Designing Biomimetic Conductive Gelatin-Chitosan-Carbon Black Nanocomposite Hydrogels for Tissue Engineering.

Conductive nanocomposites play a significant role in tissue engineering by providing a platform to support cell growth, tissue regeneration, and electrical stimulation. In the present study, a set of electroconductive nanocomposite hydrogels based on gelatin (G), chitosan (CH), and conductive carbon black (CB) was synthesized with the aim of developing novel biomaterials for tissue regeneration application. The incorporation of conductive carbon black (10, 15 and 20 wt.%) significantly improved electrical conductivity and enhanced mechanical properties with the increased CB content. We employed an oversimplified unidirectional freezing technique to impart anisotropic morphology with interconnected porous architecture. An investigation into whether any anisotropic morphology affects the mechanical properties of hydrogel was conducted by performing compression and cyclic compression tests in each direction parallel and perpendicular to macroporous channels. Interestingly, the nanocomposite with 10% CB produced both anisotropic morphology and mechanical properties, whereas anisotropic pore morphology diminished at higher CB concentrations (15 and 20%), imparting a denser texture. Collectively, the nanocomposite hydrogels showed great structural stability as well as good mechanical stability and reversibility. Under repeated compressive cyclic at 50% deformation, the nanocomposite hydrogels showed preconditioning, characteristic hysteresis, nonlinear elasticity, and toughness. Overall, the collective mechanical behavior resembled the mechanics of soft tissues. The electrical impedance associated with the hydrogels was studied in terms of the magnitude and phase angle in dry and wet conditions. The electrical properties of the nanocomposite hydrogels conducted in wet conditions, which is more physiologically relevant, showed a decreasing magnitude with increased CB concentrations, with a resistive-like behavior in the range 1 kHz-1 MHz and a capacitive-like behavior for frequencies <1 kHz and >1 MHz. Overall, the impedance of the nanocomposite hydrogels decreased with increased CB concentrations. Together, these nanocomposite hydrogels are compositionally, morphologically, mechanically, and electrically similar to native ECMs of many tissues. These gelatin-chitosan-carbon black nanocomposite hydrogels show great promise for use as conducting substrates for the growth of electro-responsive cells in tissue engineering.

Brain retraction injury: systematic literature review.

Cerebral retraction is frequently required in cranial surgery to access deep areas. Brain retractors have been systematically used in the past, but they have been associated with brain injury. Nonetheless, they are still used and, even recently, new systems have been advocated. The aim of this study is to provide a systematic and critical review of brain retraction injury. A systematic literature review was performed in February 2023 according to PRISMA statement. Search terms included brain retraction and injury, with their variations and pertinent associations. Studies reporting qualitative and quantitative data on brain retraction injury were included. Out of 1689 initially retrieved articles, 90 and 26 were included in the systematic review for qualitative and quantitative data, respectively. The definition of brain retraction injury varies and its reported incidence in clinical studies is 5-10%, up to 47% if cerebral edema is considered. Some studies have hypothesized threshold values of pressures to be respected in order to prevent complications, with most data deriving from animal studies. At present, there are no instruments for brain retraction that can guarantee full safety. Some form of cerebral retraction might always be necessary for specific scenarios. Further studies are needed to collect quantitative and, ideally, clinical and comparative data on pressure thresholds to develop retraction systems that can reduce injury to a minimum.

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Neurosurgery is a highly specialized field: it often involves surgical manipulation of noble structures and cerebral retraction is frequently necessary to reach deep-seated brain lesions. There are still no reliable methods preventing possible retraction complications. The objective of this study was to design work chambers well suited for transcranial endoscopic surgery while providing safe retraction of the surrounding brain tissue. The chamber is designed to be inserted close to the intracranial point of interest; once it is best placed it can be opened. This should guarantee an appreciable workspace similar to that of current neurosurgical procedures. The experimental aspect of this study involved the use of a force sensor to evaluate the pressures exerted on the brain tissue during the retraction phase. Following pterional craniotomy, pressure measurements were made during retraction with the use of a conventional metal spatula with different inclinations. Note that, although the force values necessary for retraction and exerted on the spatula by the neurosurgeon are the same, the local pressure exerted on the parenchyma at the edge of the spatula at different inclinations varied greatly. A new method of cerebral retraction using a chamber retractor (CR) has been designed to avoid any type of complication due to spatula edge overpressures and to maintain acceptable pressure values exerted on the parenchyma.

Effect of static offsets on the nonlinear dynamic mechanical properties of human brain tissue.

This study focuses on the variations in the brain tissue dynamic behaviour pointing out new insight into the material nonlinear viscoelasticity. Shear dynamic response curves are obtained in different working conditions in terms of strain sweep and superimposed static compression offsets (SCO) applied in orthogonal direction to the shear. The strain sweep mode is used to study the storage and loss moduli dependence on the amplitude of the applied strain. It is found that the material exhibits linear viscoelastic behaviour up to about 0.1% strain amplitude. Above this critical threshold, the storage modulus G' decreases rapidly with increasing dynamic strain amplitude and this effect is gradually intensified as the SCO are increased. In addition, it is observed that the loss factor (G''/G') increases by increasing the SCO applied to the specimens. The dynamic strain amplitude results of the storage modulus reveal that the elastic component of the brain tissue's stiffness (G') evaluated at low strain strongly increases with increasing static superimposed compression strain while the loss factor in the same strain range appears to be SCO independent. Finally, dynamic stiffness recovery after a large strain deformation is considered. The reduction in low amplitude dynamic modulus and subsequent recovery kinetics due to a perturbation is found to be independent of the level of the SCO. The same assessments were carried out on 5 consecutive strain sweep cycle loading. It has been noticed that at the last cycle, the dissipation peak is reduced, and the non-linearity of the curve begins earlier. This could be explained by the effects of cerebral edema on cells and their surrounding environment.

Polysaccharides on gelatin-based hydrogels differently affect chondrogenic differentiation of human mesenchymal stromal cells.

Selection of feasible hybrid-hydrogels for best chondrogenic differentiation of human mesenchymal stromal cells (hMSCs) represents an important challenge in cartilage regeneration. In this study, three-dimensional hybrid hydrogels obtained by chemical crosslinking of poly (ethylene glycol) diglycidyl ether (PEGDGE), gelatin (G) without or with chitosan (Ch) or dextran (Dx) polysaccharides were developed. The hydrogels, namely G-PEG, G-PEG-Ch and G-PEG-Dx, were prepared with an innovative, versatile and cell-friendly technique that involves two preparation steps specifically chosen to increase the degree of crosslinking and the physical-mechanical stability of the product: a first homogeneous phase reaction followed by directional freezing, freeze-drying and post-curing. Chondrogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSC) was tested on these hydrogels to ascertain whether the presence of different polysaccharides could favor the formation of the native cartilage structure. We demonstrated that the hydrogels exhibited an open pore porous morphology with high interconnectivity and the incorporation of Ch and Dx into the G-PEG common backbone determined a slightly reduced stiffness compared to that of G-PEG hydrogels. We demonstrated that G-PEG-Dx showed a significant increase of its anisotropic characteristic and G-PEG-Ch exhibited higher and faster stress relaxation behavior than the other hydrogels. These characteristics were associated to absence of chondrogenic differentiation on G-PEG-Dx scaffold and good chondrogenic differentiation on G-PEG and G-PEG-Ch. Furthermore, G-PEG-Ch induced the minor collagen proteins and the formation of collagen fibrils with a diameter like native cartilage. This study demonstrated that both anisotropic and stress relaxation characteristics of the hybrid hydrogels were important features directly influencing the chondrogenic differentiation potentiality of hBM-MSC.

Progress in the mechanical modulation of cell functions in tissue engineering.

In mammals, mechanics at multiple stages-nucleus to cell to ECM-underlie multiple physiological and pathological functions from its development to reproduction to death. Under this inspiration, substantial research has established the role of multiple aspects of mechanics in regulating fundamental cellular processes, including spreading, migration, growth, proliferation, and differentiation. However, our understanding of how these mechanical mechanisms are orchestrated or tuned at different stages to maintain or restore the healthy environment at the tissue or organ level remains largely a mystery. Over the past few decades, research in the mechanical manipulation of the surrounding environment-known as substrate or matrix or scaffold on which, or within which, cells are seeded-has been exceptionally enriched in the field of tissue engineering and regenerative medicine. To do so, traditional tissue engineering aims at recapitulating key mechanical milestones of native ECM into a substrate for guiding the cell fate and functions towards specific tissue regeneration. Despite tremendous progress, a big puzzle that remains is how the cells compute a host of mechanical cues, such as stiffness (elasticity), viscoelasticity, plasticity, non-linear elasticity, anisotropy, mechanical forces, and mechanical memory, into many biological functions in a cooperative, controlled, and safe manner. High throughput understanding of key cellular decisions as well as associated mechanosensitive downstream signaling pathway(s) for executing these decisions in response to mechanical cues, solo or combined, is essential to address this issue. While many reports have been made towards the progress and understanding of mechanical cues-particularly, substrate bulk stiffness and viscoelasticity-in regulating the cellular responses, a complete picture of mechanical cues is lacking. This review highlights a comprehensive view on the mechanical cues that are linked to modulate many cellular functions and consequent tissue functionality. For a very basic understanding, a brief discussion of the key mechanical players of ECM and the principle of mechanotransduction process is outlined. In addition, this review gathers together the most important data on the stiffness of various cells and ECM components as well as various tissues/organs and proposes an associated link from the mechanical perspective that is not yet reported. Finally, beyond addressing the challenges involved in tuning the interplaying mechanical cues in an independent manner, emerging advances in designing biomaterials for tissue engineering are also explored.

Self-repairing systems based on ionomers and epoxidized natural rubber blends.

The development of materials with the ability of intrinsic self-repairing after damage in a fashion resembling that of living tissues has important scientific and technological implications, particularly in relation to cost-effective approaches toward damage management of materials. Natural rubbers with epoxy functional groups in the macromolecular chain (ENR) and ethylene-methacrylic acid ionomers having acid groups partially neutralized with metal ions possess self-repairing behavior following high energy impacts. This research investigates the self-repairing behavior of both ENR and ionomers during ballistic puncture test on the basis of their thermal and mechanical properties. Heterogeneous blending of ionomers and ENR have also been used here as a strategy to tune the thermal and mechanical properties of the materials. Interestingly, blends of sodium ion containing ionomer exhibit complete self-repairing behavior, whereas blends of zinc ion containing ionomer show limited mending. The chemical structure studied by FTIR and thermal analysis shows that both ion content of ionomer and functionality of ENR have significant influence on the self-repairing behavior of blends. The mobility of rubbery phases along with its interaction to ionomer phase in the blends significantly changes the mending capability of materials. The healing behavior of the materials has been discussed on the basis of their thermal, mechanical, and rheological tests for each materials.