Antimicrobial peptide immobilization on catechol-functionalized PCL/alginate wet-spun fibers to combat surgical site infection.

Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength via hydrogen bonds. Having an average diameter of 220 µm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of Proteus spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity.

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Design of experiment approach to identify the dominant geometrical feature of left coronary artery influencing atherosclerosis.

Background and Objective. Coronary artery geometry heavily influences local hemodynamics, potentially leading to atherosclerosis. Consequently, the unique geometrical configuration of an individual by birth can be associated with future risk of atherosclerosis. Although current researches focus on exploring the relationship between local hemodynamics and coronary artery geometry, this study aims to identify the order of influence of the geometrical features through systematic experiments, which can reveal the dominant geometrical feature for future risk assessment.Methods. According to Taguchi's method of design of experiment (DoE), the left main stem (LMS) length (lLMS), curvature (kLMS), diameter (dLMS) and the bifurcation angle between left anterior descending (LAD) and left circumflex (LCx) artery (αLAD-LCx) of two reconstructed patient-specific left coronary arteries (LCA) were varied in three levels to create L9 orthogonal array. Computational fluid dynamic (CFD) simulations with physiological boundary conditions were performed on the resulting eighteen LCA models. Average helicity intensity (h2) and relative atheroprone area (RAA) of near-wall hemodynamic descriptors were analyzed.Results. The proximal LAD (LADproximal) was identified to be the most atheroprone region of the left coronary artery due to higherh2,large RAA of time averaged wall shear stress (TAWSS < 0.4 Pa), oscillatory shear index (OSI ∼ 0.5) and relative residence time (RRT > 4.17 Pa-1). In both patient-specific cases, based onh2and TAWSS,dlmsis the dominant geometric parameter while based on OSI and RRT,αLAD-LCxis the dominant one influencing hemodynamic condition in proximal LAD (p< 0.05). Based on RRT, the rank of the geometrical factors is:αLAD-LCx>dLMS>lLMS>kLMS, indicating thatαLAD-LCxis the most dominant geometrical factor affecting hemodynamics at proximal LAD which may influence atherosclerosis.Conclusion. The proposed identification of the rank of geometrical features of LCA and the dominant feature may assist clinicians in predicting the possibility of atherosclerosis, of an individual, long before it will occur. This study can further be translated to be used to rank the influence of several arterial geometrical features at different arterial locations to explore detailed relationships between the arterial geometrical features and local hemodynamics.

Chitosan-Stabilized CuO Nanostructure-Functionalized UV-Crosslinked PVA/Chitosan Electrospun Membrane as Enhanced Wound Dressing.

Electrospun nanofibrous membranes are of great interest for tissue engineering, active material delivery, and wound dressing. These nanofibers possess unique three-dimensional (3D) interconnected porous structures that result in a higher surface-area-to-volume ratio and porosity. This study was carried out to prepare nanofibrous membranes by electrospinning a blend of PVA/chitosan polymeric solution functionalized with different ratios of copper oxide. Chitosan-stabilized CuO nanoparticles (CH-CuO NPs) were biosynthesized successfully utilizing chitosan as the capping and reducing agent. XRD analysis confirmed the monoclinic structure of CH-CuO NPs. In addition, the electrospun nanofibrous membranes were UV-crosslinked for a definite time. The membranes containing CH-CuO NPs were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectrophotometry, and dynamic light scattering (DLS). SEM results showed the nanosize of the fiber diameter in the range of 147-207 nm. The FTIR spectroscopy results indicated the successful incorporation of CH-CuO NPs into the PVA/chitosan nanofibrous membranes. DSC analysis proved the enhanced thermal stability of the nanofibrous membranes due to UV-crosslinking. Swelling and degradation tests were carried out to ensure membrane stability. Greater antimicrobial activity was observed in the nanoparticle-loaded membrane. An in vitro release study of Cu2+ ions from the membrane was carried out for 24 h. The cytotoxicity of CH-CuO NP-incorporated membranes was investigated to estimate the safe dose of nanoparticles. An in vivo test using the CH-CuO NP-loaded PVA/chitosan membrane was conducted on a mice model, in which wound healing occurred in approximately 12 days. These results confirmed that the biocompatible, nontoxic nanofibrous membranes are ideal for wound-dressing applications.

Self-assembled sodium alginate polymannuronate nanoparticles for synergistic treatment of ophthalmic infection and inflammation: Preparation optimization and in vitro/vivo evaluation.

Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery.

Advances in Transdermal Delivery of Antimicrobial Peptides for Wound Management: Biomaterial-Based Approaches and Future Perspectives.

Antimicrobial peptides (AMPs), distinguished by their cationic and amphiphilic nature, represent a critical frontier in the battle against antimicrobial resistance due to their potent antimicrobial activity and a broad spectrum of action. However, the clinical translation of AMPs faces hurdles, including their susceptibility to degradation, limited bioavailability, and the need for targeted delivery. Transdermal delivery has immense potential for optimizing AMP administration for wound management. Leveraging the skin's accessibility and barrier properties, transdermal delivery offers a noninvasive approach that can circumvent systemic side effects and ensure sustained release. Biomaterial-based delivery systems, encompassing nanofibers, hydrogels, nanoparticles, and liposomes, have emerged as key players in enhancing the efficacy of transdermal AMP delivery. These biomaterial carriers not only shield AMPs from enzymatic degradation but also provide controlled release mechanisms, thereby elevating stability and bioavailability. The synergistic interaction between the transdermal approach and biomaterial-facilitated formulations presents a promising strategy to overcome the multifaceted challenges associated with AMP delivery. Integrating advanced technologies and personalized medicine, this convergence allows the reimagining of wound care. This review amalgamates insights to propose a pathway where AMPs, transdermal delivery, and biomaterial innovation harmonize for effective wound management.

Xanthan and gum acacia modified olive oil based nanoemulsion as a controlled delivery vehicle for topical formulations.

In this study, olive oil nanoemulsion modified with xanthan gum and gum acacia was explored as a potential controlled topical delivery vehicle. Oil-in-water nanoemulsion formulated with optimized composition of olive oil, tween 80, and water was used as the drug carrier and further modified with gum. Effect of gum on nanoemulsion different physiochemical characteristics, stability, rheology, drug release and encapsulation efficiency were investigated. Results showed that developed nanoemulsion behaved as low viscosity Newtonian fluid and released 100 % drug within 6 h. Modification with xanthan and gum acacia had significantly improved formulation viscosity, drug encapsulation efficiency (>85 %) and controlled drug release up to 40 % with release pattern following Korsmeyer-Peppas model. Additionally, xanthan gum modified formulation exhibited shear thinning rheology by forming an extended network in the continuous phase, whereas gum acacia modified formulation behaved as Newtonian fluid at high shear rate (>200 s-1). Furthermore, xanthan gum modified formulations had improved zeta potential, stability, monodispersity, and hemocompatibility and showed high antibacterial activity against S. aureus than gum acacia modified formulations. These results indicate the higher potential of xanthan gum modified formulation as a topical delivery vehicle. Moreover, skin irritation test demonstrated the safety of developed formulations for topical application.

Segmenting 3D geometry of left coronary artery from coronary CT angiography using deep learning for hemodynamic evaluation.

While coronary CT angiography (CCTA) is crucial for detecting several coronary artery diseases, it fails to provide essential hemodynamic parameters for early detection and treatment. These parameters can be easily obtained by performing computational fluid dynamic (CFD) analysis on the 3D artery geometry generated by CCTA image segmentation. As the coronary artery is small in size, manually segmenting the left coronary artery from CCTA scans is a laborious, time-intensive, error-prone, and complicated task which also requires a high level of expertise. Academics recently proposed various automated segmentation techniques for combatting these issues. To further aid in this process, we present CoronarySegNet, a deep learning-based framework, for autonomous and accurate segmentation as well as generation of 3D geometry of the left coronary artery. The design is based on the original U-net topology and includes channel-aware attention blocks as well as deep residual blocks with spatial dropout that contribute to feature map independence by eliminating 2D feature maps rather than individual components. We trained, tested, and statistically evaluated our model using CCTA images acquired from various medical centers across Bangladesh and the Rotterdam Coronary Artery Algorithm Evaluation challenge dataset to improve generality. In empirical assessment, CoronarySegNet outperforms several other cutting-edge segmentation algorithms, attaining dice similarity coefficient of 0.78 on an average while being highly significant (p < 0.05). Additionally, both the 3D geometries generated by machine learning and semi-automatic method were statistically similar. Moreover, hemodynamic evaluation performed on these 3D geometries showed comparable results.

The effects of plaque morphological characteristics on the post-stenotic flow in left main coronary artery bifurcation.

Local post-stenotic hemodynamics has critical influence in the atherosclerotic plaque progression occurring in susceptible arterial sites, in particular the left main coronary artery (LMCA) bifurcation. Understanding the effects of plaque morphological characteristics: stenosis severity (SS), eccentricity index (EI) and lesion length (LL) on the post-stenotic flow behavior can significantly improve treatment planning. In order to investigate these effects, we have employed computational fluid dynamics (CFD) simulations in twenty computer-generated and five patient-specific LMCA models and the hemodynamic parameters: velocity, pressure (P), wall pressure gradient (WPG), wall shear stress (WSS), time averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT) and helicity intensity (h2) were analyzed. Our results revealed that the effect of stenosis eccentricity varied significantly for different values of stenosis severity and lesion length. Regions with low WSS, low TAWSS and high RRT were more prominent in models having higher stenosis severity. For smaller lesion length, at low and moderate stenosis severity, surface area with low TAWSS and high RRT decreased with increasing eccentricity index, whereas for high stenosis severity models, low TAWSS region and average RRT values increased with eccentricity. However, for models with longer lesion length, regions with high OSI and RRT overall increased gradually with eccentricity. The helicity intensity (h2) of all models remained very low except at the most eccentric model with longer lesion length. The presence of very high helical flow in this model suggests the possibility of atheroprotective flow. It can be concluded that all plaque morphological characteristics covered under this investigation play an important role in plaque progression.

Preparation of different polymorphs of cellulose from different acid hydrolysis medium.

In this study, medical cotton was subjected to acid hydrolysis in sulfuric, hydrochloric and phosphoric acid medium to prepare cellulose nanocrystals (CNC) with different morphologies and polymorphism. Morphology of the prepared CNC samples revealed fiber shaped morphology for sulfuric and hydrochloric acid hydrolyzed samples, whereas, spherical shaped for phosphoric acid hydrolyzed samples. The size of the spherical shaped CNC decreased with the increase of hydrolysis time, from 853 nm for 12 h to 187 nm for 48 h. X-ray Diffraction analysis showed that hydrochloric acid hydrolyzed CNC is cellulose I (CI), phosphoric acid hydrolyzed CNC is cellulose II (CII) and sulfuric acid hydrolyzed CNC contain both CI and CII. The crystallinity of sulfuric and hydrochloric acid hydrolysis samples was 91%, whereas, the crystallinity of phosphoric acid hydrolysis samples was between 43 and 60% depending on hydrolysis time. Thermal properties were also affected by the hydrolysis medium. Thus cellulose nanocrystals were prepared with different morphologies and physical characteristics through a facile method.

Fabrication of polycaprolactone-silanated ß-tricalcium phosphate-heparan sulfate scaffolds for spinal fusion applications.

BACKGROUND CONTEXT: Interbody spinal fusion relies on the use of external fixation and the placement of a fusion cage filled with graft materials (scaffolds) without regard for their mechanical performance. Stability at the fusion site is instead reliant on fixation hardware combined with a selected cage. Ideally, scaffolds placed into the cage should both support the formation of new bone and contribute to the mechanical stability at the fusion site. PURPOSE: We recently developed a scaffold consisting of silane-modified PCL-TCP (PCL-siTCP) with mechanical properties that can withstand the higher loads generated in the spine. To ensure the scaffold more closely mimicked the bone matrix, we incorporated collagen (Col) and a heparan sulfate glycosaminoglycan sugar (HS3) with increased affinity for heparin-binding proteins such as bone morphogenetic protein-2 (BMP-2). The osteostimulatory characteristic of this novel device delivering exogenous BMP2 was assessed in vitro and in vivo as a prelude to future spinal fusion studies with this device. STUDY DESIGN/SETTING: A combination of cell-free assays (BMP2 release), progenitor cell-based assays (BMP2 bioactivity, cell proliferation and differentiation), and rodent ectopic bone formation assays was used to assess the osteostimulatory characteristics of the PCL-siTCP-based scaffolds. MATERIALS AND METHODS: Freshly prepared rat mesenchymal stem cells were used to determine reparative cell proliferation and differentiation on the PCL-siTCP-based scaffolds over a 28-day period in vitro. The bioactivity of BMP2 released from the scaffolds was assessed on progenitor cells over a 28-day period using ALP activity assays and release kinetics as determined by enzyme-linked immunosorbent assay. For ectopic bone formation, intramuscular placement of scaffolds into Sprague Dawley rats (female, 4 weeks old, 120-150 g) was achieved in five animals, each receiving four treatments randomized for location along the limb. The four groups tested were (1) PCL-siTCP/Col (5-mm diameter×1-mm thickness), PCL-siTCP/Col/BMP2 (5 µg), (3) PCL-siTCP/Col/HS3 (25 µg), and (4) PCL-siTCP/Col/HS3/BMP2 (25 and 5 µg, respectively). Bone formation was evaluated at 8 weeks post implantation by microcomputed tomography (µCT) and histology. RESULTS: Progenitor cell-based assays (proliferation, mRNA transcripts, and ALP activity) confirmed that BMP2 released from PCL-siTCP/Col/HS3 scaffolds increased ALP expression and mRNA levels of the osteogenic biomarkers Runx2, Col1a2, ALP, and bone gla protein-osteocalcin compared with devices without HS3. When the PCL-siTCP/Col/HS3/BMP2 scaffolds were implanted into rat hamstring muscle, increased bone formation (as determined by two-dimensional and three-dimensional µCTs and histologic analyses) was observed compared with scaffolds lacking BMP2. More consistent increases in the amount of ectopic bone were observed for the PCL-siTCP/Col/HS3/BMP2 implants compared with PCL-siTCP/Col/BMP2. Also, increased mineralizing tissue within the pores of the scaffold was seen with modified-tetrachrome histology, a result confirmed by µCT, and a modest but detectable increase in both the number and the thickness of ectopic bone structures were observed with the PCL-siTCP/Col/HS3/BMP2 implants. CONCLUSIONS: The combination of PCL-siTCP/Col/HS3/BMP2 thus represents a promising avenue for further development as a bone graft alternative for spinal fusion surgery.

Wet-spinnability and crosslinked fibre properties of two collagen polypeptides with varied molecular weight.

The formation of naturally derived materials with wet stable fibrous architectures is paramount in order to mimic the features of tissues at the molecular and microscopic scale. Here, we investigated the formation of wet-spun fibres based on collagen-derived polypeptides with comparable chemical composition and varied molecular weight. Gelatin and hydrolysed fish collagen (HFC) were selected as widely available linear amino-acidic chains of high and low molecular weight, respectively, and functionalised in the wet-spun fibre state in order to preserve the material geometry in physiological conditions. Wet-spun fibre diameter and morphology were dramatically affected depending on the polypeptide molecular weight, wet-spinning solvent (i.e. 2,2,2-trifluoroethanol and dimethyl sulfoxide) and coagulating medium (i.e. acetone and ethanol), resulting in either bulky or porous internal geometry. Dry-state tensile moduli were significantly enhanced in gelatin and HFC samples following covalent crosslinking with activated 1,3-phenylenediacetic acid (Ph) (E: 726±43-844±85MPa), compared to samples crosslinked via intramolecular carbodiimide-mediated condensation reaction (E: 588±38MPa). Resulting fibres displayed a dry diameter in the range of 238±18-355±28µm and proved to be mechanically stable (E: 230kPa) following equilibration with PBS, whilst a nearly complete degradation was observed after 5-day incubation in physiological conditions.

Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering.