In vitro and in vivo investigation of chitosan/silk fibroin injectable interpenetrating network hydrogel with microspheres for cartilage regeneration.

Articular cartilage is an avascular and almost acellular tissue with limited self-regenerating capabilities. Although injectable hydrogels have garnered a lot of attention as a promising treatment, a biocompatible hydrogel with adequate mechanical properties is yet to be created. In this study, an interpenetrating network hydrogel comprised of chitosan and silk fibroin was created through electrostatic and hydrophobic bonds, respectively. The polymeric network of the scaffold combined an effective microenvironment for cell activity with enhanced mechanical properties to address the current issues in cartilage scaffolds. Furthermore, microspheres (MS) were utilized for a controlled release of methylprednisolone acetate (MPA), around ~75 % after 35 days. The proposed scaffolds demonstrated great mechanical stability with ~0.047 MPa compressive moduli and ~145 kPa compressive strength. Moreover, the degradation rate of the samples (~45 % after 35 days) was optimized to match neo-cartilage formation. Furthermore, the use of natural biomaterials yielded good biocompatibility with ~76 % chondrocyte viability after 7 days. According to gross observation after 12 weeks the defect site of the treated groups was filled with minimally discernible boundary. These results were confirmed by histopathology assays were the treated groups showed higher chondrocyte count and collagen type II expression.

Fabrication and characterization of an antibacterial chitosan-coated allantoin-loaded NaCMC/SA skin scaffold for wound healing applications.

The field of tissue engineering has recently emerged as one of the most promising approaches to address the limitations of conventional tissue replacements for severe injuries. This study introduces a chitosan-coated porous skin scaffold based on sodium carboxymethyl cellulose (NaCMC) and sodium alginate (SA) hydrogels, incorporating allantoin (AL) as an antibacterial agent. The NaCMC/SA hydrogel was cross-linked with epichlorohydrin (ECH) and freeze-dried to obtain a three-dimensional porous structure. The coated and non-coated scaffolds underwent comprehensive evaluation and characterization through various in-vitro analyses, including SEM imaging, swelling, degradation, and mechanical assessments. Furthermore, the scaffolds were studied regarding their allantoin (AL) release profiles, antibacterial properties, cell viability, and cell adhesion. The in-vitro analyses revealed that adding a chitosan (CS) coating and allantoin (AL) to the NaCMC/SA hydrogel significantly improved the scaffolds' antibacterial properties and cell viability. It was observed that the NaCMC:SA ratio and ECH concentration influenced the swelling capacity, biodegradation, drug release profile, and mechanical properties of the scaffolds. Samples with higher NaCMC content exhibited enhanced swelling capacity, more controlled allantoin (AL) release, and improved mechanical strength. Furthermore, the in-vivo results demonstrated that the proposed skin scaffold exhibited satisfactory biocompatibility and supported cell viability during wound healing in Wistar rats, highlighting its potential for clinical applications.

Novel size-based design of spiral microfluidic devices with elliptic configurations and trapezoidal cross-section for ultra-fast isolation of circulating tumor cells.

Investigation and analysis of circulating tumor cells (CTCs) have been valuable resources for detecting and diagnosing cancer in its early stages. Recently, enumeration and separation of CTCs via microfluidic devices have attracted significant attention due to their low cost and easy setup. In this study, novel microfluidic devices based on size-dependent cell-sorting with a trapezoidal cross-section and elliptic spiral configurations were proposed to reach label-free, ultra-fast CTCs enrichment. Firstly, the possibility and quality of separation in the devices were evaluated via a numerical simulation. Subsequently, these devices were fabricated to investigate the effects of the altering curvature and the trapezoidal cross-section on the isolation of CTCs from the peripheral blood sample at varying flow rates ranging from 0.5 mL/min to 3.5 mL/min. The experimental results indicated that the flow rate of 2.5 mL/min provided the optimal separation efficiency in the proposed devices, which was in fine agreement with the numerical analysis results. In this experiment, the purity values of CTCs between 88% and 90% were achieved, which is an indicator of the high capability of the proposed devices for the isolation and enrichment of CTCs. This strategy is hoped to overcome the limitations of classical affinity-based CTC separation approaches in the future.

Tubular TPU/SF nanofibers covered with chitosan-based hydrogels as small-diameter vascular grafts with enhanced mechanical properties.

Native grafts such as internal mammary artery and saphenous vein are the main choice for coronary artery bypass graft. However, due to the limitations associated with their availability and rapid failure caused by hyperplasia, small diameter tissue-engineered vascular grafts (TEVGs) with sufficient post-implantation patency are urgently demanded as artificial alternatives. In our previous work, we innovatively fabricated a bilayer vascular graft providing appropriate structural and biological properties using electrospinning and freeze-drying methods. It was proved that the mechanical properties of the proposed graft enhanced in comparison with using either of methods individually. Here, we adopted the same methods and incorporated an anticoagulant internal layer (inner diameter 4 mm), comprised of co-electrospun fibers of silk fibroin (SF) and heparinized thermoplastic polyurethane (TPU), and an external highly porous hydrogel fabricated by freeze-drying method. The electrospun layer exhibited strong mechanical properties including superior elastic modulus (4.92 ± 0.11 MPa), suture retention force (6.73 ± 0.83 N), elongation at break (196 ± 4%), and comparable burst pressure (1140 ± 12 mmHg) while the external hydrogel provided SMCs viability. The heparin was released in a sustain manner over 40 days, and the cytocompatibility and blood compatibility of scaffold were approved using MTT assay and platelet adhesion test. Thus, the proposed graft has a potential to be used as an artificial blood vessel scaffold for later in-vivo transplantation.

Modeling of an Ultrasound System in Targeted Drug Delivery to Abdominal Aortic Aneurysm: A Patient-Specific in Silico Study Based on Ligand-Receptor Binding.

Targeted drug delivery methods have shown a significant impact on enhancing drug delivery efficiency and reducing drug side effects. While various stimuli have been used to promote the drug delivery process, applying ultrasound (US) waves to control drug particles through the human body, noninvasively, has drawn the scientist's attention. However, microcarriers delivery reaches the aneurysmal artery by US waves that exert volumetric forces on blood, and drug carriers, which can therefore affect blood flow patterns and movement pathways of drug carriers, have not yet been studied. In this study, we developed a 3-D patient-specific model of abdominal aortic aneurysm (AAA) to evaluate the effect of US waves in enhancing the drug-containing microbubbles (MBs) adhered on the AAA lumen through ligand-receptor binding. Thus, a focused US (FUS) transducer with a resonance frequency of ~1.1 MHz was added to the geometry. Then, the surface density of MBs (SDM) adhered on the AAA lumen was calculated at peak acoustic pressure of ~1.1, ~2.2, and ~4.3 MPa. Results indicated that increasing the US pressure had a significant impact on improving the MBs adhered to the intended wall, whereby US waves with the maximum pressure of ~4.3 MPa could enhance ~1- [Formula: see text] MBs adhesion ~98% relative to not using the waves. While US waves have the advantage of more SDM adhered to the whole artery wall, they adversely affect the SDM adhered on the critical wall of the abdominal aorta. Furthermore, when the US strength goes up, a reduction occurs in the SDM adhered. This reduction is higher for smaller MBs, which is the mentioned MBs' size and US strength reduced SDM adhesion by about ~50% relative to systemic injection. Therefore, it can be concluded that drug delivery using the US field increases the SDM adhered to the whole AAA wall and decreases the SDM adhered to the critical wall of AAA.

The Shapley value for a fair division of group discounts for coordinating cooling loads.

We consider a demand response program in which a block of apartments receive a discount from their electricity supplier if they ensure that their aggregate load from air conditioning does not exceed a predetermined threshold. The goal of the participants is to obtain the discount, while ensuring that their individual temperature preferences are also satisfied. As such, the apartments need to collectively optimise their use of air conditioning so as to satisfy these constraints and minimise their costs. Given an optimal cooling profile that secures the discount, the problem that the apartments face then is to divide the total discounted cost in a fair way. To achieve this, we take a coalitional game approach and propose the use of the Shapley value from cooperative game theory, which is the normative payoff division mechanism that offers a unique set of desirable fairness properties. However, applying the Shapley value in this setting presents a novel computational challenge. This is because its calculation requires, as input, the cost of every subset of apartments, which means solving an exponential number of collective optimisations, each of which is a computationally intensive problem. To address this, we propose solving the optimisation problem of each subset suboptimally, to allow for acceptable solutions that require less computation. We show that, due to the linearity property of the Shapley value, if suboptimal costs are used rather than optimal ones, the division of the discount will be fair in the following sense: each apartment is fairly "rewarded" for its contribution to the optimal cost and, at the same time, is fairly "penalised" for its contribution to the discrepancy between the suboptimal and the optimal costs. Importantly, this is achieved without requiring the optimal solutions.