Alice Zoso

Gerardina Ruocco

Irene Carmagnola

Mattia Spedicati

Valeria Chiono

English

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18 October 2022POLITECNICO DI TORINORepository ISTITUZIONALETissue-engineered models of human pathological cardiac tissue through bioartificial scaffolds / Carmagnola, Irene; Zoso,Alice; Spedicati, Mattia; Ruocco, Gerardina; Chiono, Valeria. - ELETTRONICO. - (2020). ((Intervento presentato alconvegno 11TH World Biomaterials Congress tenutosi a virtuale nel 11 - 15 December 2020.OriginalTissue-engineered models of human pathological cardiac tissue through bioartificial scaffoldsPublisher:PublishedDOI:Terms of use:openAccessPublisher copyright(Article begins on next page)This article is made available under terms and conditions as specified in the  corresponding bibliographic description inthe repositoryAvailability:This version is available at: 11583/2871550 since: 2021-02-16T17:01:46ZMCI GroupFree SessionTissue and organ modelsWBC2020-3192TISSUE-ENGINEERED MODELS OF HUMAN PATHOLOGICAL CARDIAC TISSUE THROUGH BIOARTIFICIALSCAFFOLDSIrene Carmagnola1, Alice  Zoso1, Mattia Spedicati1, Gerardina Ruocco1, Valeria Chiono* 11Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, ItalyPlease select your preferred method of presentation: Special Symposium - Oral ONLYSymposium: Engineered Microenvironments in DiseaseIntroduction: Myocardial infarction (MI) causes the loss of billions of cardiomyocytes, followed by a pathological process,which leads to myocardial fibrosis and stiffening, and possible cardiac function impairment [1]. Although fully recovery ofhuman heart functionality is currently not possible, many strategies are under investigation with the aim to regeneratemyocardial tissue [2].In  vitro  models  of  human  pathological  cardiac  tissue  able  to  reproduce  post-infarct  microenvironment  are  highlydemanded,  as  predictive  tools  to  screen  new  regenerative  therapies  [3].  However,  human  cardiac  fibrotic  tissue  ischaracterised by a high variability of composition and mechanical properties, depending on infarct size, its location in theventricle, time from heart attack and specific zone in the same infarcted area.In  this  work,  2D  and  3D  “bioartificial”  scaffolds  were  produced  based  on  polycaprolactone  (PCL),  a  well-knownbiocompatible  synthetic  polymer,  surface  grafted  with  gelatin  (G),  a  cell-adhesive  protein.  The  effect  of  scaffoldarchitecture on the composition and structure of the engineered human cardiac fibrotic tissues was evaluated.Experimental methods: 2D and 3D polycaprolactone (PCL) scaffolds were prepared by electrospinning (LinariEngineering) and melt-extruded additive manufacturing (Rokit Invivo), respectively. Gelatin (G) was grafted on thescaffold surface by a two-step method based on: (i) 3,4-Dihydroxy-D,L-phenylalanine (DOPA) polymerisation (PCL-polyDOPA) and (ii) incubation in G solution (PCL-polyDOPA-G). Control PCL-G scaffolds were also prepared. After eachfunctionalization step, physicochemical (ATR-FTIR, XPS, QCM-D), morphological (SEM and profilometry) andmechanical (tensile stress-strain tests, nanoindentation) characterizations were performed. Cardiac fibroblasts isolatedfrom human ventricle (HCFs, PromoCell) were cultured on the scaffolds for up to 3 weeks at a density of 7x104 cells/cm2:their adhesion, proliferation and cardiac protein expression were analysed by immunofluorescence and Western Blotanalysis, compared to 2D cultures.Image:Results and discussions: Electrospun 2D PCL scaffolds were obtained with both a random and an aligned fibremorphology. Square- or rectangular-meshed 3D scaffolds with interconnected pores were produced by melt-extrusionadditive manufacturing (Figure 1).  Successful  surface  modification  of  PCL-polyDOPA-G  scaffolds  was  demonstrated.  Morphology  of  PCL-polyDOPA-Gscaffolds  did  not  significantly  change  compared  to  PCL scaffolds,  while  their  surface  roughness  was  slightly  increased.HCFs  cultured  on  PCL-polyDOPA-G  scaffolds  showed  improved  attachment  and  proliferation  compared  to  non-functionalized PCL scaffolds. The expression of fibrotic markers (α-SMA) and the secretion of typical cardiac extracellularmatrix proteins (Fibronectin, Laminin, Tenascin and Collagen IV) were confirmed. Scaffold geometry affected the type ofdeposited proteins and their distribution and orientation.Conclusions: In this work, 2D and 3D bioartificial PCL-polyDOPA-G scaffolds supported long-term HCF culture, whiletheir structure affected HCF adhesion, fibrotic marker expression and cardiac protein deposition. A comparison of thecomposition and mechanical properties of the engineered constructs with human infarcted samples will allow to define aplatform of PCL-polyDOPA-G scaffolds for the modelling of different degrees of cardiac fibrosis. Results of this studycould be beneficial for the treatment of cardiac fibrosis associated with other pathologies than ischaemic cardiomyopathy,including inherited cardiomyopathy mutations, metabolic syndrome, diabetes, and ageing.References/Acknowledgements: This project has received funding from the European Research Council (ERC) underthe European Union's Horizon 2020 research and innovation programme grant agreement No 772168.[1] A. González et al. Journal of the American College of Cardiology 2018; 71.[2] C. Paoletti et al. Cells 2018;7: 114.[3] J. Veldhuizen et al. J Biol Eng. 2019; 13: 29.Disclosure of Interest: None DeclaredKeywords:  3D scaffolds for TE applications,  Artificial extracellular matrix, In vitro tissue models

Tissue-engineered models of human pathological cardiac tissue through bioartificial scaffolds

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Tissue-engineered models of human pathological cardiac tissue through bioartificial scaffolds

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