Building blocks of microphysiological system to model physiology and pathophysiology of human heart

Microphysiological systems (MPS) are drawing increasing interest from academia and from biomedical industry due to their improved capability to capture human physiology. MPS offer an advanced in vitro platform that can be used to study human organ and tissue level functions in health and in diseased states more accurately than traditional single cell cultures or even animal models. Key features in MPS include microenvironmental control and monitoring as well as high biological complexity of the target tissue. To reach these qualities, cross-disciplinary collaboration from multiple fields of science is required to build MPS. Here, we review different areas of expertise and describe essential building blocks of heart MPS including relevant cardiac cell types, supporting matrix, mechanical stimulation, functional measurements, and computational modelling. The review presents current methods in cardiac MPS and provides insights for future MPS development with improved recapitulation of human physiology.Peer reviewe

Hyaluronic acid based next generation bioink for 3D bioprinting of human stem cell derived corneal stromal model with innervation

Corneal transplantation remains gold standard for the treatment of severe cornea diseases, however, scarcity of donor cornea is a serious bottleneck. 3D bioprinting holds tremendous potential for cornea tissue engineering (TE). One of the key technological challenges is to design bioink compositions with ideal printability and cytocompatibility. Photo-crosslinking and ionic crosslinking are often used for the stabilization of 3D bioprinted structures, which can possess limitations on biological functionality of the printed cells. Here, we developed a hyaluronic acid-based dopamine containing bioink using hydrazone crosslinking chemistry for the 3D bioprinting of corneal equivalents. First, the shear thinning property, viscosity, and mechanical stability of the bioink were optimized before extrusion-based 3D bioprinting for the shape fidelity and self-healing property characterizations. Subsequently, human adipose stem cells (hASCs) and hASC-derived corneal stromal keratocytes were used for bioprinting corneal stroma structures and their cell viability, proliferation, microstructure and expression of key proteins (lumican, vimentin, connexin 43,α-smooth muscle actin) were evaluated. Moreover, 3D bioprinted stromal structures were implanted intoex vivoporcine cornea to explore tissue integration. Finally, human pluripotent stem cell derived neurons (hPSC-neurons), were 3D bioprinted to the periphery of the corneal structures to analyze innervation. The bioink showed excellent shear thinning property, viscosity, printability, shape fidelity and self-healing properties with high cytocompatibility. Cells in the printed structures displayed good tissue formation and 3D bioprinted cornea structures demonstrated excellentex vivointegration to host tissue as well asin vitroinnervation. The developed bioink and the printed cornea stromal equivalents hold great potential for cornea TE applications.publishedVersionPeer reviewe

Voima- ja tasapainoryhmän toimintamallin kehittäminen Heinolan terveyskeskuksessa

Opinnäytetyön tarkoituksena oli kehittää Heinolan terveyskeskuksessa toimivan voima- ja tasapainoryhmän toimintaa. Tavoitteena oli luoda ryhmätoiminnalle selkeä ja tutkimustiedon perusteella vaikuttava toimintamalli, joka sisältää toiminnan vaiheet aina ryhmäarviokäynnistä loppumittauksiin. Kirjallisuuden perusteella alku- ja loppumittauksiin valittiin lihasvoimaa ja tasapainoa mittaavia luotettavia ja toistettavia testejä (n=7), kuten yhden jalan seisonta, 10 metrin kävelytesti ja toistomaksimitestejä. Ryhmäläisiä oli seitsemän ja he olivat kaikki ikääntyneitä. Alkutestauksien perusteella jokaiselle ryhmäläiselle laadittiin yksilöllinen harjoitteluohjelma ja kotiharjoitteet. Kotiharjoittelun toteutumista seurattiin harjoittelupäiväkirjan avulla. Ryhmä kokoontui kerran viikossa kymmenen viikon ajan, minkä jälkeen ryhmäläisille suoritettiin loppumittaus. Toimintamallin toimivuutta arvioitiin alku- ja loppumittauksien tuloksia vertaamalla sekä kysymällä palautetta luodusta toimintamallista sekä ryhmäläisiltä, että ohjaajilta. Kymmenen viikon harjoittelujakson aikana suurimmat muutokset mittaustuloksissa tapahtuivat lihasvoiman parantumisessa. Ryhmäläiset kokivat harjoitteet sopivina ja ryhmän palvelleen omia tarpeitaan. Ohjaajien mielestä testit olivat monipuolisia ja käyttökelpoisia, mutta kokivat haasteellisena mallin siirtämisen käytäntöön rajallisten resurssien takia. Kehitetty toimintamalli soveltuu käytännössä tämäntyyppisen voima- ja tasapainoryhmän käyttöön. Testauksiin valituilla testeillä pystyttiin mittaamaan voimaa ja tasapainoa ja niissä tapahtuneita muutoksia. Ryhmäläisten ja ohjaajien mielipiteet mallista tukivat sen käyttökelpoisuutta. Kehitettyä ryhmätoimintamallia voidaan jatkossa käyttää samantyyppisen ryhmän toiminnassa ja ryhmätoiminnan kehittämisessä. Toimintamallia voidaan helposti myös soveltaa ryhmän erityistarpeiden mukaan.The purpose of the bachelor's thesis was to develop the activities of a strength and balance group operating at the Health Center of Heinola. The aim was to create a simple and reliable operating model based on research knowledge, including every step from the group assessment visit to the final testing. Based on literature, reliable and valid tests (n=7) measuring muscle strength and balance were selected for the initial and final testing. The tests included standing on one leg, a ten meter walk test and repetition maximum tests. There were seven elderly people in the group. On the basis of the initial testing, a personal training programme and a home training programme were designed for each member of the group. Home training was controlled with help a training diary. The group convened once a week for ten weeks. After the training period the final testing was carried out. The functionality of the operating model was evaluated by comparing the results between the initial and final testing and by collecting feedback from the members and the supervisors of the group. The improvement of muscle strength was the major change in the test results during the ten week-long training period. The members of the group felt that the exercises had been appropriate and the group had served their personal needs. The supervisors saw the tests as versatile and useful. However, they found it challenging to implement the model due to limited resources. The developed operating model is suitable for a similar type of strength and balance group. The selected tests made it possible to measure strength and balance and changes in them. The opinions of the members and the supervisors of the group supported the functionality of the model. In the future the developed operating model can be used for group activities and for further development of the activities. It is also possible to apply and adjust the operating model according to the special needs of each group

Novel method to produce a layered 3D scaffold for human pluripotent stem cell-derived neuronal cells

BACKGROUND: Three-dimensional (3D) in vitro models have been developed into more in vivo resembling structures. In particular, there is a need for human-based models for neuronal tissue engineering (TE). To produce such a model with organized microenvironment for cells in central nervous system (CNS), a 3D layered scaffold composed of hydrogel and cell guiding fibers has been proposed. NEW METHOD: Here, we describe a novel method for producing a layered 3D scaffold consisting of electrospun poly (L,D-lactide) fibers embedded into collagen 1 hydrogel to achieve better resemblance of cells' natural microenvironment for human pluripotent stem cell (hPSC)-derived neurons. The scaffold was constructed via a single layer-by-layer process using an electrospinning technique with a unique collector design. RESULTS: The method enabled the production of layered 3D cell-containing scaffold in a single process. HPSC-derived neurons were found in all layers of the scaffold and exhibited a typical neuronal phenotype. The guiding fiber layers supported the directed cell growth and extension of the neurites inside the scaffold without additional functionalization. COMPARISON WITH EXISTING METHODS: Previous methods have required several process steps to construct 3D layer-by-layer scaffolds. CONCLUSIONS: We introduced a method to produce layered 3D scaffolds to mimic the cell guiding cues in CNS by alternating the soft hydrogel matrix and fibrous guidance cues. The produced scaffold successfully enabled the long-term culture of hPSC-derived neuronal cells. This layered 3D scaffold is a useful model for in vitro and in vivo neuronal TE applications.publishedVersionPeer reviewe