A comprehensive bench-to-bed look into the application of gamma-sterilized 3D-printed polycaprolactone/hydroxyapatite implants for craniomaxillofacial defects, an in vitro, in vivo, and clinical study.

This study investigates the safety and efficacy of 3D-printed polycaprolactone/hydroxyapatite (PCL/HA) scaffolds for patient-specific cranioplasty surgeries, employing liquid deposition modeling (LDM) technology. This research is pioneering as it explores the impact of gamma radiation on PCL/HA scaffolds and utilizes printing ink with the highest content of HA known in the composite. The mechanical, morphological, and macromolecular stability of the gamma-sterilized scaffolds were verified before implantation. Subsequent research involving animal subjects was conducted to explore the effects of sterilized implants. Eventually, three clinical cases were selected for the implantation studies as part of a phase 1 non-randomized open-label clinical trial. It was shown that a 25 kGy gamma-ray dose for sterilizing the printed implants did not alter the required geometrical precision of the printed implants. The implants exhibited well-distributed HA and strength comparable to cancellous bone. Gamma radiation reduced hydrophobicity and water uptake capacity without inducing pyrogenic or inflammatory responses. Personalized PCL/HA substitutes successfully treated various craniomaxillofacial defects, including trauma-induced facial asymmetry and congenital deformities. HA nanoparticles in the ink stimulated significant osteoconductive responses within three months of implantation. Moreover, the results revealed that while larger implants may exhibit a slower bone formation response in comparison to smaller implants, they generally had an acceptable rate and volume of bone formation. This clinical trial suggests the application of a sterilized PCL/HA composite for craniomaxillofacial surgery is safe and could be considered as a substitute for autologous bone.

Platelet rich fibrin and simvastatin-loaded pectin-based 3D printed-electrospun bilayer scaffold for skin tissue regeneration.

Designing multifunctional wound dressings is a prerequisite to prevent infection and stimulate healing. In this study, a bilayer scaffold (BS) with a top layer (TL) comprising 3D printed pectin/polyacrylic acid/platelet rich fibrin hydrogel (Pec/PAA/PRF) and a bottom nanofibrous layer (NL) containing Pec/PAA/simvastatin (SIM) was produced. The biodegradable and biocompatible polymers Pec and PAA were cross-linked to form hydrogels via Ca2+ activation through galacturonate linkage and chelation, respectively. PRF as an autologous growth factor (GF) source and SIM together augmented angiogenesis and neovascularization. Because of 3D printing, the BS possessed a uniform distribution of PRF in TL and an average fiber diameter of 96.71 ± 18.14 nm was obtained in NL. The Young's modulus of BS was recorded as 6.02 ± 0.31 MPa and its elongation at break was measured as 30.16 ± 2.70 %. The wound dressing gradually released growth factors over 7 days of investigation. Furthermore, the BS significantly outperformed other groups in increasing cell viability and in vivo wound closure rate (95.80 ± 3.47 % after 14 days). Wounds covered with BS healed faster with more collagen deposition and re-epithelialization. The results demonstrate that the BS can be a potential remedy for skin tissue regeneration.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Antimicrobial activity and wound healing effect of a novel natural ointment: an in vitro and in vivo study.

Infection and pathological disorders, such as cellular disorders, ischaemia, neuropathy and angiogenesis, are considered the most critical factors which cause a delay in the wound healing process in patients with diabetes. This study aimed to investigate the effect of an ointment based on ostrich oil containing honey, beeswax, and ethanolic extracts of Nigella sativa, propolis and Cassia angustifolia on the wound healing process of diabetic rats. Gas chromatography/mass spectrometry analysis showed caffeic acid and pinostrobin chalcone molecules present in propolis, giving antibacterial and antifungal properties to the compound. The antibacterial assessment showed the ointment had remarkable antibacterial activity against Staphylococcus aureus (8.6±0.28mm), Escherichia coli (9.4±0.31mm), Acinetobacter baumannii (7.2±0.23mm) and Pseudomonas aeruginosa (13.9±0.42mm). In vivo results showed the ointment significantly accelerated wound healing and increased collagen deposition compared with the control (p<0.05). Histopathology evaluation also showed hair follicles, sebaceous glands and vessels in the group that used the ointment. These results proved successful and diabetic wound healing was rapid. Therefore, it could be concluded that the fabricated ointment could be a suitable candidate for wound healing.

Antioxidant, Antimicrobial and Antiviral Properties of Herbal Materials.

Recently, increasing public concern about hygiene has been driving many studies to investigate antimicrobial and antiviral agents. However, the use of any antimicrobial agents must be limited due to their possible toxic or harmful effects. In recent years, due to previous antibiotics' lesser side effects, the use of herbal materials instead of synthetic or chemical drugs is increasing. Herbal materials are found in medicines. Herbs can be used in the form of plant extracts or as their active components. Furthermore, most of the world's populations used herbal materials due to their strong antimicrobial properties and primary healthcare benefits. For example, herbs are an excellent material to replace nanosilver as an antibiotic and antiviral agent. The use of nanosilver involves an ROS-mediated mechanism that might lead to oxidative stress-related cancer, cytotoxicity, and heart diseases. Oxidative stress further leads to increased ROS production and also delays the cellular processes involved in wound healing. Therefore, existing antibiotic drugs can be replaced with biomaterials such as herbal medicine with high antimicrobial, antiviral, and antioxidant activity. This review paper highlights the antibacterial, antiviral, and radical scavenger (antioxidant) properties of herbal materials. Antimicrobial activity, radical scavenger ability, the potential for antimicrobial, antiviral, and anticancer agents, and efficacy in eliminating bacteria and viruses and scavenging free radicals in herbal materials are discussed in this review. The presented herbal antimicrobial agents in this review include clove, portulaca, tribulus, eryngium, cinnamon, turmeric, ginger, thyme, pennyroyal, mint, fennel, chamomile, burdock, eucalyptus, primrose, lemon balm, mallow, and garlic, which are all summarized.

Polyurethane nanocomposite impregnated with chitosan-modified graphene oxide as a potential antibacterial wound dressing.

In this study, a polyurethane nanocomposite film (PU/CS-GO) was synthesized by incorporating chitosan-modified GO nanosheets (CS-GO) into PU matrices. The successful synthesis of unmodified GO and CS-GO nanosheets was confirmed by FTIR, XRD, Raman, SEM, EDS, and TGA analyses. In comparison with polyurethane nanocomposite containing unmodified graphene oxide (PU/GO), the effect of the modification of GO with chitosan on different properties such as morphological, thermal, thermo-mechanical, wettability, antibacterial, and biocompatibility properties was evaluated by various analyses including XRD, FE-SEM, TGA, DMTA, contact angle, antibacterial studies, and MTT assay. FE-SEM images exhibited better dispersion of CS-GO nanosheets within polyurethane matrices compared to GO nanosheets. According to DMTA results, PU/CS-GO showed a higher glass transition temperature (Tg) and storage modulus values than PU/GO sample. Based on antibacterial and MTT assays, in comparison with PU/GO, the PU/CS-GO nanocomposite demonstrated better biocompatibility and also antibacterial activity against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. Based on results, the PU/CS-GO nanocomposite can be suggested as a promising material for antibacterial wound dressing.

Electrospun Nano-Fibers for Biomedical and Tissue Engineering Applications: A Comprehensive Review.

Pharmaceutical nano-fibers have attracted widespread attention from researchers for reasons such as adaptability of the electro-spinning process and ease of production. As a flexible method for fabricating nano-fibers, electro-spinning is extensively used. An electro-spinning unit is composed of a pump or syringe, a high voltage current supplier, a metal plate collector and a spinneret. Optimization of the attained nano-fibers is undertaken through manipulation of the variables of the process and formulation, including concentration, viscosity, molecular mass, and physical phenomenon, as well as the environmental parameters including temperature and humidity. The nano-fibers achieved by electro-spinning can be utilized for drug loading. The mixing of two or more medicines can be performed via electro-spinning. Facilitation or inhibition of the burst release of a drug can be achieved by the use of the electro-spinning approach. This potential is anticipated to facilitate progression in applications of drug release modification and tissue engineering (TE). The present review aims to focus on electro-spinning, optimization parameters, pharmacological applications, biological characteristics, and in vivo analyses of the electro-spun nano-fibers. Furthermore, current developments and upcoming investigation directions are outlined for the advancement of electro-spun nano-fibers for TE. Moreover, the possible applications, complications and future developments of these nano-fibers are summarized in detail.

A Review of Controlled Drug Delivery Systems Based on Cells and Cell Membranes.

Novel drug delivery systems have ameliorated drugs' pharmacokinetics and declined undesired ramifications while led to a better patient compliance by extending the time of release. In fact, although there has been a multitude of encouraging achievements in controlled drug release, the application of micro- and nano-carriers is confronted with some challenges such as rapid clearance and inefficient targeting. In addition, since cell systems can be an appropriate alternative to micro- and nano-particles, they have been used as biological carriers. In general, features such as stable release into blood, slow clearance, efficient targeting, and high biocompatibility are the main properties of cells applied as drug carriers. Furthermore, some cells such as erythrocytes, leukocytes, stem cells, and platelets have been used as release systems. Hence, most common cells that were used as aforementioned release systems are going to be presented in this review article.

Characterization of Silk/Poly 3-Hydroxybutyrate-chitosan-multi-walled Carbon Nanotube Micro-nano Scaffold: A New Hybrid Scaffold for Tissue Engineering Applications.

BACKGROUND: Long-term healing tissue engineering scaffolds must hold its full mechanical strength at least for 12 weeks. Nano-micro scaffolds consist of electrospinning nanofibers and textile microfibers to support cell behavior and mechanical strength, respectively. METHODS: The new nano-micro hybrid scaffold was fabricated by electrospinning poly 3-hydroxybutyrate-chitosan-multi-walled carbon nanotube (MWNT functionalized by COOH) solution on knitted silk in a random manner with different amounts of MWNT. The physical, mechanical, and biodegradation properties were assessed through scanning electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, water contact angle test, tensile strength test, and weight loss test. The scaffold without MWNT was chosen as control sample. RESULTS: An increase in the amount of MWNT up to 1 wt% leads to better fiber diameter distribution, more hydrophilicity, biodegradation rate, and higher tensile strength in comparison with other samples. The porosity percentage of all scaffolds is more than 80%. According to FTIR spectra, the nanofibrous coat on knitted silk did not have any effect on silk fibroin crystallinity structures, and according to tensile strength test, the coat had a significant effect on tensile strength in comparison with pure knitted silk (P ≤ 0.05). The average fiber diameter decreased due to an increase in electrical conductivity of the solution and fiber stretch in electrical field due to MWNTs. The scaffold containing 1 wt% MWNT was more hydrophilic due to the presence of many COOH groups of functionalized MWNT, thus an increase in the hydrolysis and degradation rate of this sample. CONCLUSIONS: High intrinsic tensile strength of MWNTs and improvement of nano-micro interface connection lead to an increase in tensile strength in scaffolds containing MWNT.