Mechanobiology in Tissue Engineering

Physical cues are powerful regulators of cell fate. While mechanical loading and magnetic fields have each shown promise independently, their combined magnetomechanical effect on osteochondral regeneration has remained largely unexplored—partly due to the lack of standardized and comparable in vitro platforms. In our latest work published in Biomaterials, we developed a versatile, high-throughput magnetomechanical stimulation system capable of delivering precisely controlled oscillating magnetic fields and cyclic mechanical deformation to 3D constructs in vitro. By pairing this platform with magnetoactive 3D-printed scaffolds containing different magnetic contents, we show that magnetomechanical stimulation alone—without biochemical differentiation cues—can direct cell commitment. Low magnetic content scaffolds favor osteogenic differentiation, with strong upregulation of ALP and osteocalcin, whereas higher magnetic content scaffolds promote chondrogenic commitment, with increased collagen II and aggrecan expression https://lnkd.in/e8RKiDdw Thanks Maria Kalogeropoulou for leading the work #collaboration Pierpaolo Fucile Sophia Dalfino Gianluca Tartaglia Izabela-Cristina Stancu #Biomaterials #TissueEngineering #Magnetomechanics #OsteochondralRegeneration #3Dprinting #Mechanobiology #RegenerativeMedicine

New paper out today in Advanced Healthcare Materials: We pit Myokines vs. Mechanics to establish the separate mechanical & biochemical mechanisms by which muscle contraction programs motor neuron growth and maturation from the bottom up! https://lnkd.in/eaUuZZZb Summary of our findings: Myokines secreted by contracting muscle play important roles throughout the body (highlighting the systemic beneficial impacts of exercise!), but it is difficult to isolate the muscle-specific origin and functional impact of circulating biochemicals in vivo. To dive deeper into bottom-up communication from muscles to motor neurons, we needed a way to efficiently generate large volumes of myokines in vitro i.e. collect conditioned media from contractile muscle monolayers! But contractile 2D muscle monolayers readily delaminate from substrates making it difficult to efficiently collect conditioned media rich in myokines... so we had to develop a fibrin hydrogel formulation that enabled stable culture of highly contractile 2D muscle over several weeks. Leveraging our "myokine factory", we observed that motor neurons grew faster and farther when stimulated with muscle-secreted factors, and that the degree of observed axonogenesis was dependent on muscle contraction intensity (i.e. dose dependent)! But evidence in the literature also points to ways in which the large *mechanical* forces generated during muscle contraction have an impact on neighboring tissues, making us curious to investigate the role of mechanobiology in muscle-motor neuron crosstalk. Leveraging our lab's Magnetic Matrix Actuation (MagMA) platform, we found that dynamic mechanical stimulation of motor neurons (mimicking forces generated during muscle contraction) significantly increased axonogenesis, having an *equivalent* impact to myokine stimulation! Despite morphological similarities, we noted that biochemical stimulation (with myokines) & mechanical stimulation (with MagMA) had different impacts on motor neuron gene expression, with myokines more significantly upregulating genes that play key roles in nerve/synapse maturation. Overall, our experiments highlight the importance of studying bottom-up signaling from muscles to motor neurons, as well as the significance of considering both biochemical *and* mechanical signaling when studying crosstalk with force-generating tissues. This paper builds on our previous in vivo study published in Biomaterials, which showed that targeted stimulation of denervated muscle grafts quickly restored mobility after trauma in mice (indicating regrowth of injured motor neurons). More details in the paper! Kudos to lead author Angel Bu and everyone on the team MIT Department of Mechanical Engineering (MechE) for years of careful experiments and beautiful images!

Happy to share our latest work—a fun interdisciplinary collaboration between Kim Jensen’s team at the Novo Nordisk Foundation Center for Stem Cell Medicine – reNEW and Roche’s Institute of Human Biology. We investigated how tissue architecture instructs development, specifically whether it can transition lab-grown intestinal epithelium from an immature (fetal) state toward a more adult and functional state. Building on earlier work from the lab on geometric organoid patterning (Nikolce Gjorevski et al., https://lnkd.in/gggBM4A4), we extended this technology to probe the intestinal “fetal-to-adult” transition and the role of crypt formation. Shared first authors Martti Maimets (reNEW) and Mike Nikolaev (IHB) combined their complementary expertise in developmental biology and bioengineering to tackle this challenge. Our key findings: * Geometric guidance: We engineered hydrogel scaffolds with native, crypt-mimicking topography. * Tunable crypt geometry: By controlling crypt shape, we modulated cell crowding, which in turn influences maturation, differentiation, and spatial patterning via YAP1 signaling. * Mechanistic biology: Geometry provides a direct way to probe mechanotransduction during maturation, allowing us to separate architectural effects from other complex extrinsic cues present in vivo. Overall, this platform offers a more deterministic way to develop and mature tissues in vitro, with significant potential for creating predictive models in drug safety/efficacy and disease biology studies. A huge thank you to all our fantastic collaborators at reNEW and the contributors at the Institute of Human Biology! Read the full study here: https://lnkd.in/eZVRvE3n #HumanModelSystems #StemCells #Organoids #Bioengineering #CellStemCell #DrugDiscovery #PharmaInnovation

#FluorescenceFriday This week’s image features #iPSC_derived neural progenitor cells (NPCs) encapsulated in our #biomimetic engineered hydrogels at the #Heilshorn_Biomaterials_Group, designed to replicate the biochemical and biomechanical cues of native brain tissue. 🧠 By integrating these advanced hydrogels into our in vitro #neural models, we aim to create platforms that better reflect human #neurobiology, providing a more predictive, human-relevant alternative to animal models for #drug discovery and #personalized medicine. Fluorescent markers used: 🟢/🟣 Tubulin β3 (neuronal cytoskeleton) 🔵/🟡 DAPI (nuclei) 🎥 The GIF video shows 3D #neural_networks forming within the hydrogel at different Z-planes, beautifully illustrating how these cells differentiate and connect throughout the matrix. These hydrogels are more than scaffolds; they’re #programmable #microenvironments that allow us to study how mechanical forces and biochemical cues drive neural development and disease progression. Michelle Huang #NeuralProgenitorCells #iPSCs #BiomimeticHydrogels #BrainTissueEngineering #3DCellCulture #Neuroengineering #FluorescenceImaging #TubulinB3 #DAPI #Biointerfaces #HumanCellModels #RegenerativeMedicine #Mechanobiology #Immunofluorescence #InVitroModels #TissueEngineering #AdvancedMicroscopy #BrainOnChip #PersonalizedMedicine #HighThroughputScreening #NeuroscienceResearch

Researchers built a hydraulically controlled curvature-chip to study how corneal stromal cells respond to disease-level curvature. The platform generates precise curvatures and isolates the mechanobiological effects of geometry on stromal cells. They coated the chip surface using plasma, polydopamine, and collagen, then seeded keratocytes, fibroblasts, or myofibroblasts on top. Curvature alone drove major changes: keratocytes shifted toward a fibrotic phenotype, fibroblasts formed orthogonal alignment similar to native lamellae, and myofibroblasts showed enhanced contractility and ECM remodeling. If you want to make models like this more physiologically relevant, let’s chat about using CollPlant’s recombinant human collagen for coatings. Read the full publication here: https://lnkd.in/g3gxP-w6 #collagen #tissueengineering #cellculture