Revista nº 809

Ruiz-de-Almirón Ingeniería tisular del miocardio · 42 · Actualidad Médica · Número 809 · Enero/Abril 2020 Páginas 39 a 47 attachment, growth and migration, mechanical support and a controlled degradation rate with no toxicity or inflammation risk to the cells (10). Naturals polymers shows biological properties that better fit to the regular microenvironment of tissues, promoting desi- rable cellular response, biocompatibility and degradability. They are derived from biological sources and the most common mate- rials in cardiac tissue engineering are collagen and gelatin (deri- ved from mammalian extracellular matrix) and alginate. The use of natural materials has been expanded through incorporation into co-polymer structures with synthetic biomaterials, such as polycapralactone and poly-L-lactic acid, or chitosan for improve- ment of scaffold or hydrogel properties. As for the synthetic po- lymers are an attractive alternative to natural materials because they have the ability to control the entire synthesis procedure, their mechanical properties, topography and structure of the ma- terial. Consequently, they are preferred for in vivo applications to allow for the engineered tissue to integrate and minimize adverse host response. The most notable polyesters are FDA-approved polycapralactone, poly-L-lactic acid, and poly(lactic-co-glycolic acid), which have been applied in many tissue engineering appli- cations (29). It is essential to use biocompatible and biodegrada- bility gels in order to avoid both long-term bioreactions and toxic inflammatory reactions (30). Biomimetic scaffold can be used alone as acellular scaffolds or in combination with cells (31) and generally must be non-inmunogenic, mechanically stable and flexible, allow physiological electrical propagation and nutrients to the cells, and have biodegradability rate. When combined with cells (Ta- ble 2) they may improve the retention of transplanted cells as well as increase cell survival. Injection of acellular scaffolds with or without bioactive molecules aids in structural mecha- nic support, decrease of fibrosis and ventricular dilation, as well as promotes recruitment of native stem cells and angio- genesis (26,32). Recently, McLaughlin et al. have reported the first injectable biomaterials made from recombinant human collagens type I (rHCI) and type III (rHCIII), instead of using animal-derived components. After pre-clinical performance in a well-established mouse model of MI, their results highlight the potential for a biomaterial based on human recombinant collagen to be used as therapy for the improvement of cardiac function post-MI (33). b) Hydrogels Hydrogels are the most commonly used polymers in tissue engineering and exactly they are the natural extracellu- lar matrix protein collagen I, mixtures of collagen I and matrigel and the blood-clotting material fibrin (32,34,35). The elasticity and swelling properties of hydrogels make them desirable for injectable purposes and bioprinting applications. Pororsity and mechanical properties are also important in terms of biocompa- tibility and structural similarity to the native ECM (10). Already in the 90s, Eschenhagen et al . (36) succeeded in obtaining three-dimensional heart tissue developing a method for cultivating cardiomyocytes in a collagen matrix and allowed them to gel between two Velcro-coated glass tubes. This opened up the possibility of being able to study in vitro the functional consequences of genetic or pharmacological manipulation of car- diomyocytes under highly controlled conditions. Some research groups have developed a natural and biodegradable hybrid composed by human fibrin and agarose type VII, a polysaccharide originating from algae (FAH). It has been applicated in the construction of different engineered tissues like cornea (37), skin (38), oral mucosa (24) and pe- ripheral nerve (39) among others, and they have shown that the nanostructuration and cross-linking techniques improved the biomechanical and structural properties of different bio- materials. IN VITRO ENGINEERED TISSUE IN SITU ENGINEERED TISSUE Gelatin → Alone or with fetal cardiomyocytes Alginate → With fetal cardiomyocytes Alginate and matrigel → w/SDF-1, IGF-1 and VEGF w/Neonatal CM + SDF-1, IGF-1 and VEGF Poly(glycolide)/poly(lactide) → With dermal fibroblasts Collagen type I and matrigel → w/SkM PTFE, PLA mesh, collagen type I and matrigel → Alone or w/ hBMC-derived MSCs Collagen type I → Alone or w/BMC, HUCBCs, hBMC CD133+, hMSC, hSkM. PNIPAAM (cell culture dish) → Cell sheet of neonata CM or adipose-derived MCSs Decellularized myocardium/fibrin → w/mesenchymal progenitor cells Pericardium → w/MSCs Fibrin → Alone or w/hESc-derived Ecs and hESC-derived MSCs Fibrin → Alone or with BMCs, ASCs, MCSCs, BMMNCs w/bFGF, HGF, TGFβ-1 Alginate → Alone, PDGF-BB, IGF-1, HGF w/hMSCs or w/Polypyrrole Collagen → Alone or w/BMC Hyaluronic acid → Alone Myocardial and Pericardial matrix → Alone Alginate → Alone or w/VEGF, PDGF-BB, IGF-1, HGF w/hMSCs or w/Polypyrrole Matrigel → Alone or w/ ESC Collagen type I and matrigel → Alone or w/neonatal CM Self-assembling peptides → Alone or w/nenonatal CM, PDGF-BB Gelatin → Alone or w/bFGF Calcium hydroxyapatite → Alone Chitosan → Alone or w/ ESCs, bFGF, neonatal CM w/Polypyrrole Table 2. Main biomaterials researched for treatment of MI. ASC: adipose-derived stem cell; bFGF: basic fibroblast growth factor; BMC: bone marrow cell; BMMNC; bone marrow-derived stem cell; CM: cardiomyocyte; ESC: embryonic stem cells; HGF: hepatocyte growth factor; HUCBC: human umbilical cord blood mononuclear cell; MSC: mesenchymal stem cell; IGF: insulin-like growth factor; PDGF: platelet-derived growth factor; PLA: poly (L-lactic) acid; PNIPAAM: poly (N-isopropylacrylamide); PTFE: poly (tetrafluoroethylene); SDF: stromal cell–derived factor; SkM: skeletal myoblast; TGF: transforming growth factor; VEGF: vascular endothelial growth factor. (Adapted from ref. 31).