Human Chorionic Membrane-derived Tunable Hydrogels for Vascular Tissue Engineering Strategies

resumo

One of the foremost targets in the advancement of biomaterials to engineer vascularized tissues is not only to replicate the composition of the intended tissue but also to create thicker structures incorporating a vascular network for adequate nutrients and oxygen supply. For the first time, to the best of current knowledge, a clinically relevant biomaterial is developed, demonstrating that hydrogels made from the human decellularized extracellular matrix can exhibit robust mechanical properties (in the kPa range) and angiogenic capabilities simultaneously. These properties enable the culture and organization of human umbilical vein endothelial cells into tubular structures, maintaining their integrity for 14 days in vitro without the need for additional polymers or angiogenesis-related factors. This is achieved by repurposing the placenta chorionic membrane (CM), a medical waste with an exceptional biochemical composition, into a valuable resource for bioengineering purposes. After decellularization, the CM underwent chemical modification with methacryloyl groups, giving rise to methacrylated CM (CMMA). CMMA preserved key proteins, as well as glycosaminoglycans. The resulting hydrogels rapidly photopolymerize and have enhanced strength and customizable mechanical properties. Furthermore, they demonstrate angio-vasculogenic competence in vitro and in vivo, holding significant promise as a humanized platform for the engineering of vascularized tissues.

palavras-chave

DECELLULARIZED EXTRACELLULAR-MATRIX; REGENERATIVE MEDICINE; IN-VITRO; NETWORK FORMATION; STEM-CELLS; HUMAN TERM; COLLAGEN; LAMININ; ECM; MATURATION

categoria

Engineering; Science & Technology - Other Topics; Materials Science

autores

Martins, EAG; Deus, IA; Gomes, MC; Silva, AS; Mano, JF; Custódio, CA

Grupos

G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Bioinspired tile-matching to create ultrastructured bone microtissues in a close-to-native fashion (TETRISSUE)

Human based bioinks to engineer physiologically relevant tissues (HumanINK)

Full human-based multi-scale constructs with jammed regenerative pockets for bone engineering. (REBORN)

Human Platelet Lysates-based Scaffolds for Interfacial Multi-tissue Repair (INTERLYNK)

agradecimentos

Elisa A.G Martins and Ines A. Deus acknowledge the financial support provided by the Portuguese Foundation for Science and Technology (FCT) for the doctoral grants (SFRH/BD/05665/2021) and (SFRH/BD/05271/2021). Ana S. Silva and Catarina A. Custodio also acknowledge the financial support given by the FCT for individual contracts CEECIND/2021.02196 and CEECIND/2020.01647, respectively. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by National Funds through the FCT/MCTES (PIDDAC). This work was also supported by funding from the European Union's Horizon 2020 research and innovation program for project Interlynk [10.3030/953169] and the funding from European Research Council (ERC) for projects Reborn [10.3030/883370 ERC-2019-ADG] and HumanINK [10.3030/101082210 ERC-2022-PoC]. The authors acknowledge the financial support from the project "'TETRISSUE"' (PTDC/BTM-MAT/3201/2020). The TETRISSUE project was acknowledged for the individual Junior Researcher contract of M.C.G. The authors also acknowledge Marta Teixeira Pinto for the CAM assay technique performed at the "in vivo CAM assays" i3S Scientific Platform. The authors would like to thank Catia Monteiro for the confocal image acquisition.