Biomaterials and tissue engineering in traumatic brain injury: novel perspectives on promoting neural regeneration.

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Cdk5 mediates rotational force-induced brain injury.

Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, and lifetime after injury. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant Cyclin-dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI. We utilized Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.

Treatment effect of exercise training on post-stroke depression in middle-aged and older adults: A meta-analysis.

OBJECTIVE: This meta-analytic study examined the effects of exercise training on depressive symptoms in mild stroke patients and the moderating effects of exercise type, therapeutic method, culture, sex, and gross domestic product (GDP) in the patient's country. METHODS: The Metafor package in R was chosen to conduct the meta-analysis, and the quality of each empirical study was evaluated according to the grading system in Cochrane. We included 36 empirical studies and 1477 patients. RESULTS: The results showed that the treatment effect of exercise training on depression in mild stroke patients was significant. The moderating effects of culture and therapeutic method were significant, but not for exercise type, sex, or GDP in the patient's country. The moderating effect of culture can be explained by the therapeutic method in different cultures. CONCLUSION: Fitness exercise is an effective method for improving depressive symptoms in mild stroke patients. Its effectiveness is moderated by the therapeutic method but is not affected by demographics, exercise type, gender, or GDP level.

Gamma Knife radiosurgery as the initial treatment for elderly patients with nonfunctioning pituitary adenomas.

PURPOSE: The aim of this study was to investigate the efficacy and safety of initial Gamma Knife radiosurgery (GKRS) for elderly patients with nonfunctioning pituitary adenomas (NFPAs). METHODS: We retrospectively reviewed 45 elderly patients underwent GKRS as the initial treatment for NFPAs at our institution between December 2007 and December 2017. Patients' radiographic and clinical data were collected. RESULTS: The median age of patients at the time of GKRS was 71 years (range 65-82 years). The median tumor volume was 2.6 cm3 (range 0.3-21.8 cm3). The median marginal dose was 13 Gy (range 6-23 Gy). The median maximum dose to the optic apparatus was 6.5 Gy (range 2.3-10.3 Gy). Thirty-five patients (77.8%) achieved tumor regression, 6 patients (13.3%) had tumor stable and 4 patients (8.9%) occurred tumor progression during a median radiological follow-up time of 51.4 months (range 11.1-158.7 months). The crude tumor control rate was 91.1%. The actuarial tumor control rates were 100%, 95.0%, 87.6%, and 87.6%, at 1, 3, 5, and 10 years after initial GKRS, respectively. New-onset hypopituitarism occurred in 6 patients. Two patients with pre-GKRS visual dysfunction developed further deterioration of visual function. No other radiation-induced complications were noted. CONCLUSION: Initial GKRS can provide a high tumor control rate as well as low risk of postradiosurgical complications for elderly patients with NFPAs. Attention should be paid to avoid radiation-related adverse effects including hypopituitarism, optic neuropathy and cranial neuropathy in elderly patients.

Mapping the Young's modulus distribution of the human tympanic membrane by microindentation.

The human tympanic membrane (TM, or eardrum) is composed primarily of layers of collagen fibers oriented in the radial and circumferential directions, as well as epidermal and mucosal layers at the lateral and medial surfaces. The mechanical properties of the TM depend on the microstructures of the collagen fibers, which vary with location, resulting in a spatial variation of Young's modulus. In this study, the Young's modulus of the human TM is measured using microindentation. A 10 µm diameter spherical nanoindenter tip is used to indent the TM at different locations in the lateral and medial surfaces. Through a viscoelastic contact analysis, the steady state out-of-plane (through thickness) Young's modulus at a constant strain rate for the TM is determined from the uniaxial relaxation modulus. The measured spatial distribution of Young's modulus is reported for the entire TM pars tensa on both lateral and medial surfaces. The Young's modulus, for the four TM quadrants, is analyzed statistically using a normal quantile-quantile (Q-Q) plot. The obtained S-shaped curve indicates a bi-modal Gaussian distribution in the Q-Q plot. The spatial distribution of the Young's modulus is modeled by a bivariate Gaussian function in the polar coordinates over the entire TM on both the lateral and medial surfaces. It is shown that the anterior-superior quadrant has the smallest value of Young's modulus. Differences are observed in the spatial distribution of the Young's modulus for both the lateral and medial surfaces. For the medial surface, Young's modulus varies mainly along the radial direction following a small-large-small trend, emanating from the umbo. For the lateral surface, the modulus at the anterior-superior quadrant shows the smallest modulus; the modulus decreases gradually along the radial directions. The quantitative results presented in this paper will help improve future simulation models of the middle ear by using spatial dependence of Young's modulus over the entire TM.

Scalable, hydrophobic and highly-stretchable poly(isocyanurate-urethane) aerogels.

Scalable, low-density and flexible aerogels offer a unique combination of excellent mechanical properties and scalable manufacturability. Herein, we report the fabrication of a family of low-density, ambient-dried and hydrophobic poly(isocyanurate-urethane) aerogels derived from a triisocyanate precursor. The bulk densities ranged from 0.28 to 0.37 g cm-3 with porosities above 70% v/v. The aerogels exhibit a highly stretchable behavior with a rapid increase in the Young's modulus with bulk density (slope of log-log plot > 6.0). In addition, the aerogels are very compressible (more than 80% compressive strain) with high shape recovery rate (more than 80% recovery in 30 s). Under tension even at high strains (e.g., more than 100% tensile strain), the aerogels at lower densities do not display a significant lateral contraction and have a Poisson's ratio of only 0.22. Under dynamic conditions, the properties (e.g., complex moduli and dynamic stress-strain curves) are highly frequency- and rate-dependent, particularly in the Hopkinson pressure bar experiment where in comparison with quasi-static compression results, the properties such as mechanical strength were three orders of magnitude stiffer. The attained outcome of this work supports a basis on the understanding of the fundamental mechanical behavior of a scalable organic aerogel with potential in engineering applications including damping, energy absorption, and substrates for flexible devices.

Characterization of the nonlinear elastic behavior of chinchilla tympanic membrane using micro-fringe projection.

The mechanical properties of an intact, full tympanic membrane (TM) inside the bulla of a fresh chinchilla were measured under quasi-static pressure from -1.0 kPa to 1.0 kPa applied on the TM lateral side. Images of the fringes projected onto the TM were acquired by a digital camera connected to a surgical microscope and analyzed using a phase-shift method to reconstruct the surface topography. The relationship between the applied pressure and the resulting volume displacement was determined and analyzed using a finite element model implementing a hyperelastic 2(nd)-order Ogden model. Through an inverse method, the best-fit model parameters for the TM were determined to allow the simulation results to agree with the experimental data. The nonlinear stress-strain relationship for the TM of a chinchilla was determined up to an equibiaxial tensile strain of 31% experienced by the TM in the experiments. The average Young's modulus of the chinchilla TM from ten bullas was determined as approximately 19 MPa.

Measurement of thickness and profile of a transparent material using fluorescent stereo microscopy.

Full-field thickness measurement for a thin transparent film is of interest for biological, medical, electronic, and packaging materials. It is a challenging task when the film is curvy, delicate and its thickness varies with location. We report herein a method to measure the thickness of a transparent (flat or curved) material and its topography using a stereo fluorescent profilometry technique. In this technique, two different types of fluorescent particles are deposited to both sides of the transparent film. Selected fluorescent excitation and emission are used to allow the observation of each one surface of the film at a time to determine the surface profile using stereo-based digital image correlation techniques. After the surface profiles for both surfaces are determined, subtraction of one surface profile from the other provides accurate thickness distribution of the film. Validation experiments were conducted using transparent films with known thickness. As an application, a measurement on a contact lens was conducted. The technique is appropriate for measurement of the full-field thickness of objects at other scales, such as soft transparent or translucent biofilms, with which thickness can hardly be measured accurately with other techniques.

Fluorescent stereo microscopy for 3D surface profilometry and deformation mapping.

Recently, mechanobiology has received increased attention. For investigation of biofilm and cellular tissue, measurements of the surface topography and deformation in real-time are a pre-requisite for understanding the growth mechanisms. In this paper, a novel three-dimensional (3D) fluorescent microscopic method for surface profilometry and deformation measurements is developed. In this technique a pair of cameras are connected to a binocular fluorescent microscope to acquire micrographs from two different viewing angles of a sample surface doped or sprayed with fluorescent microparticles. Digital image correlation technique is used to search for matching points in the pairing fluorescence micrographs. After calibration of the system, the 3D surface topography is reconstructed from the pair of planar images. When the deformed surface topography is compared with undeformed topography using fluorescent microparticles for movement tracking of individual material points, the full field deformation of the surface is determined. The technique is demonstrated on topography measurement of a biofilm, and also on surface deformation measurement of the biofilm during growth. The use of 3D imaging of the fluorescent microparticles eliminates the formation of bright parts in an image caused by specular reflections. The technique is appropriate for non-contact, full-field and real-time 3D surface profilometry and deformation measurements of materials and structures at the microscale.

Anticancer constituents and cytotoxic activity of methanol-water extract of Polygonum bistorta L.

This study was specifically designed to identify anticancer constituents in methanol-water extract of Polygonum bistorta L. and evaluate its cytotoxicity. For this purpose methanol-water (40:60 v/v) extract was subjected to conventional preparative high pressure liquid chromatography and 13 fractions were obtained. Constituents of obtained fractions were separated and identified with the help of GC-MS and LC-DAD-ESI-MS. Anticancer phenolic compounds such as gallic acid, protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanillic acid, syringic acid, catechol, 4-methyl catechol, syringol and pyrogallol and fatty acids such as linoleic acid, myristic acid and palmitic acid were separated from different fractions. Fractions were evaluated for their cytotoxic activity on a rarely studied human hepatocellular carcinoma cell line (HCCLM3). 11 fractions showed good to strong cytotoxicity in a range of 200 µg/mL-800 µg/mL, whereas 2 fractions did not show any activity even at 800 µg/mL and no anticancer constituent was detected from them. 50 percent growth inhibition (GI50) values for five most active fractions were calculated and results were in a range of 86.5 (±3) µg/mL-126.8 (±3) µg/mL. 3 out of these 5 most active fractions were found to contain phenolic content in them whereas all other fractions containing phenolic content did possess cytotoxic activity that may suggest the importance of phenolic constituents in anticancer activity. Moreover, the results also showed a definite dose dependent relationship between amount of fractions and cytotoxic activity.

Measurement of young's modulus of human tympanic membrane at high strain rates.

The mechanical behavior of human tympanic membrane (TM) has been investigated extensively under quasistatic loading conditions in the past. The results, however, are sparse for the mechanical properties (e.g., Young's modulus) of the TM at high strain rates, which are critical input for modeling the mechanical response under blast wave. The property data at high strain rates can also potentially be converted into complex modulus in frequency domain to model acoustic transmission in the human ear. In this study, we developed a new miniature split Hopkinson tension bar to investigate the mechanical behavior of human TM at high strain rates so that a force of up to half of a newton can be measured accurately under dynamic loading conditions. Young's modulus of a normal human TM is reported as 45.2-58.9 MPa in the radial direction, and 34.1-56.8 MPa in the circumferential direction at strain rates 300-2000 s(-1). The results indicate that Young's modulus has a strong dependence on strain rate at these high strain rates.