More Like this

1. Accurate flow in augmented networks (AFAN): an approach to generating three-dimensional biomimetic microfluidic networks with controlled flow

   https://doi.org/10.1039/C8AY01798K  

   Guo, Jiaming ; Keller, Keely A. ; Govyadinov, Pavel ; Ruchhoeft, Paul ; Slater, John H. ; Mayerich, David ( January 2019 , Analytical Methods)

   In vivo , microvasculature provides oxygen, nutrients, and soluble factors necessary for cell survival and function. The highly tortuous, densely-packed, and interconnected three-dimensional (3D) architecture of microvasculature ensures that cells receive these crucial components. The ability to duplicate microvascular architecture in tissue-engineered models could provide a means to generate large-volume constructs as well as advanced microphysiological systems. Similarly, the ability to induce realistic flow in engineered microvasculature is crucial to recapitulating in vivo -like flow and transport. Advanced biofabrication techniques are capable of generating 3D, biomimetic microfluidic networks in hydrogels, however, these models can exhibit systemic aberrations in flow due to incorrect boundary conditions. To overcome this problem, we developed an automated method for generating synthetic augmented channels that induce the desired flow properties within three-dimensional microfluidic networks. These augmented inlets and outlets enforce the appropriate boundary conditions for achieving specified flow properties and create a three-dimensional output useful for image-guided fabrication techniques to create biomimetic microvascular networks.
2. Layered supramolecular hydrogels from thioglycosides

   https://doi.org/10.1039/d2tb00037g  

   Wang, Yu-Cheng ; Kegel, Laurel L. ; Knoff, David S. ; Deodhar, Bhushan S. ; Astashkin, Andrei V. ; Kim, Minkyu ; Pemberton, Jeanne E. ( April 2022 , Journal of Materials Chemistry B)

   Low molecular weight hydrogels are made of small molecules that aggregate via noncovalent interactions. Here, comprehensive characterization of the physical and chemical properties of hydrogels made from thioglycolipids of the disaccharides lactose and cellobiose with simple alkyl chains is reported. While thiolactoside hydrogels are robust, thiocellobioside gels are metastable, precipitating over time into fibrous crystals that can be entangled to create pseudo-hydrogels. Rheology confirms the viscoelastic solid nature of these hydrogels with storage moduli ranging from 10–600 kPa. Additionally, thiolactoside hydrogels are thixotropic which is a desirable property for many potential applications. Freeze-fracture electron microscopy of xerogels shows layers of stacked sheets that are entangled into networks. These structures are unique compared to the fibers or ribbons typically reported for hydrogels. Differential scanning calorimetry provides gel-to-liquid phase transition temperatures ranging from 30 to 80 °C. Prodan fluorescence spectroscopy allows assignment of phase transitions in the gels and other lyotropic phases of high concentration samples. Phase diagrams are estimated for all hydrogels at 1–10 wt% from 5 to ≥ 80 °C. These hydrogels represent a series of interesting materials with unique properties that make them attractive for numerous potential applications.
3. Scaffold Architecture and Matrix Strain Modulate Mesenchymal Cell and Microvascular Growth and Development in a Time Dependent Manner

   Chiou, Gennifer ; Jui, Elysa ; Rhea, Allison C ; Gorthi, Aparna ; Miar, Solaleh ; Acosta, Francisca M ; Perez, Cynthia ; Suhail, Yasir ; Kz, Kshitiz ; Chen, Yidong ; et al ( August 2020 , Cellular and molecular bioengineering)

   Background Volumetric tissue-engineered constructs are limited in development due to the dependence on well-formed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis. Methods The interaction between mesenchymal stem cells (MSCs) seeded on hydroxyapatite scaffolds of 450, 340, and 250 μm pores and microvascular fragments (MVFs) seeded within 20 mg/mL fibrin hydrogels that were cast into the cell-seeded scaffolds, was assessed in vitro over 21 days and compared to the fibrin hydrogels without scaffold but containing both MSCs and MVFs. mRNA sequencing was performed across all groups and a computational mechanics model was developed to validate architecture effects on predicting vascularization driven by stiffer matrix behavior at scaffold surfaces compared to the pore interior. Results Lectin staining of decalcified scaffolds showed continued vessel growth, branching and network formation at 14 days. The fibrin gel provides no resistance to spread-out capillary networks formation, with greater vessel loops within the 450 μm pores and vessels bridging across 250 μm pores. Vessel growth in the scaffolds was observed to be stimulated by hypoxia and successive angiogenic signaling. Fibrin gels showed linearmore »fold increase in VEGF expression and no change in BMP2. Within scaffolds, there was multiple fold increase in VEGF between days 7 and 14 and early multiple fold increases in BMP2 between days 3 and 7, relative to fibrin. There was evidence of yap/taz based hippo signaling and mechanotransduction in the scaffold groups. The vessel growth models determined by computational modeling matched the trends observed experimentally. Conclusion The differing nature of hypoxia signaling between scaffold systems and mechano-transduction sensing matrix mechanics were primarily responsible for differences in osteogenic cell and microvessel growth. The computational model implicated scaffold architecture in dictating branching morphology and strain in the hydrogel within pores in dictating vessel lengths.« less
4. A multiscale coarse-grained model to predict the molecular architecture and drug transport properties of modified chitosan hydrogels

   https://doi.org/10.1039/d0sm01243b  

   Singhal, Ankush ; Schneible, John D. ; Lilova, Radina L. ; Hall, Carol K. ; Menegatti, Stefano ; Grafmüller, Andrea ( December 2020 , Soft Matter)

   Hydrogels constructed with functionalized polysaccharides are of interest in a multitude of applications, chiefly the design of therapeutic and regenerative formulations. Tailoring the chemical modification of polysaccharide-based hydrogels to achieve specific drug release properties involves the optimization of many tunable parameters, including (i) the type, degree ( χ ), and pattern of the functional groups, (ii) the water–polymer ratio, and (iii) the drug payload. To guide the design of modified polysaccharide hydrogels for drug release, we have developed a computational toolbox that predicts the structure and physicochemical properties of acylated chitosan chains, and their impact on the transport of drug molecules. Herein, we present a multiscale coarse-grained model to investigate the structure of networks of chitosan chains modified with acetyl, butanoyl, or heptanoyl moieties, as well as the diffusion of drugs doxorubicin (Dox) and gemcitabine (Gem) through the resulting networks. The model predicts the formation of different network structures, in particular the hydrophobically-driven transition from a uniform to a cluster/channel morphology and the formation of fibers of chitin chains. The model also describes the impact of structural and physicochemical properties on drug transport, which was confirmed experimentally by measuring Dox and Gem diffusion through an ensemble of modified chitosan hydrogels.
5. Printable homocomposite hydrogels with synergistically reinforced molecular-colloidal networks

   https://doi.org/10.1038/s41467-021-23098-9  

   Williams, Austin H. ; Roh, Sangchul ; Jacob, Alan R. ; Stoyanov, Simeon D. ; Hsiao, Lilian ; Velev, Orlin D. ( May 2021 , Nature Communications)

   The design of hydrogels where multiple interpenetrating networks enable enhanced mechanical properties can broaden their field of application in biomedical materials, 3D printing, and soft robotics. We report a class of self-reinforced homocomposite hydrogels (HHGs) comprised of interpenetrating networks of multiscale hierarchy. A molecular alginate gel is reinforced by a colloidal network of hierarchically branched alginate soft dendritic colloids (SDCs). The reinforcement of the molecular gel with the nanofibrillar SDC network of the same biopolymer results in a remarkable increase of the HHG’s mechanical properties. The viscoelastic HHGs show >3× larger storage modulus and >4× larger Young’s modulus than either constitutive network at the same concentration. Such synergistically enforced colloidal-molecular HHGs open up numerous opportunities for formulation of biocompatible gels with robust structure-property relationships. Balance of the ratio of their precursors facilitates precise control of the yield stress and rate of self-reinforcement, enabling efficient extrusion 3D printing of HHGs.