Revista nº 809

Ruiz-de-Almirón Ingeniería tisular del miocardio · 45 · Actualidad Médica · Número 809 · Enero/Abril 2020 Páginas 39 a 47 In spite of these advances, it is needed in the future to in- tegrate all conventional 3D tissue engineering techniques (3D scaffold fabrication techniques, hydrogels, nanofibers, and dece- llularization) with modern scaffold-free 3D bioprinting to achieve the most realistic functional heart (50). OUTLOOK AND CONCLUSIONS Tissue engineering is essential for the construction of arti- ficial tissues, disease modeling and drug screening. Its objective was traditionally and it still is to provide in vitro functional tissues by mimicking the native ECM composition and structure. Main current challenges are the inconsistency of the ro- dents hearts studies due to the substantial differences in the car- diac physiology of these with to human heart. Thus, testing has to be performed in animals with a cardiac physiology closer to that of humans and it is necessary improved the TE strategies to in- crease cell retention. (34,53). Actually, the use of tissue-enginee- red constructs for myocardial regeneration is still in the preclinical phase, with some exceptions (reflect on ref. 53). To date, there are several important points. Firstly, cardiac tissue engineering offers teorical advantages over cell therapy such as better cell retention or a controlled environment, and myocardial regeneration must be considered as a global and ba- lanced process involving both cells and other cardiac structures. Electromechanical cellular coupling within the matrix is funda- mental to restore cardiac function and the vascularization of the artificial tissue will determine its own viabilty and integration with the host tissue. The benefits of an acellular injectable bio- materials are being disscused because they suggest promoting angiogenesis in preclinical models and have been demostrated to prevent adverse remodeling after myocardial infarction, but nevertheless some randomized trials with natural biomaterial alginate have failed to provide functional benefits. It is impor- tant to optimize the selection of appropriate biomaterials and processes for further studies in vitro and in vivo focused on how to achieve an adequate in vitro vascularization and perfusion of engineered constructs for generation large tissue construct to replace a scar and to create appropriate models to test safety and efficacy of human heart engineered tissue (25). Secondly, as for the challenges presented by hydrogels, it has been improved theirs physical-chemical properties such as stiffness, porosity, degradability and cell adhesion properties among others, to fabricate complex biomimetic architectures for specific tissue regeneration. Combining these hydrogels with stem cell technologies and optimized physical-chemical cues will further allow for the mimicking of the dynamic rege- neration-stage specific microenvironment (8,42,43). And fina- lly, pure decellularized extracellular matrices (dECM) materials have been shown to improve cardiac functionality in a large animal models post-MI or ischemia, with improved angioge- nesis, reduction in inflammatory response, increased progeni- tor cell recruitment, and stimulation of positive remodeling. So, combined pure dECM materials with cells, additional biomate- rials, or paracrine factors suggest an approach based on combi- national therapies (35,46). In conclusion, the complexity of the biological processes in regeneration are evident and some quentions remain hidden. Although cardiac tissue engineering is not one of the most active areas of research compared to bone tissue engineering or skin tissue engineering, it has been made considerable progresses in this field with satisfactory results in some clinical studies showing many benefits. Hydrogel-based matrices seem like interesting biomaterials for engineered tissue scaffolds due to their simila- rity to native ECM and advanced nanotechnologies have enabled to improve the properties of hydrogels. Also, dECM has received a considerable interest because of it preserves the native tissue composition, and 3D bioprintings human tissues of disease may improve the efficacy of regenerative medicine strategies and en- hance the translation to the clinic of promising approaches. Re- garding the transfer to the clinic, since the development of these tissue engineering products is mainly carried out at universities and public hospitals, the support of non-comercial clinical trials and multidisciplinary groups is essential to facilitate tranferring basic research to the clinic. REFERENCIAS BIBLIOGRÁFICAS 1. Micheu MM. Moving forward on the pathway of cell-based therapies in ischemic heart disease and heart failure - time for new recommendations? World J Stem Cells. 2019 Aug 26;11(8):445-451 2. Madonna R, Van Laake L, Botker H.E et al. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc Res. 2019 Mar 1; Vol. 115, Issue 3, pp. 488–500. 3. Alrefai MT, Murali D, Paul A, Ridwan KM, Connell JM, Shum- Tim D. Cardiac tissue engineering and regeneration using cell- based therapy. 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