Spherical Tissues Research Articles

Geometrical incompatibility regulated pattern selection and morphological evolution in growing spherical soft tissues

Surface morphological patterns are widely observed in natural systems, which are closely correlated to vital biological functions and inspire surface morphology designs in soft matter systems. Geometrical incompatibility widely exists in biological tissues across different length scales and plays an important role in growth-induced pattern selection and morphological evolution of soft tissues. However, the underlying physical mechanism of growth-induced pattern formation and post-buckling evolution in geometrically incompatible spherical soft tissues remain elusive. Here, the effect of geometrical incompatibility on the growth-induced pattern selection and post-buckling evolution are investigated through swelling experiment, theoretical analysis and numerical simulation. The results show that not only the instability pattern but also the instability threshold can be regulated by manipulating geometric incompatibility. Notably, when the geometrical incompatibility parameter exceeds a critical value, spontaneous instability is observed before growth. With continuous growth, the core–shell soft sphere buckles into a periodic buckyball pattern and evolves toward a bean-shaped pattern, and then undergoes a wrinkle-to-fold transition into a labyrinth topography. Our results demonstrate, both experimentally and theoretically, that geometrical incompatibility can guide the growth-induced pattern formation and morphological evolution effectively. This study not only enhances our understanding of the growth-induced pattern selection and morphological evolution in spherical soft tissues, but also provides an inspiring insight for the fabrication of morphological patterns on curved surfaces.

Emergent chirality in active solid rotation of pancreas spheres

Collective cell dynamics play a crucial role in many developmental and physiological contexts. While two-dimensional (2D) cell migration has been widely studied, how three-dimensional (3D) geometry and topology interplay with collective cell behavior to determine dynamics and functions remains an open question. In this work, we elucidate the biophysical mechanism underlying rotation in spherical tissues, a phenomenon widely reported both and . Using murine pancreas-derived organoids as a model system, we find that epithelial spheres exhibit persistent rotation, rotational axis drift, and rotation arrest. Using a 3D vertex model, we demonstrate how the combined action of traction force and polarity alignment can account for these distinct rotational dynamics near a solid to flow transition. Furthermore, our analysis shows that the spherical tissue rotates as an active solid occasionally switching to a flowing state and exhibits spontaneous chiral symmetry breaking. Using a continuum model, we demonstrate how the topological defects in the polarity field underlie this symmetry breaking process, which is revealed by asymmetries in the cell elongation pattern. For cell elongation to reveal the chiral asymmetry, shear flow is required in addition to the solid body rotation. Altogether, our work reveals a robust chiral symmetry breaking mechanism with potential implications for left-right symmetry breaking processes in morphogenetic events. Published by the American Physical Society 2024

A numerical approach to the stability analysis of growing cylindrical tubes and spherical tissues

In this paper, the effect of growth on the stability of elastic materials is examined through a numerical approach. Growth and resorption are considered to have two main effects from the stability standpoint. Corresponding to the change in mass, the geometry of a system changes, and the critical length of the system can be modified. In addition, the growth of the material may be affected by the stress, yet it may also impose residual stresses. As a result, the material is either stabilized or destabilized by these stresses. As a general framework for the description of elastic properties, the theory of finite elasticity is employed to investigate the growth of elastic materials. Growth is taken into account through matrix multiplication of the deformation gradient. The formalism of incremental deformation is adopted to consider growth effects. Using this formalism, the stability of growing neo-Hookean incompressible cylindrical and spherical shells under external pressure is considered. Firstly, the incremental equilibrium equations and the corresponding boundary conditions for the incompressible growing shells are summarized and afterward employed in order to analyze the behavior of spherical and cylindrical shells subjected to external pressure. The generalized differential quadrature method (GDQ) is utilized to solve the eigenvalue problem that results from a linear bifurcation analysis. It is shown that this numerical method can be efficiently utilized to solve the considered problem. The results are in full agreement with the previously obtained results. In the presence of external radial pressure, an elastic shell will buckle circumferentially to a noncircular cross-section. A change in thickness due to the growth can significantly affect buckling, both in terms of the critical pressure and the buckling pattern. Finally, the effects of the thickness ratio A1/A2, mode number n, and the growth parameter γ are studied on the shell’s stability.

Curvature induces active velocity waves in rotating spherical tissues

The multicellular organization of diverse systems, including embryos, intestines, and tumors relies on coordinated cell migration in curved environments. In these settings, cells establish supracellular patterns of motion, including collective rotation and invasion. While such collective modes have been studied extensively in flat systems, the consequences of geometrical and topological constraints on collective migration in curved systems are largely unknown. Here, we discover a collective mode of cell migration in rotating spherical tissues manifesting as a propagating single-wavelength velocity wave. This wave is accompanied by an apparently incompressible supracellular flow pattern featuring topological defects as dictated by the spherical topology. Using a minimal active particle model, we reveal that this collective mode arises from the effect of curvature on the active flocking behavior of a cell layer confined to a spherical surface. Our results thus identify curvature-induced velocity waves as a mode of collective cell migration, impacting the dynamical organization of 3D curved tissues.

Heat Transfer in Biological Spherical Tissues during Hyperthermia of Magnetoma.

Simple SummaryHeat transport in biological tissue is mediated through a variety of phenomenological processes, involving tissue heat exchange, blood-tissue convection, blood perfusion or advection and diffusion across microvascular beds, and metabolic heat production. In recent years, many physicians and engineers have taken an interest in applying computational and mathematical techniques to model biological systems. The objective of the current paper is to provide an analytical solution to the modified Pennes bioheat conduction equation with a single relaxation time. The suggested model is used to examine heat transport in biological tissues as an infinite concentric spherical region during magnetic fluid hyperthermia. This method is used to investigate the influence of heat generation through heat treatment on a skin tumor a spherical layered structure. The present model can explain the effect of different therapeutic approaches such as cryotherapy sessions, laser therapy, and physical occurrences including transfer, metabolism support, blood perfusion, and other similar treatments.Hyperthermia therapy is now being used to treat cancer. However, understanding the pattern of temperature increase in biological tissues during hyperthermia treatment is essential. In recent years, many physicians and engineers have studied the use of computational and mathematical models of heat transfer in biological systems. The rapid progress in computing technology has intrigued many researchers. Many medical procedures also use engineering techniques and mathematical modeling to ensure their safety and assess the risks involved. One such model is the modified Pennes bioheat conduction equation. This paper provides an analytical solution to the modified Pennes bioheat conduction equation with a single relaxation time by incorporating in it the (MGT) equation. The suggested model examines heat transport in biological tissues as forming an infinite concentric spherical region during magnetic fluid hyperthermia. To investigate thermal reactions caused by temperature shock, specifically the influence of heat generation through heat treatment on a skin tumor [AEGP9], the Laplace transformation, and numerical inverse transformation methods are used. This model was able to explain the effects of different therapeutic approaches such as cryotherapy sessions, laser therapy, and physical occurrences, transfer, metabolism support, and blood perfusion. Comparison of the numerical results of the suggested model with those in the literature confirmed the validity of the model’s numerical results.

Finite element analyses of nonlinear DPL bioheat model in spherical tissues using experimental data

Based on the non-linear dual phase lag model, the present investigation treats with mathematical models of bioheat transfer to study the transient phenomena in a spherical tissue due to the effect of laser heat source. Caused by the nonlinear basic equations, the finite element method is adopted to get the solutions of this problem. To verify the accuracy of the numerical solutions, the numerical results obtained by the finite element method are compared with the experimental data. Also, the comparison between the experimental results and the numerical results display that the existing mathematical model is efficacious tool to estimate the bio-heat model in the spherical biological tissues.

Analytical solutions of fractional bioheat model in a spherical tissue

In this paper, the bio-heat model with fractional derivative is established to study the variations of temperature and the thermal damage in spherical tissues during thermal therapy. Easily, the exact solution in the domain of Laplace are obtained. The effects of a fractional parameter, the blood perfusion and the laser exposure time on the temperature of living tissue and the resulting of thermal damages are studied. The results display that bio-heat model with the fractional derivative is reduced to parabolic and the hyperbolic bio-heat models when the thermal relaxation time is equal to zero and the fractional parameter is equivalent to one respectively. The numerical outcomes of thermal damage and temperatures are graphically introduced.

Therapeutic potential of spheroids of stem cells from human exfoliated deciduous teeth for chronic liver fibrosis and hemophilia A.

Mesenchymal stem cell (MSC)-based cell therapies have emerged as a promising treatment option for various diseases. Due to the superior survival and higher differentiation efficiency, three-dimensional spheroid culture systems have been an important topic of MSC research. Stem cells from human exfoliated deciduous teeth (SHED) have been considered an ideal source of MSCs for regenerative medicine. Thus, in the present study, we introduce our newly developed method for fabricating SHED-based micro-hepatic tissues, and demonstrate the therapeutic effects of SHED-based micro-hepatic tissues in mouse disease models. SHED-converted hepatocyte-like cells (SHED-HLCs) were used for fabricating spherical micro-hepatic tissues. The SHED-HLC-based spheroids were then transplanted both into the liver of mice with CCl4-induced chronic liver fibrosis and the kidney of factor VIII (F8)-knock-out mice. At 4weeks after transplantation, the therapeutic efficacy was investigated. Intrahepatic transplantation of SHED-HLC-spheroids improved the liver dysfunction in association with anti-fibrosis effects in CCl4-treated mice. Transplanted SHED-converted cells were successfully engrafted in the recipient liver. Meanwhile, renal capsular transplantation of the SHED-HLC-spheroids significantly extended the bleeding time in F8-knock-out mice. These findings suggest that SHED-HLC-based micro-hepatic tissues might be a promising source for treating pediatric refractory diseases, including chronic liver fibrosis and hemophilia A.

Genesis of ultra-specialized histology with stable traits in mesophyll of drought tolerant apple cultivars

Even if some biological defense responses are activated instantaneously after stress occurrence, but other mechanisms of drought tolerance could be probed, detected and diagnosed as sable traits at mesophyll level. The present observations demonstrated multilateral modifications in different leaf parts, specialized parenchyma tissues and cribro-vascular bundles that facilitate vital activities in tolerant apple cultivars. In 2006, long deficit irrigation occurred in commercial apple collection containing 93 cultivars located in Karaj-Iran. Entire bearing 16-Year-old trees lost completely the crop except 16 CVs which were assessed for yield per tree since June drop to physiological maturity. Based on thehypothesis, stable traits were developed against drought stress through phenomenon of genesis. 19 different anatomical traits of mesophyll were accurately assessed in the selected resistant CVs compared with the susceptible "Golden Delicious" and native "Assali" as the controls. Microscopic studies computed on the transversal sections of mesophyll prepared by microtome ascertained ultra-specialized histological traits in the selected CVs. Morphologically, basal part of the main vein was completely spherical, outfitted, highly ordered and tidy tissues. Epidermis underlying layer was composed of well-organized tissues containing uniform cells by shape and size, inserted consistently next to one another in neat order with no intercellular space. Contrarily, controls showed opposite rhythm in all examined characters. Also, the mean number of epidermis layers at leaf margin resulted higher related to susceptible CVs. The mean number of vascular bundles and stomata decreased in tolerant CVs. These observations put in evidence some stable ultra-specialized histological traits of mesophyll, as a result of genesis route.

Optimization of detection device geometry for NIR spectroscopy using a three-layered model of stone fruit

The influences of detection device geometry and fiber optic parameters on near infrared spectroscopy measurements were assessed using stone fruit models based on Monte Carlo simulation. The stone fruit was modeled as concentric spherical layered tissues including the skin, the flesh and the core. The choices of the detection angle, the diameter of the detection fiber, the numerical aperture, and the height of the probe were discussed. Receiving diffuse reflectance signals at detection angles in the range of 35°–50° and normalizing the detection signals by the collection area and the solid acceptance angle prior to use are suggested. Fiber probes with diameters D = 0.06 cm or 0.1 cm, NA = 0.20 or 0.30, and height h ≤ 0.8 cm are preferred. The probe deflection angle should be limited to within ±5° to guarantee measurement accuracy.

Engineering tissues with a perfusable vessel-like network using endothelialized alginate hydrogel fiber and spheroid-enclosing microcapsules.

Development of the technique for constructing an internal perfusable vascular network is a challenging issue in fabrication of dense three-dimensional tissues in vitro. Here, we report a method for realizing it. We assembled small tissue (about 200 μm in diameter)-enclosing hydrogel microcapsules and a single hydrogel fiber, both covered with human vascular endothelial cells in a collagen gel. The microcapsules and fiber were made from alginate and gelatin derivatives, and had cell adhesive surfaces. The endothelial cells on the hydrogel constructs sprouted and spontaneously formed a network connecting the hydrogel constructs with each other in the collagen gel. Perfusable vascular network-like structure formation after degrading the alginate-based hydrogel constructs by alginate lyase was confirmed by introducing solution containing tracer particles of about 3 μm in diameter into the lumen templated by the alginate hydrogel fiber. The introduced solution flowed into the spontaneously formed capillary branches and passed around the individual spherical tissues.

Production of hyaluronic‐acid‐based cell‐enclosing microparticles and microcapsules via enzymatic reaction using a microfluidic system

ABSTRACTThis article describes the preparation of cell‐enclosing hyaluronic acid (HA) microparticles with solid core and microcapsules with liquid core through cell‐friendly horseradish peroxidase (HRP)‐catalyzed hydrogelation. The spherical vehicles were made from HA derivative possessing phenolic hydroxyl moieties (HA‐Ph) cross‐linkable through the enzymatic reaction by extruding cell‐suspending HA‐Ph aqueous solution containing HRP from a needle of 180 μm in inner diameter into the ambient coaxial flow of liquid paraffin containing H2O2 in a microtubule of 600 μm in diameter. By altering the flow rate of liquid paraffin, the diameters of gelatin and HA‐Ph microparticles were varied in the range of 120–220 μm and 100–300 μm, respectively. The viability of the enclosed human hepatoma HepG2 cells in the HA‐Ph microparticles of 180 μm in diameter was 94.2 ± 2.3%. The growth of the enclosed HepG2 cells was enhanced by decreasing the HRP concentration. The microcapsules of 200 μm in diameter were obtained by extruding HA‐Ph aqueous solution containing thermally liquefiable cell‐enclosing gelatin microparticles of 150 μm in diameter using the same microfluidic system. The enclosed cells grew and filled the cavity within 10 days. Spherical tissues covered with a heterogeneous cell layer were obtained by degrading the microcapsule membrane using hyaluronidase after covering the surface with a heterogeneous cell layer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43107.

Bioheat transfer problem for one-dimensional spherical biological tissues

Based on the Pennes bioheat transfer equation with constant blood perfusion, we set up a simplified one-dimensional bioheat transfer model of the spherical living biological tissues for application in bioheat transfer problems. Using the method of separation of variables, we present in a simple way the analytical solution of the problem. The obtained exact solution is used to investigate the effects of tissue properties, the cooling medium temperature, and the point-heating on the temperature distribution in living bodies. The obtained analytical solution can be useful for investigating thermal behavior research of biological system, thermal parameter measurements, temperature field reconstruction and clinical treatment.

Impact of the composition of alginate and gelatin derivatives in bioconjugated hydrogels on the fabrication of cell sheets and spherical tissues with living cell sheaths

Gelatin and alginate derivatives possessing phenolic hydroxyl moieties (gelatin–Ph and Alg–Ph) were dissolved in aqueous solution and conjugated via horseradish peroxidase-catalyzed crosslinking, resulting in hydrogelation. The objective of creating the hydrogels was to prepare cell sheets and spherical tissues wrapped in living cell sheaths. An increase in the gelatin–Ph content in the hydrogel improved cellular adhesion on the hydrogel surface but hindered degradability by alginate lyase. A hydrogel with the desired characteristics was obtained from a solution containing 0.5% (w/v) gelatin–Ph and 1.5% (w/v) Alg–Ph. Human aortic endothelial (HAE) cells and mouse embryo fibroblast 10T1/2 cells grew on the hydrogels and could be harvested as cell sheets by treatment with alginate lyase. 10T1/2 cells enclosed in Alg–Ph/gelatin–Ph microcapsules composed of the conjugate hydrogel elongated on the inner surface of the microcapsules and grew three times faster than those enclosed in Alg–Ph microcapsules. Alg–Ph/gelatin–Ph microcapsules not only supported growth of the enclosed cells into spherical tissues, but also provided a cell adhesive outer surface for the fabrication of an HAE cell layer. Finally, spherical tissues of 10T1/2 cells wrapped in living HAE cell sheaths were obtained by treatment with alginate lyase.

Rapidly serum‐degradable hydrogel templating fabrication of spherical tissues and curved tubular structures

Development of the techniques for fabricating three-dimensional tissues still poses significant challenges for tissue engineering. We used hydrogels obtained from phenol-substituted amylopectin (AP-Ph) as templates for preparing multicellular spherical tissues (MSTs) and endothelialized curved tubular structures in type I collagen gel. AP-Ph hydrogel microparticles of diameter 200 µm and fibers of diameter 500 µm disappeared within hours of soaking in a serum-containing medium. HeLa cells and human endothelial cells were enclosed in the microparticles and hydrogel fibers, respectively, and then embedded in Ca-alginate microcapsules or the collagen gel. The enclosed cells were released in cavities formed by hydrogel degradation in the serum-containing medium. The released HeLa cells in the spherical cavities grew and formed MSTs, eventually filling the cavities. The spherical tissues were easily harvested by liquefying the Ca-alginate hydrogel microcapsule membrane by chelation using sodium citrate. The released endothelial cells grew on the tubular cavity surfaces and formed tubular structures. An endothelial cell network was formed by cell migration into the collagen gel. These results demonstrate the potential of serum-degradable AP-Ph hydrogels in constructing three-dimensional tissues.

Cell-enclosing gelatin-based microcapsule production for tissue engineering using a microfluidic flow-focusing system

Gelatin-based microcapsule production using a microfluidic system and the feasibility of the resultant microcapsules for constructing spherical tissues surrounded by heterogeneous cells were studied. The first cell-encapsulation and subsequent cell-enclosing microparticle encapsulation were achieved using a microfluidic flow-focusing droplet production system. A hollow-core structure of about 150 μm in diameter was developed by incubating the resultant microparticles at 37 °C, which induced thermal melting of the enclosed unmodified gelatin microparticles. Mammalian cells filled the hollow-cores after 4 days of incubation. A cell layer on the cell-enclosing microcapsules was developed by simply suspending the microcapsules in medium containing adherent fibroblast cells. This method may prove useful for the generation of gelatin microcapsules using a microfluidic system for formation of artificial tissue constructs.

Chondrocyte distribution and cartilage regeneration in silk fibroin sponge

Chondrocytes distribution and cartilage formation in three types of fibroin sponges with different average pore sizes (40-80, 80-120 and 100-140 μm) was measured. The image processing was performed combining two methods to identify cells automatically: extraction of local maximum luminance and multi-threshold analysis. The results showed that initial accumulation of chondrocytes localized at surface area at 3 h in the small and medium-pore groups, however, the difference in the cell distributions become equivalent until 24 h after seeding. Cartilaginous tissue was well formed in each group at 21 days, and that in the smaller pore group tend to distribute at the surface area. Spherical tissues were located at the subsurface (200-600 μm below the surface) of the sponge in the medium- and large-pore groups at 21 days. Local cell aggregation was observed at 24 h at the same depth of the fibroin sponge as the spherical tissues observed at 21 days. These results suggest that the initial cell condensation process till 24 h after seeding play an important role in cartilage tissue formation.

Simulation of elastic wave scattering in cells and tissues at the microscopic level

The scattering of longitudinal and shear waves from spherical, nucleated cells and three-dimensional tissues with simple and hierarchical microstructures was numerically modeled at the microscopic level using an iterative multipole approach. The cells were modeled with a concentric core-shell (nucleus-cytoplasm) structure embedded in an extracellular matrix. Using vector multipole expansions and boundary conditions, scattering solutions were derived for single cells with either solid or fluid properties for each of the cell components. Tissues were modeled as structured packings of cells. Multiple scattering between cells was simulated using addition theorems to translate the multipole fields from cell to cell in an iterative process. Backscattering simulations of single cells indicated that changes in the shear properties and nuclear diameter had the greatest effect on the frequency spectra. Simulated wave field images and high-frequency spectra (15-75 MHz) from tissues containing 1211-2137 cells exhibited up to 20% enhancement of the field amplitudes at the plasma membrane, significant changes in spectral features due to neoplastic and other microstructural alterations, and a detection threshold of approximately 8.5% infiltration of tumor cells into normal tissue. These findings suggest that histology-based simulations may provide insight into fundamental ultrasound-tissue interactions and help in the development of new medical technologies.

Production of cell‐enclosing hollow‐core agarose microcapsules via jetting in water‐immiscible liquid paraffin and formation of embryoid body‐like spherical tissues from mouse ES cells enclosed within these microcapsules

We developed agarose microcapsules with a single hollow core templated by alginate microparticles using a jet-technique. We extruded an agarose aqueous solution containing suspended alginate microparticles into a coflowing stream of liquid paraffin and controlled the diameter of the agarose microparticles by changing the flow rate of the liquid paraffin. Subsequent degradation of the inner alginate microparticles using alginate lyase resulted in the hollow-core structure. We successfully obtained agarose microcapsules with 20-50 microm of agarose gel layer thickness and hollow cores ranging in diameter from ca. 50 to 450 microm. Using alginate microparticles of ca. 150 microm in diameter and enclosing feline kidney cells, we were able to create cell-enclosing agarose microcapsules with a hollow core of ca. 150 microm in diameter. The cells in these microcapsules grew much faster than those in alginate microparticles. In addition, we enclosed mouse embryonic stem cells in agarose microcapsules. The embryonic stem cells began to self-aggregate in the core just after encapsulation, and subsequently grew and formed embryoid body-like spherical tissues in the hollow core of the microcapsules. These results show that our novel microcapsule production technique and the resultant microcapsules have potential for tissue engineering, cell therapy and biopharmaceutical applications.

セメント質腫の臨床的病理組織学的検索 根尖性セメント質異形成症ならびにセメント質の塊状増殖病変について

Although cementoma is one of the odontogenic tumors, its pathological features are complicated and sometimes difficult to distinguish from bone diseases. So it is categorized as a fibro-osseous lesion. According to the WHO classification, it is classified into four lesions. However we sometimes encounter the lesions of a mass composed only of the cementum which is not described in above classification.In the present report, we studied 9 cases of periapical cemental dysplasia and 13 cases of massive lesion which we had experienced in our department.Both lesions occured in middle-aged and old women and ivolved mandibular molar regions. Radiologically, they appeared as well defined opaque figures circumscribed by thin lucent zones. The lesions located in the periapical regions were smaller than those located in the edentulous regions. Periapical cemental dysplasias produced various combinations of trabecular, spherical hard tissues and they fused to become large masses. Various stages of maturation could be seen in each hard tissue. Massive cemental lesions affected older patients more often than the periapical cemental dysplasias. Histologically, the lesion consisted of a large cemental mass, resembling mature bone. Most of the lesions were infected and associated with abscess.We found a process of development from periapical cemental dysplasia to massive cemental lesions, but there still remain many problems before concluding that the latter lesion is the mature inactive stage of the former lesion.