelectric biomaterials for tissue engineering and regenerative medicine: a review.

Due to the presence of electric fields and piezoelectricity in various living tissues, piezoelectric materials have been incorporated into biomedical applications especially for tissue regeneration. The piezoelectric scaffolds can perfectly mimic the environment of natural tissues. The ability of scaffolds which have been made from piezoelectric materials in promoting cell proliferation and regeneration of damaged tissues has encouraged researchers in biomedical areas to work on various piezoelectric materials for fabricating tissue engineering scaffolds. In this review article, the way that cells of different tissues like cardio, bone, cartilage, bladder, nerve, skin, tendon, and ligament respond to electric fields and the mechanism of tissue regeneration with the help of piezoelectric effect will be discussed. Furthermore, all of the piezoelectric materials are not suitable for biomedical applications even if they have high piezoelectricity since other properties such as biocompatibility are vital. Seen in this light, the proper piezoelectric materials which are approved for biomedical applications are mentioned. Totally, the present review introduces the recent materials and technologies that have been used for tissue engineering besides the role of electric fields in living tissues.

Oxygen Delivery Approaches to Augment Cell Survival After Myocardial Infarction: Progress and Challenges.

Myocardial infarction (MI), triggered by blockage of a coronary artery, remains the most common cause of death worldwide. After MI, the capability of providing sufficient blood and oxygen significantly decreases in the heart. This event leads to depletion of oxygen from cardiac tissue and consequently leads to massive cardiac cell death due to hypoxemia. Over the past few decades, many studies have been carried out to discover acceptable approaches to treat MI. However, very few have addressed the crucial role of efficient oxygen delivery to the injured heart. Thus, various strategies were developed to increase the delivery of oxygen to cardiac tissue and improve its function. Here, we have given an overall discussion of the oxygen delivery mechanisms and how the current technologies are employed to treat patients suffering from MI, including a comprehensive view on three major technical approaches such as oxygen therapy, hemoglobin-based oxygen carriers (HBOCs), and oxygen-releasing biomaterials (ORBs). Although oxygen therapy and HBOCs have shown promising results in several animal and clinical studies, they still have a few drawbacks which limit their effectiveness. More recent studies have investigated the efficacy of ORBs which may play a key role in the future of oxygenation of cardiac tissue. In addition, a summary of conducted studies under each approach and the remaining challenges of these methods are discussed.

A novel substrate based on electrospun polyurethane nanofibers and electrosprayed polyvinyl alcohol microparticles for recombinant human erythropoietin delivery.

After myocardial infarction caused by a heart attack, endothelial cells need to be preserved in order to regenerate new capillaries. Moreover, sufficient mechanical support is necessary for the infarcted myocardium to pump the blood. Herein, we designed a novel substrate containing polyurethane (PU) nanofibrous layers and recombinant human erythropoietin (rhEPO)-loaded microparticles for both controlled releases of rhEPO and mechanical support of myocardium. In this system, the single-layer (SL) and double-layer (DL) PU nanofibers were electrospun, and then microparticles with different rhEPO:polyvinyl alcohol (PVA) ratios were electrosprayed on the layers. The in vitro release behavior of rhEPO from SL substrates was not satisfactory, and then the study focused on DL patches in which the release profile was in accordance with Korsmeyer-Peppas model. The release exponent of 0.89 for the DL PU/120PVA:1rhEPO represented zero-order release. The results inferred that these substrates possessed highly tailored mechanical properties; Young's modulus and ultimate tensile strength of the substrates were 74-172 kPa and 7.4-9.9 MPa, respectively. The rhEPO release from the substrates was leading to the proper adhesion of endothelial cells and more than 95% cell viability. The results indicated that the patch of elastic nanofibers and microparticles offered a potential substrate for simultaneous rhEPO delivery to endothelial cells and also mechanically supporting the infarcted myocardium.

The effect of allogenic human Wharton's jelly stem cells seeded onto acellular dermal matrix in healing of rat burn wounds.

BACKGROUND: Various methods were introduced to overcome the autograft shortage in burn wound care, including cell transplantation and tissue engineering. AIMS: To evaluate the healing effect of allogenic human Wharton's jelly stem cells (hWJSCs) seeded onto acellular dermal matrix (ADM) in rat burn injuries. PATIENTS AND METHODS: Human Wharton's jelly stem cells provided from umbilical cord tissue were characterized before transplantation, and the growth kinetic was determined. Skin samples from cosmetic surgeries were used for preparation of ADM. Forty male Sprague Dawley rats were randomly divided into 4 equal groups. Third-degree burn was induced for all animals by exposing to hot water using a 2 cm ring for 10 seconds. Group 1 was burned rats that did not receive any treatment. After burn injury, the second group received silver sulfadiazine (SSD), the third group was treated just by using ADM, and the fourth group received 2 × 106 hWJSCs seeded onto ADM. The animals were euthanized for histologic evaluation after 7, 14, and 21 days. RESULTS: Human Wharton's jelly stem cells were characterized to be spindle shape and positive for osteogenic and adipogenic induction and for mesenchymal markers but lacked hematopoietic markers. Population doubling time (PDT) was 40.1 hours with an increasing growth trend until day 6th. Macro- and microscopically, the healing was mild in ADM group and moderate in ADM + hWJSCs group after 21 days. CONCLUSION: Allogenic hWJSCs seeded onto ADM improved the healing process in burn wounds denoting to their therapeutic and anti-inflammatory effects in burn wounds that can be added to the literature.

Injectable conductive collagen/alginate/polypyrrole hydrogels as a biocompatible system for biomedical applications.

Recently, Injectable Conducting Hydrogel (ICH) systems have gained much attention for tissue engineering and regenerative medicine. These systems can promote the regeneration of tissues responding to electrical responses. In this study, a novel ICH system was introduced. To achieve this system, firstly, a soluble non-toxic polypyrrole (PPy) synthesized by grafting pyrrole on alginate (Alg) backbone (Alg-graft-PPy), and then, ICH systems were prepared by the given ratios of Alg-graft-PPy, Alg, and collagen (Col). Three different amounts of Col (0.5, 1, and 1.5 mg/ml) were added to the system including Alg-graft-PPy: Alg wt. % with the ratios of 20:80 and 30:70. FTIR spectroscopy, electrical conductivity, viscosity, syringeability, gelation time, and MTT assay were performed in order to characterize the produced hydrogels. Due to the rheological behavior of 20:80 (Alg-graft-PPy: Alg wt. %), it was recognized more suitable to inject. Also this system associated with 0.5 mg/ml Col introduced as the best sample with respect to its viscosity and injectability. This ICH system has shown high conductivity in addition to a good level of cell viability and syringeability. With respect to properties of the produced ICH system, it can be applied for bone, nerve, muscle and cardiac cells, which respond to electrical impulses.