Chemistry matters

A side-by-side comparison of two chemically distinct methacryloylated dECM bioresins for vat photopolymerization

authored by: Ahed Almalla, Laura Elomaa, Nora Fribiczer, Timm Landes, Peng Tang, Zeinab Mahfouz, Beate Koksch, Karl Hilbert Hillebrandt, Igor Maximillian Sauer, Dag Heinemann, Sebastian Seiffert, Marie Weinhart
Abstract: Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2–2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5–83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting.
Organisation(s): PhoenixD: Photonics, Optics, and Engineering - Innovation Across Disciplines
Phytophotonics
Abteilung Phytophotonik
Institute of Physical Chemistry and Electrochemistry
External Organisation(s): Freie Universität Berlin (FU Berlin)
Johannes Gutenberg University Mainz
Charité - Universitätsmedizin Berlin
Type: Article
Journal: Biomaterials Advances
Volume: 160
ISSN: 2772-9508
Publication date: 07.04.2024
Publication status: E-pub ahead of print
Peer reviewed: Yes
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering, Biomaterials
Electronic version(s): https://doi.org/10.1016/j.bioadv.2024.213850 (Access: Open)

BibTeX

@article{b00db29baaba48d6a6c88483dceb1074,
title = "Chemistry matters: A side-by-side comparison of two chemically distinct methacryloylated dECM bioresins for vat photopolymerization",
abstract = "Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2–2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5–83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting.",
keywords = "Bioink, Biopolymer resin, Digital light processing, Liver matrix, Methacrylation, Photorheology",
author = "Ahed Almalla and Laura Elomaa and Nora Fribiczer and Timm Landes and Peng Tang and Zeinab Mahfouz and Beate Koksch and Hillebrandt, {Karl Hilbert} and Sauer, {Igor Maximillian} and Dag Heinemann and Sebastian Seiffert and Marie Weinhart",
note = "Financial support is kindly acknowledged from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) for CRC 1449 (Project ID 431232613, M.W., B.K.), the Research Unit FOR 2811 (S.S., M.W.) (Project ID 397384169 and 423791428), and the Cluster of Excellence Matters of Activity, Image Space Material (M.W., I.M.S.) under Germany's Excellence Strategy – EXC 2025. A.A. warmly thanks Helmholtz Graduate School Macromolecular Bioscience and Dahlem Research School of Freie Universit{\"a}t Berlin for their support. The authors extend their sincere gratitude for the support provided by the Core Facility BioSupraMol, generously funded by the DFG. Special appreciation is also expressed to Johanna Scholz for her assistance in cell culture. Some icons in the TOC Figure and Fig. 5 were used from flaticon.com or Biorender.com.",
year = "2024",
month = apr,
day = "7",
doi = "10.1016/j.bioadv.2024.213850",
language = "English",
volume = "160",
journal = "Biomaterials Advances",
issn = "2772-9508",
publisher = "Elsevier",
}