Bioactive photocrosslinkable resin solely based on refined decellularized small intestine submucosa for vat photopolymerization of in vitro tissue mimics

Elomaa, Laura; Gerbeth, Lorenz; Almalla, Ahed; Fribiczer, Nora; Daneshgar, Assal; Tang, Peter; Hillebrandt, Karl H.; Seiffert, Sebastian; Sauer, Igor M.; Siegmund, Britta; Weinhart, Marie

doi:10.1016/j.addma.2023.103439

Cited by 5 publications

(28 citation statements)

References 53 publications

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“…The preservation of dECM-related growth factors and cytokines after pepsin digestion and chemical modifications has been reported for many tissue types. 56 − 60 In this study, most growth factors are preserved in higher quantities for papain than pepsin digests and located in the same order of magnitude as detected in the originating native ECM. Notably for α-amylase digests, a clear increase in growth factor preservation compared to papain and pepsin digests and occasionally even an enrichment compared to native ECM was observed ( Table S2 ).…”

Section: Discussionmentioning

confidence: 58%

Papain-Based Solubilization of Decellularized Extracellular Matrix for the Preparation of Bioactive, Thermosensitive Pregels

Almalla,

Elomaa,

Bechtella

et al. 2023

Biomacromolecules

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Solubilized, gel-forming decellularized extracellular matrix (dECM) is used in a wide range of basic and translational research and due to its inherent bioactivity can promote structural and functional tissue remodeling. The animal-derived protease pepsin has become the standard proteolytic enzyme for the solubilization of almost all types of collagen-based dECM. In this study, pepsin was compared with papain, α-amylase, and collagenase for their potential to solubilize porcine liver dECM. Maximum preservation of bioactive components and native dECM properties was used as a decisive criterion for further application of the enzymes, with emphasis on minimal destruction of the protein structure and maintained capacity for physical thermogelation at neutral pH. The solubilized dECM digests, and/or their physically gelled hydrogels were characterized for their rheological properties, gelation kinetics, GAG content, proteomic composition, and growth factor profile. This study highlights papain as a plant-derived enzyme that can serve as a cost-effective alternative to animal-derived pepsin for the efficient solubilization of dECM. The resulting homogeneous papain-digested dECM preserved its thermally triggered gelation properties similar to pepsin digests, and the corresponding dECM hydrogels demonstrated their enhanced bioadhesiveness in single-cell force spectroscopy experiments with fibroblasts. The viability and proliferation of human HepaRG cells on dECM gels were similar to those on pure rat tail collagen type I gels. Papain is not only highly effective and economically attractive for dECM solubilization but also particularly interesting when digesting human-tissue-derived dECM for regenerative applications, where animal-derived materials are to be avoided.

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Section: Discussionmentioning

confidence: 58%

Papain-Based Solubilization of Decellularized Extracellular Matrix for the Preparation of Bioactive, Thermosensitive Pregels

Almalla,

Elomaa,

Bechtella

et al. 2023

Biomacromolecules

Self Cite

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“…Additionally, the material waste is often minimized, as in a typical bottom-up vat photopolymerization printer, all the resin can be used until the last drop. However, unlike extrusion printing, which relies on the thermosensitive gelation of a dECM hydrogel, vat photopolymerization requires either free-radical-initiated photocrosslinking of double bond-containing, functionalized dECM [ 32 , 39 , [55] , [56] , [57] ] or ruthenium-initiated photocrosslinking of unfunctionalized dECM [58] . Therefore, additional chemical modification of the dECM and/or use of photoinitiating compounds is necessary for the covalent crosslinking of the hydrogels.…”

Section: Bioprinting Techniques and Gelation Methods Of Solubilized T...mentioning

confidence: 99%

“…In the photopolymerization process, the photoinitiator, when used, absorbs light in either the UV or visible light range, becoming excited into a high-energy radical state. These radicals then react with the functionalized dECM polymers, initiating the crosslinking [32] . In the case of ruthenium chemistry, the tyrosine side groups of dECM are oxidized and converted into radicals, which are quenched through the formation of intermolecular covalent dityrosine bonds [58] .…”

Section: Bioprinting Techniques and Gelation Methods Of Solubilized T...mentioning

confidence: 99%

“…After solubilizing the dECM, it can be directly used for extrusion bioprinting, where gelation occurs through the physical process of fibrillogenesis at physical conditions (37 °C and pH 7.4). However, when the material is intended for use as a photocrosslinkable bioresin, the dECM polymers are typically chemically functionalized with double bond-containing moieties [32] , [33] , [34] . This modification allows for the covalent crosslinking of the dECM using light, enhancing the strength of the resulting hydrogels and improving their handling.…”

Section: Preparing Tissue-derived Decm For Use In Bioinks and Bioresinsmentioning

confidence: 99%

“…As additions to these extrudable bioinks, we have synthesized dECM methacrylamide for multi-layer vat photopolymerization. This was achieved by sequential adding of MAAH to rat liver dECM (31 wt-% of MAAH to dECM, pH 9.7 at RT for 1 d, DOF 98%) [39] and porcine small intestine (103 wt-% of MAAH to dECM, pH 9 at RT for 3 h, DOF 88%), [32] resulting in biomaterial resins suitable for the vat photopolymerization.…”

Section: Preparing Tissue-derived Decm For Use In Bioinks and Bioresinsmentioning

confidence: 99%

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Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins

Elomaa,

Almalla,

Keshi

et al. 2023

Biomaterials and Biosystems

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Photo‐Responsive Decellularized Small Intestine Submucosa Hydrogels

Duong,

Nguyen,

Luong

et al. 2024

Adv Funct Materials

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Decellularized small intestine submucosa (dSIS) is a promising biomaterial for promoting tissue regeneration. Isolated from the submucosal layer of animal jejunum, SIS is rich in extracellular matrix (ECM) proteins, including collagen, laminin, and fibronectin. Following mild decellularization, dSIS becomes an acellular matrix that supports cell adhesion, proliferation, and differentiation. Conventional dSIS matrix is usually obtained by thermal crosslinking, which yields a soft scaffold with low stability. To address these challenges, dSIS is modified with methacrylate groups for photocrosslinking into stable hydrogels. However, dSIS has not been modified with clickable handles for orthogonal crosslinking. Here, the development of norbornene‐modified dSIS, named dSIS‐NB, via reacting amine groups of dSIS with carbic anhydride in acidic aqueous reaction conditions is reported. Using triethylamine (TEA) as a mild base catalyst, high degrees of NB substitution on dSIS are obtained. In addition to describing the synthesis of dSIS‐NB, its adaptability in orthogonal hydrogel crosslinking for cancer and vascular tissue engineering is explored. Impressively, compared with physically crosslinked dSIS and collagen matrices, orthogonally crosslinked dSIS‐NB hydrogels supported rapid dissemination of cancer cells and superior vasculogenic and angiogenic properties. dSIS‐NB is also exploited as a versatile bioink for 3D bioprinting.

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Bioactive photocrosslinkable resin solely based on refined decellularized small intestine submucosa for vat photopolymerization of in vitro tissue mimics

Cited by 5 publications

References 53 publications

Papain-Based Solubilization of Decellularized Extracellular Matrix for the Preparation of Bioactive, Thermosensitive Pregels

Papain-Based Solubilization of Decellularized Extracellular Matrix for the Preparation of Bioactive, Thermosensitive Pregels

Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins

Photo‐Responsive Decellularized Small Intestine Submucosa Hydrogels

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