Impact of Molecular Dynamics of Polyrotaxanes on Chondrocytes in Double-Network Supramolecular Hydrogels under Physiological Thermomechanical Stimulation.

Hyaline cartilage, a soft tissue enriched with a dynamic extracellular matrix, manifests as a supramolecular system within load-bearing joints. At the same time, the challenge of cartilage repair through tissue engineering lies in replicating intricate cellular-matrix interactions. This study attempts to investigate chondrocyte responses within double-network supramolecular hybrid hydrogels tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused noncovalent host-guest polyrotaxanes, by blending α-cyclodextrins as host molecules and polyethylene glycol as guests, into a gelatin-based covalent matrix, thereby enhancing its dynamic characteristics. Subsequently, chondrocytes were seeded into these hydrogels to systematically probe the effects of two concentrations of the introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on the cellular responsiveness. Our findings unveiled an augmented level of cellular mechanosensitivity for supramolecular hydrogels compared to pure covalent-based systems. This is demonstrated by an increased mRNA expression of ion channels (TREK1, TRPV4, and PIEZO1), signaling molecules (SOX9) and matrix-remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading, which brought a stark increase in the accumulation of sulfated glycosaminoglycans and collagen. Overall, we found that matrix adaptability plays a pivotal role in modulating chondrocyte responses within double-network supramolecular hydrogels. These findings hold the potential for advancing cartilage engineering within load-bearing joints.

NIR Light-Mediated Photocuring of Adhesive Hydrogels for Noninvasive Tissue Repair via Upconversion Optogenesis.

The surgical treatments of injured soft tissues lead to further injury due to the use of sutures or the surgical routes, which need to be large enough to insert biomaterials for repair. In contrast, the use of low viscosity photopolymerizable hydrogels that can be inserted with thin needles represents a less traumatic treatment and would therefore reduce the severity of iatrogenic injury. However, the delivery of light to solidify the inserted hydrogel precursor requires a direct access to it, which is mostly invasive. To circumvent this limitation, we investigate the approach of curing the hydrogel located behind biological tissues by sending near-infrared (NIR) light through the latter, as this spectral region has the largest transmittance in biological tissues. Upconverting nanoparticles (UCNPs) are incorporated in the hydrogel precursor to convert NIR transmitted through the tissues into blue light to trigger the photopolymerization. We investigated the photopolymerization process of an adhesive hydrogel placed behind a soft tissue. Bulk polymerization was achieved with local radiation of the adhesive hydrogel through a focused light system. Thus, unlike the common methods for uniform illumination, adhesion formation was achieved with local micrometer-sized radiation of the bulky hydrogel through a gradient photopolymerization phenomenon. Nanoindentation and upright microscope analysis confirmed that the proposed approach for indirect curing of hydrogels below the tissue is a gradient photopolymerization phenomenon. Moreover, we found that the hydrogel mechanical and adhesive properties can be modulated by playing with different parameters of the system such as the NIR light power and the UCNP concentration. The proposed photopolymerization of adhesive hydrogels below the tissue opens the prospect of a minimally invasive surgical treatment of injured soft tissues.

A Platform Approach to Protein Encapsulates with Controllable Surface Chemistry.

The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient's preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (Dh) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of Dh is improved when measured at the spray dryer outlet temperature compared to room temperature (R2 = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying.

Theoretical Evaluation of the Molecular Inclusion Process between Chlordecone and Cyclodextrins: A New Method for Mitigating the Basis Set Superposition Error in the Case of an Implicit Solvation Model.

The aim of this work is to describe the molecular inclusion of chlordecone with α-, ß-, and γ-cyclodextrin in aqueous solution using quantum mechanics. The guest-host complexes of chlordecone and cyclodextrins are modeled in aqueous solution using the multiple minima hypersurface methodology with a PM6-D3H4X semiempirical Hamiltonian, and the lowest energy minima obtained are reoptimized using the M06-2X density functional and the intermolecular interactions described using quantum theory of atoms in molecules (QTAIM). The studied complexes are classified according to the degree of inclusion, namely, total occlusion, partial occlusion, and external interaction. More stable complexes are obtained when γ-CD is used as the host molecule. The interactions characterized through QTAIM analysis are all of electrostatic nature, predominantly of dispersive type. In this work, a method based on the counterpoise correction is also discussed to mitigate the basis set superposition error in density functional theory calculations when using an implicit solvation model.

Bismesitoylphosphinic Acid (BAPO-OH): A Ligand for Copper Complexes and Four-Electron Photoreductant for the Preparation of Copper Nanomaterials.

Bismesitoylphosphinic acid, (HO)PO(COMes)2 (BAPO-OH), is an efficient photoinitiator for free-radical polymerizations of olefins in aqueous phase. Described here are the structures of various copper(II) and copper(I) complexes with BAPO-OH as the ligand. The complex CuII (BAPO-O)2 (H2 O)2 is photoactive, and under irradiation with UV light in aqueous phase, it serves as a source of metallic copper in high purity and yield (>80 %). Simultaneously, the radical polymerization of acrylates can be initiated and allows the preparation of nanoparticle/polymer nanocomposites in which the metallic Cu nanoparticles are protected against oxidation. The determination of the stoichiometry of the photoreductions suggests an almost quantitative conversion from CuII into Cu0 with half an equivalent of BAPO-OH, which serves as a four-electron photoreductant.

Chitosan and chitosan-co-poly(epsilon-caprolactone) grafted multiwalled carbon nanotube transducers for vapor sensing.

Vapor sensitive transducer films consisting of chitosan grafted (CNT-CS) and chitosan-co-polycaprolactone grafted (CNT-CS-PCL) multiwalled carbon nanotubes were prepared using a spray layer-by-layer technique. The synthesized materials (CNT-CS and CNT-CS-PCL) were characterized by Fourier transform infrared spectroscopy, 13C CP/MAS solid state nuclear magnetic resonance spectroscopy and thermogravimetric analysis. Both CNT-CS and CNT-CS-PCL transducers were analyzed for the response of volatile organic compounds and toluene vapors. The ranking of the relative resistance (A(r)) for both chitosan based transducers were as follows: toluene < chloroform < ethanol < methanol. The CNT transducer (CNT-CS) was correlated selectively with an exponential law to the inverse of Flory-Huggins interaction parameters, chi12. Dosing the films on the interdigitated electrodes with methanol, ethanol, chloroform and toluene vapors increased the film resistance of CNT-CS but decreased the resistance of CNT-CS-PCL compared to that of the reported transducers.

Ileocecal knotting as a rare cause of small bowel obstruction: a case report.

Introduction: Ileocecal knot syndrome, a rare cause of small bowel obstruction where the ileum wraps around the cecum, poses a significant challenge for preoperative diagnosis. Prompt intervention is crucial due to the risk of rapid bowel deterioration and increased mortality. Case presentation: A 45-year-old female presented with central abdominal pain associated with vomiting, abdominal distension, and obstipation. On examination, she was ill-looking with hypotension, tachycardia with a feeble pulse, direct and rebound abdominal tenderness, and absent bowel sounds. Aggressive fluid resuscitation was done. Based on the clinical presentation and abdominal radiograph suggestive of intestinal obstruction, an emergency exploratory laparotomy was done, which showed an ileocecal knot and 130 cm of gangrenous ileum. Peritoneal lavage followed by resection of non-viable ileum with double barrel ileostomy was done. Discussion: Ileosigmoid, appendico-ileal, ileoileal, and ileocecal knotting are the various types of intestinal knotting, with very few cases of ileocecal knotting being reported. Intestinal knotting causes severe bowel obstruction, resulting in reduced mucosal perfusion, progressive ischemia, and peritonitis, leading to high mortality. X-ray findings of multiple air-fluid levels are non-specific, and for definitive diagnosis, laparotomy is required. Assessing bowel viability before definitive surgery is essential. Despite positive outcomes, extensive resection can lead to malabsorption and ileus, with potential risk for developing short bowel syndrome. Conclusion: Despite its rarity, the possibility of ileocecal knotting should be considered in cases of small bowel obstruction due to its potential for rapid deterioration. Prompt resuscitation followed by emergency laparotomy is necessary to prevent mortality.

Development and Performance Evaluation of Hybrid Iono-organogels for Efficient Impact Mitigation.

Dissipative materials are essential for mitigating impact in various automotive, aerospace, and sports equipment applications. This study investigates the efficiency of a novel hybrid iono-organogel in dissipating and absorbing impact energies. The gel consists of a covalently cross-linked poly(acrylic acid)-co-poly(zwitterionic (DMAPS)) in a hybrid solvent system composed of the ionic liquid [C2OHMIM][BF4] and the oligomer PEG200. The optimal solvent hybridization ratio for achieving the lowest deceleration during impact testing is 40 vol % of the ionic liquid and 60 vol % of PEG200. The gel exhibits efficient mechanical dissipative properties with a loss factor exceeding 0.5 when solicited under various dynamic conditions with this optimized ratio. Moreover, the gel demonstrates high strength and toughness, enabling it to withstand impacts without experiencing catastrophic failure. The developed gel presents stable mechanical properties over broad temperature (0-100 °C) and frequency (0.01-2000 Hz) ranges. It maintains its performance during successive impacts, thanks to its self-recovery abilities. The remarkable mechanical properties of the gel are attributed to the abundance of combined functional groups within the gel polymeric network. Indeed, reversible H-bonds, ion-dipole, and dipole-dipole interactions were observed in different studies to enhance mechanical performance. Their unique synergy effect in the developed hybrid gels held promise for better control of impact properties and durability in numerous dynamic applications.

Enhancing Robustness of Adhesive Hydrogels through PEG-NHS Incorporation.

Tissue wounds are a significant challenge for the healthcare system, affecting millions globally. Current methods like suturing and stapling have limitations as they inadequately cover the wound, fail to prevent fluid leakage, and increase the risk of infection. Effective solutions for diverse wound conditions are still lacking. Adhesive hydrogels, on the other hand, can be a potential alternative for wound care. They offer benefits such as firm sealing without leakage, easy and rapid application, and the provision of mechanical support and flexibility. However, the in vivo durability of hydrogels is often compromised by excessive swelling and unforeseen degradation, which limits their widespread use. In this study, we addressed the durability issues of the adhesive hydrogels by incorporating acrylamide polyethylene glycol N-hydroxysuccinimide (PEG-NHS) moieties (max. 2 wt %) into hydrogels based on hydroxy ethyl acrylamide (HEAam). The results showed that the addition of PEG-NHS significantly enhanced the adhesion performance, achieving up to 2-fold improvement on various soft tissues including skin, trachea, heart, lung, liver, and kidney. We further observed that the addition of PEG-NHS into the adhesive hydrogel network improved their intrinsic mechanical properties. The tensile modulus of these hydrogels increased up to 5-fold, while the swelling ratio decreased up to 2-fold in various media. These hydrogels also exhibited improved durability under the enzymatic and oxidative biodegradation induced conditions without causing any toxicity to the cells. To evaluate its potential for clinical applications, we used PEG-NHS based hydrogels to address tracheomalacia, a condition characterized by inadequate mechanical support of the airway due to weak/malacic cartilage rings. Ex vivo study confirmed that the addition of PEG-NHS to the hydrogel network prevented approximately 90% of airway collapse compared to the case without PEG-NHS. Overall, this study offers a promising approach to enhance the durability of adhesive hydrogels by the addition of PEG-NHS, thereby improving their overall performances for various biomedical applications.

Low-oxygen tension augments chondrocyte sensitivity to biomimetic thermomechanical cues in cartilage-engineered constructs.

Chondrocytes respond to various biophysical cues, including oxygen tension, transient thermal signals, and mechanical stimuli. However, understanding how these factors interact to establish a unique regulatory microenvironment for chondrocyte function remains unclear. Herein, we explore these interactions using a joint-simulating bioreactor that independently controls the culture's oxygen concentration, evolution of temperature, and mechanical loading. Our analysis revealed significant coupling between these signals, resulting in a remarkable ∼14-fold increase in collagen type II (COL2a) and aggrecan (ACAN) mRNA expression. Furthermore, dynamic thermomechanical stimulation enhanced glycosaminoglycan and COL2a protein synthesis, with the magnitude of the biosynthetic changes being oxygen dependent. Additionally, our mechanistic study highlighted the crucial role of SRY-box transcription factor 9 (SOX9) as a major regulator of chondrogenic response, specifically expressed in response to combined biophysical signals. These findings illuminate the integration of various mechanobiological cues by chondrocytes and provide valuable insights for improving the extracellular matrix content in cartilage-engineered constructs.

Unraveling cartilage degeneration through synergistic effects of hydrostatic pressure and biomimetic temperature increase.

Cartilage degeneration, typically viewed as an irreversible, vicious cycle, sees a significant reduction in two essential biophysical cues: the well-established hydrostatic pressure (HP) and the recently discovered transient temperature increase. Our study aimed to evaluate the combined influence of these cues on maintaining cartilage homeostasis. To achieve this, we developed a customized bioreactor, designed to mimic the specific hydrostatic pressure and transient thermal increase experienced during human knee physiological activities. This system enabled us to investigate the response of human 3D-cultured chondrocytes and human cartilage explants to either isolated or combined hydrostatic pressure and thermal stimuli. Our study found that chondroinduction (SOX9, aggrecan, and sulfated glycosaminoglycan) and chondroprotection (HSP70) reached maximum expression levels when hydrostatic pressure and transient thermal increase acted in tandem, underscoring the critical role of these combined cues in preserving cartilage homeostasis. These findings led us to propose a refined model of the vicious cycle of cartilage degeneration.

Wet adhesive hydrogels to correct malacic trachea (tracheomalacia) A proof of concept.

Tracheomalacia (TM) is a condition characterized by a weak tracheal cartilage and/or muscle, resulting in excessive collapse of the airway in the newborns. Current treatments including tracheal reconstruction, tracheoplasty, endo- and extra-luminal stents have limitations. To address these limitations, this work proposes a new strategy by wrapping an adhesive hydrogel patch around a malacic trachea. Through a numerical model, first it was demonstrated that a hydrogel patch with sufficient mechanical and adhesion strength can preserve the trachea's physiological shape. Accordingly, a new hydrogel providing robust adhesion on wet tracheal surfaces was synthesized employing the hydroxyethyl acrylamide (HEAam) and polyethylene glycol methacrylate (PEGDMA) as main polymer network and crosslinker, respectively. Ex vivo experiments revealed that the adhesive hydrogel patches can restrain the collapsing of malacic trachea under negative pressure. This study may open the possibility of using an adhesive hydrogel as a new approach in the difficult clinical situation of tracheomalacia.

Synthesis of γ-cyclodextrin substituted bis(acyl)phosphane oxide derivative (BAPO-γ-CyD) serving as multiple photoinitiator and crosslinking agent.

A new multi-photoactive γ-cyclodextrin substituted bis(acyl)phosphane oxide derivative (BAPO-γ-CyD) was successfully prepared via a convergent synthesis using a phospha-Michael-addition, as confirmed by 1H-, 13C-, 31P-NMR and IR spectroscopy and mass spectrometry. Kinetic studies carried out by photo-DSC and photo-rheology demonstrated its outstanding efficiency as a photoinitiator for free-radical polymerization. Remarkably, it is found that BAPO-γ-CyD also acts as a crosslinking agent to convert monofunctional methacrylate monomers into self-standing thermosetting networks with extensive swelling capability in water.

Structures and stabilities of naturally occurring cyclodextrins: a theoretical study of symmetrical conformers.

A molecular modeling study of symmetrical conformers of α-, ß-, and γ-cyclodextrins in the gas and aqueous phases was carried out using the M06-2X density functional method, with SMD employed as an implicit solvation model. Eight symmetrical conformers were found for each cyclodextrin. Values of geometrical parameters obtained from the modeling study were found to agree well with those obtained from X-ray diffraction structures. A vibrational analysis using harmonic frequencies was performed to determine thermodynamic quantities. The GIAO method was applied to determine proton and carbon-13 NMR chemical shifts, which were then compared with corresponding chemical shifts reported in the literature. Hydrogen-bonding patterns were analyzed using geometrical descriptors, and quantum chemical topology was explored by QTAIM analysis. The results of this study indicated that four of the eight conformers studied for each cyclodextrin are the most populated in aqueous solution. These results provide the foundations for future studies of host-guest complexes involving these cyclodextrins. Graphical abstract δΔGsolvation: variation of free Gibss energy of solvation.

Amphoteric amylopectin: a novel polymeric flocculant.

Novel flocculant based on amphoteric amylopectin for wastewater and industrial effluents treatment has been developed in authors' laboratory. Amphoteric flocculants have anionic and cationic moieties on the same macromolecule and is used to remove both positively and negatively charged contaminant particles in suspensions. Amylopectin based flocculants have been found to be highly efficient flocculant and hence it has been chosen as base polysaccharide. By grafting of polyacrylamide and subsequent hydrolysis, anionic amylopectin has been synthesized. Afterwards, a cationic moiety has been inserted both by chemical/microwave processing. The flocculation efficiency of the amphoteric amylopectin has been tested in kaolin and iron ore suspensions. The results indicate its high efficiency in comparison with anionic, grafted, and base amylopectin. The amphoteric amylopectin prepared via microwave irradiation showed best flocculation efficiency.