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Computational Biophysics and Imaging Group

Publications

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Professor Hyttinen at Google Scholar

2026

2025

2024

2023

2022

2021

  • Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity

    Brain organoids are in vitro three-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10-20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly...

  • Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron-Astrocyte Co-Cultures

    Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer's disease, and Parkinson's disease. Convulsant drugs such as...

  • A mathematical model of hiPSC cardiomyocytes electromechanics

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming instrumental in cardiac research, human-based cell level cardiotoxicity tests, and developing patient-specific care. As one of the principal functional readouts is contractility, we propose a novel electromechanical hiPSC-CM computational model named the hiPSC-CM-CE. This model comprises a reparametrized version of contractile element (CE) by Rice et al., 2008, with a new passive force formulation, integrated...

  • Optical projection tomography as a quantitative tool for analysis of cell morphology and density in 3D hydrogels

    Assessing cell morphology and function, as well as biomaterial performance in cell cultures, is one of the key challenges in cell biology and tissue engineering (TE) research. In TE, there is an urgent need for methods to image actual three-dimensional (3D) cell cultures and access the living cells. This is difficult using established optical microscopy techniques such as wide-field or confocal microscopy. To address the problem, we have developed a new protocol using Optical Projection...

  • Iron Transporter Protein Expressions in Children with Celiac Disease

    Anemia is a frequent finding in children with celiac disease but the detailed pathophysiological mechanisms in the intestine remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been inconsistent. We investigated this issue by comparing immunohistochemical stainings of duodenal cytochrome B (DCYTB), divalent metal transporter 1 (DMT1), ferroportin, hephaestin and transferrin receptor 1 (TfR1) in duodenal...

2020

2019

  • 3D Scaffolds of Polycaprolactone/Copper-Doped Bioactive Glass: Architecture Engineering with Additive Manufacturing and Cellular Assessments in a Coculture of Bone Marrow Stem Cells and Endothelial Cells

    The local delivery of Cu^(2+) from copper-doped bioactive glass (Cu-BaG) was combined with 3D printing of polycaprolactone (PCL) scaffolds for its potent angiogenic effect in bone tissue engineering. PCL and Cu-BaG were, respectively, dissolved and dispersed in acetone to formulate a moderately homogeneous ink. The PCL/Cu-BaG scaffolds were fabricated via direct ink writing into a cold ethanol bath. The architecture of the printed scaffolds, including strut diameter, strut spacing, and porosity,...

  • A Computational Model of Interactions Between Neuronal and Astrocytic Networks: The Role of Astrocytes in the Stability of the Neuronal Firing Rate

    Recent research in neuroscience indicates the importance of tripartite synapses and gliotransmission mediated by astrocytes in neuronal system modulation. Although the astrocyte and neuronal network functions are interrelated, they are fundamentally different in their signaling patterns and, possibly, the time scales at which they operate. However, the exact nature of gliotransmission and the effect of the tripartite synapse function at the network level are currently elusive. In this paper, we...

  • A device for measuring sternal bone connectivity using vibration analysis techniques

    CONCLUSION: Technical solutions and description of validation process were given. The device was calibrated, and the vibration transmittance analysis differentiated intact and cut polylactide rod. In the sternum, intact bone, wire fixation with exact apposition, and with a gap were identified separately. Although further studies are needed to assess the accuracy of the method to detect different levels of diastases, the method appears to be feasible.

  • Gaussian Light Model in Brightfield Optical Projection Tomography

    This study focuses on improving the reconstruction process of the brightfield optical projection tomography (OPT). OPT is often described as the optical equivalent of X-ray computed tomography, but based on visible light. The detection optics used to collect light in OPT focus on a certain distance and induce blurring in those features out of focus. However, the conventionally used inverse Radon transform assumes an absolute focus throughout the propagation axis. In this study, we model the...

  • Automatic classification of IgA endomysial antibody test for celiac disease: a new method deploying machine learning

    Widespread use of endomysial autoantibody (EmA) test in diagnostics of celiac disease is limited due to its subjectivity and its requirement of an expert evaluator. The study aimed to determine whether machine learning can be applied to create a new observer-independent method of automatic assessment and classification of the EmA test for celiac disease. The study material comprised of 2597 high-quality IgA-class EmA images collected in 2017-2018. According to standard procedure,...

  • Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation

    Electricity is important in the physiology and development of human tissues such as embryonic and fetal development, and tissue regeneration for wound healing. Accordingly, electrical stimulation (ES) is increasingly being applied to influence cell behavior and function for a biomimetic approach to in vitro cell culture and tissue engineering. Here, the application of conductive polymer (CP) poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillars is described, direct-write...

  • Mechanically Biomimetic Gelatin-Gellan Gum Hydrogels for 3D Culture of Beating Human Cardiomyocytes

    To promote the transition of cell cultures from 2D to 3D, hydrogels are needed to biomimic the extracellular matrix (ECM). One potential material for this purpose is gellan gum (GG), a biocompatible and mechanically tunable hydrogel. However, GG alone does not provide attachment sites for cells to thrive in 3D. One option for biofunctionalization is the introduction of gelatin, a derivative of the abundant ECM protein collagen. Unfortunately, gelatin lacks cross-linking moieties, making the...

  • Advances in Human Stem Cell-Derived Neuronal Cell Culturing and Analysis

    This chapter provides an overview of the current stage of human in vitro functional neuronal cultures, their biological application areas, and modalities to analyze their behavior. During the last 10 years, this research area has changed from being practically non-existent to one that is facing high expectations. Here, we present a case study as a comprehensive short history of this process based on extensive studies conducted at NeuroGroup (University of Tampere) and Computational Biophysics...

  • Viability of Mouse Retinal Explant Cultures Assessed by Preservation of Functionality and Morphology

    CONCLUSIONS: Retinal explants provide a valuable tool for studies of retinal functions and development of ocular therapies. However, critical for long-term use, retinal functionality was lost before structural loss, emphasizing a need for both functional and morphologic readouts to determine the overall state of the cultured retina.

  • Do bone geometric properties of the proximal femoral diaphysis reflect loading history, muscle properties, or body dimensions?

    CONCLUSIONS: Activity effects from ground impact loading were associated with higher bone geometric values, especially at the femur mid-shaft, but also at lesser and sub-trochanter cross-sections. Bone geometric properties along the femur can be used to assess the mechanical stimuli experienced, where ground impact loading seems to be more important than muscle loading.

  • Structural dynamics of tight junctions modulate the properties of the epithelial barrier

    Tight junctions are dynamic structures that are crucial in establishing the diffusion and electrical barrier of epithelial monolayers. Dysfunctions in the tight junctions can impede this barrier function and lead to many pathological conditions. Unfortunately, detailed understanding of the non-specific permeation pathway through the tight junctions, the so-called leak pathway, is lacking. We created computational models of the leak pathway to describe the two main barrier measures, molecular...

  • Bioactive glass ions induce efficient osteogenic differentiation of human adipose stem cells encapsulated in gellan gum and collagen type I hydrogels

    CONCLUSIONS: Overall, we showed efficacious osteogenesis of hASCs in 3D hydrogels with BaG OM with potential for bone-like grafts.

  • A mathematical model and iterative inversion for fluorescent optical projection tomography

    Solving the fluorophore distribution in a tomographic setting has been difficult because of the lack of physically meaningful and computationally applicable propagation models. This study concentrates on the direct modelling of fluorescence signals in optical projection tomography (OPT), and on the corresponding inverse problem. The reconstruction problem is solved using emission projections corresponding to a series of rotational imaging positions of the sample. Similarly to the bright field...

  • Vibration transmittance measures sternotomy stability - a preliminary study in human cadavers

    CONCLUSIONS: Vibration transmittance analysis differentiates the intact sternum, wire fixation with exact apposition, and wire fixation with a gap. The gap detection capability is not dependent on the tested costal level. The method may prove useful in the early detection of sternal instability and warrants further exploration.

  • Real-Time Bioimpedance-Based Biopsy Needle Can Identify Tissue Type with High Spatial Accuracy

    Histological analysis is meaningful in diagnosis only if the targeted tissue is obtained in the biopsy. Often, physicians have to take a tissue sample without accurate information about the location of the instrument tip. A novel biopsy needle with bioimpedance-based tissue identification has been developed to provide data for the automatic classification of the tissue type at the tip of the needle. The aim of this study was to examine the resolution of this identification method and to assess...

2018

  • Real-Time Bioimpedance-Based Biopsy Needle Can Identify Tissue Type with High Spatial Accuracy

    Histological analysis is meaningful in diagnosis only if the targeted tissue is obtained in the biopsy. Often, physicians have to take a tissue sample without accurate information about the location of the instrument tip. A novel biopsy needle with bioimpedance-based tissue identification has been developed to provide data for the automatic classification of the tissue type at the tip of the needle. The aim of this study was to examine the resolution of this identification method and to assess...

  • Large-Scale Simulation of the Phenotypical Variability Induced by Loss-of-Function Long QT Mutations in Human Induced Pluripotent Stem Cell Cardiomyocytes

    Loss-of-function long QT (LQT) mutations inducing LQT1 and LQT2 syndromes have been successfully translated to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) used as disease-specific models. However, their in vitro investigation mainly relies on experiments using small numbers of cells. This is especially critical when working with cells as heterogeneous as hiPSC-CMs. We aim (i) to investigate in silico the ionic mechanisms underlying LQT1 and LQT2 hiPSC-CM phenotypic...

  • Functional Voltage-Gated Calcium Channels Are Present in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium

    Retinal pigment epithelium (RPE) performs important functions for the maintenance of photoreceptors and vision. Malfunctions within the RPE are implicated in several retinal diseases for which transplantations of stem cell-derived RPE are promising treatment options. Their success, however, is largely dependent on the functionality of the transplanted cells. This requires correct cellular physiology, which is highly influenced by the various ion channels of RPE, including voltage-gated Ca^(2+)...

  • Novel osteoconductive β-tricalcium phosphate/poly(L-lactide-co-e-caprolactone) scaffold for bone regeneration: a study in a rabbit calvarial defect

    The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO(2) -processed porous composite scaffold of β-tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical size calvarial defects were...

  • Porous poly-l-lactide-co-ɛ-caprolactone scaffold: a novel biomaterial for vaginal tissue engineering

    The surgical reconstruction of functional neovagina is challenging and susceptible to complications. Therefore, developing tissue engineering-based treatment methods for vaginal defects is important. Our aim was to develop and test a novel supercritical carbon dioxide foamed poly-l-lactide-co-ɛ-caprolactone (scPLCL) scaffold for vaginal reconstruction. The scaffolds were manufactured and characterized for porosity (65 ± 4%), pore size (350 ± 150 µm) and elastic modulus (2.8 ± 0.4 MPa). Vaginal...

  • Wound healing of human embryonic stem cell-derived retinal pigment epithelial cells is affected by maturation stage

    CONCLUSIONS: This acquired knowledge about Ca^(2+) dynamics of wounded hESC-RPE monolayers is important for understanding the dynamics of RPE wound healing, and could offer a reliable functionality test for RPE cells. The data presented in here suggests that assessment of Ca^(2+) dynamics analysed with image analysis could be used as a reliable non-invasive functionality test for RPE cells.

  • Automatic Optimization of an <em>in Silico</em> Model of Human iPSC Derived Cardiomyocytes Recapitulating Calcium Handling Abnormalities

    The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca^(2+) handling. We used (i) the hiPSC-CM...

  • Impact loading history modulates hip fracture load and location: A finite element simulation study of the proximal femur in female athletes

    Sideways falls impose high stress on the thin superolateral cortical bone of the femoral neck, the region regarded as a fracture-prone region of the hip. Exercise training is a natural mode of mechanical loading to make bone more robust. Exercise-induced adaptation of cortical bone along the femoral neck has been previously demonstrated. However, it is unknown whether this adaption modulates hip fracture behavior. The purpose of this study was to investigate the influence of specific exercise...

  • Knitted 3D Scaffolds of Polybutylene Succinate Support Human Mesenchymal Stem Cell Growth and Osteogenesis

    Polybutylene succinate (PBS) is a biodegradable polyester with better processability and different mechanical properties compared to polylactides (PLAs), the most commonly used synthetic polymers in tissue engineering (TE). Since only few studies have evaluated PBS-containing materials for bone TE, we prepared PLA-PBS blends and analyzed material properties as well as cell attachment, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) on scaffolds. In addition...

  • A Portable Microscale Cell Culture System with Indirect Temperature Control

    A physiologically relevant environment is essential for successful long-term cell culturing in vitro. Precise control of temperature, one of the most crucial environmental parameters in cell cultures, increases the fidelity and repeatability of the experiments. Unfortunately, direct temperature measurement can interfere with the cultures or prevent imaging of the cells. Furthermore, the assessment of dynamic temperature variations in the cell culture area is challenging with the methods...

  • Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death

    Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of...

  • Ricci-flow based conformal mapping of the proximal femur to identify exercise loading effects

    The causal relationship between habitual loading and adaptive response in bone morphology is commonly explored by analysing the spatial distribution of mechanically relevant features. In this study, 3D distribution of features in the proximal femur of 91 female athletes (5 exercise loading groups representing habitual loading) is contrasted with 20 controls. A femur specific Ricci-flow based conformal mapping procedure was developed for establishing correspondence among the periosteal surfaces....

  • Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

    Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human...