Biology subjects

Falandt, M.

Publications and source records attributed to Falandt, M..

3 recordsLinked to original sources

bioRxiv2026

A Versatile, Biocompatible Additive for Spatiotemporal Volumetric Photografting of Biochemical and Mechanical Cues in Diverse Hydrogel Matrices

Engineering functional tissue constructs requires not only replicating their 3D architecture but also capturing their dynamic biochemical and mechanical environments. While 3D bioprinting technologies enable spatial control over cell and biomaterial deposition, post-fabrication modulation of material properties remains limited. Photografting approaches allow for spatiotemporal functionalization of certain 3D matrices by chemically binding bioactive factors onto spatially determined regions of a material, but current methods often rely on specialized chemistries with narrow material compatibility. Here, we introduce AddGraft, a biocompatible, off-the-shelf additive designed for semi-orthogonal thiol-ene photografting in vinyl-functionalized hydrogels. AddGraft, a heterobifunctional polyethylene glycol, carries an acrylate moiety for network incorporation during photocrosslinking and a norbornene group for post-crosslinking functionalization. AddGraft integrates into the polymer network during gel crosslinking without altering bulk mechanics, enabling precise modification at any time post-fabrication. We demonstrate compatibility with multiple acrylated biomaterial platforms and light-based volumetric photopatterning technology. Photopatterning achieves high spatial resolution and gradient formation in 3D, while grafting of multi-thiolated crosslinkers allows localized stiffening of hydrogels. Encapsulated human mesenchymal stromal cells exhibit high viability and undergo morphological changes in response to the dynamic tuning of their microenvironment. By decoupling structural and functional roles, AddGraft enables on-demand spatial and temporal control over hydrogel properties. This approach expands the biofabrication toolkit for engineering cell-instructive, 4D tissue environments with translational relevance in regenerative medicine.

bioengineering↗

bioRxiv2025

Hybrid supramolecular-covalent bioresin promotes cell migration and self-assembly in light-based volumetric bioprinted constructs

There is an increasing need for novel biomaterials compatible with advanced biofabrication technologies, which also permit cells to remodel their microenvironment. This remodelling is crucial for maturing tissue constructs into fully functional tissue replacements. Recent progress in supramolecular chemistries has allowed for the production of dynamic biomaterials. Their properties enable bonds to be reversibly broken by cells, facilitating processes requiring morphological changes or migration, crucial for tissue development and homeostasis. Here, we present a one-of-its-kind gelatin-based hybrid covalent/supramolecular biomaterial. We demonstrate the advantage of adding supramolecular-reactive moieties on covalent materials, over covalent bonds alone, in facilitating processes such as cell growth, migration, spreading and organoid proliferation. This is exemplified by enhanced MSC and T cell migration and improved vascular network formation in hybrid hydrogels over covalent-only materials. The combination of supramolecular and covalent bonds further enabled control over photocrosslinking, allowing the use of the material in volumetric bioprinting of complex structures with high shape fidelity. As a proof-of-concept we bioprinted complex breast-like structures from encapsulated normal breast cell lines with a tumor organoid core. We demonstrated that engineered T cells can migrate large distances into the breast tissue, specifically targeting tumor cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/631505v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1e15084org.highwire.dtl.DTLVardef@16d1554org.highwire.dtl.DTLVardef@937d1aorg.highwire.dtl.DTLVardef@fa51f4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Basement membrane hydrogels dampen CAR-T cell activation: nanofibrillar cellulose gels as alternative to preserve T cell function in 3D cell cultures.

BackgroundHydrogel-based 3D culture systems are emerging as a valuable tool for preclinical screening of cell-based immunotherapies against solid and hematological malignancies, such as chimeric antigen receptor T (CAR-T) cells. Hydrogels can influence T cell function in a non-desired manner due to their mechanical properties and chemical composition, potentially skewing results in preclinical testing of novel immunotherapeutic compounds. MethodsIn this study, we assess CD4+ T and CAR-T cell activation and proliferation in chemically-undefined matrices (Matrigel and basement membrane extract, BME) and compare them to a synthetic nanofibrillar cellulose (NFC) hydrogel. ResultsRheometric analyses show that NFC is more rigid than Matrigel and BME. Murine CD4+ T cells acquire a regulatory T cell (Treg) phenotype in Matrigel and BME, while this is not observed in NFC. Proliferation and activation of human T cells are higher in NFC than in Matrigel or BME. Similarly, we show that CAR-T cell activation and proliferation is significantly impaired in Matrigel and BME, in contrast to NFC. ConclusionsOur findings highlight the impact of hydrogel choice on (CAR-)T cell behavior, with direct implications for preclinical immunotherapy testing. In contrast to Matrigel and BME, NFC offers a chemically-defined 3D environment where T cell function is preserved. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSIn 3D (preclinical) tumor-killing assays for evaluating engineered T cell cytotoxicity, the surrounding matrix can influence immune cell phenotype and function, potentially skewing T cell activity. Basement membrane hydrogels such as Matrigel and basement membrane extract (BME), widely used as scaffolds for 3D culture, are inherently heterogeneous and contain extracellular matrix components that can influence lymphocyte function. What this study addsHere, we show that (CAR-)T cell function is significantly reduced in Matrigel and BME as compared to standard (2D) culture conditions. In contrast, (CAR-)T cell activity is preserved in synthetic nanofibrillar cellulose (NFC) gels. Importantly, murine T cells spontaneously acquire a Treg phenotype in Matrigel and BME. T cell proliferation and cytokine secretion are >10-fold lower in Matrigel than in NFC. Similarly, CAR-T cell survival and expansion are 10-fold higher in NFC than in Matrigel or BME. How this study might affect research, practice or policyWe report that the intrinsic cytotoxic and proliferative potential of (CAR-)T cells can be underestimated when performing assays in 3D cultures based on Matrigel or BME. As an alternative, we suggest the use of chemically defined synthetic gels, and we show that nanofibrillar cellulose hydrogels are suitable 3D matrices for preserving T cell phenotype and activation.

immunology↗