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1. Engineering a macroporous fibrin-based sequential interpenetrating polymer network for dermal tissue engineering

   https://doi.org/10.1039/D0BM01161D  

   Gsib, Olfat; Eggermont, Loek J.; Egles, Christophe; Bencherif, Sidi A. (December 2020, Biomaterials Science)

   null (Ed.)

   The success of skin tissue engineering for deep wound healing relies predominantly on the design of innovative and effective biomaterials. This study reports the synthesis and characterization of a new type of naturally-derived and macroporous interpenetrating polymer network (IPN) for skin repair. These biomaterials consist of a biologically active fibrous fibrin network polymerized within a mechanically robust and macroporous construct made of polyethylene glycol and biodegradable serum albumin (PEGDM- co -SAM). First, mesoporous PEGDM- co -SAM hydrogels were synthesized and subjected to cryotreatment to introduce an interconnected macroporous network. Subsequently, fibrin precursors were incorporated within the cryotreated PEG-based network and then allowed to spontaneously polymerize and form a sequential IPN. Rheological measurements indicated that fibrin-based sequential IPN hydrogels exhibited improved and tunable mechanical properties when compared to fibrin hydrogels alone. In vitro data showed that human dermal fibroblasts adhere, infiltrate and proliferate within the IPN constructs, and were able to secrete endogenous extracellular matrix proteins, namely collagen I and fibronectin. Furthermore, a preclinical study in mice demonstrated that IPNs were stable over 1-month following subcutaneous implantation, induced a minimal host inflammatory response, and displayed a substantial cellular infiltration and tissue remodeling within the constructs. Collectively, these data suggest that macroporous and mechanically reinforced fibrin-based sequential IPN hydrogels are promising three-dimensional platforms for dermal tissue regeneration. 

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2. 3D printing assisted surface patterning process on acrylated hydrogels for contact guidance of fibroblasts

   https://doi.org/10.1016/j.colsurfb.2024.114099  

   Natarajan, Amrita; Kim, Suntae; Moreno, Gerardo Hernandez; Eyckmans, Jeroen; Chen, Christopher S; Dean, Derrick; Vijayan, Vineeth M (October 2024, Colloids and Surfaces B: Biointerfaces)

   Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels. The template was 3-D printed and has the diameter of a well in a 24-well plate. Hyaluronic acid methacrylate (HA) hydrogel precursor solutions were cast on the 3D printed template’s surface, which generated 3D square shape topographies on the HA hydrogel surface upon demolding. The 3D Laser Microscopy has shown the formation of a periodic array of 3D topographies on hydrogel surfaces. 3D Laser and Electron Microscopy Imaging have revealed that this new method has increased the surface area and exposed the underlying pore structure of the HA hydrogels. To demonstrate the method’s versatility, we have successfully applied this technique to generate 3D topography on two more acrylate hydrogel formulations, gelatin Methacrylate and polyethylene glycol dimethacrylate. Human neonatal dermal fibroblast cells were used as a model cell line to evaluate the cell guidance potential of patterned HA hydrogel. Confocal fluorescence microscopy imaging has revealed that the 3D surface topographies on HA hydrogels can guide and align the actin filaments of the fibroblasts presumably due to the contact guidance mechanism. The newly developed methodology of 3D topography generation in acrylate hydrogels may influence the cell responses on hydrogel surfaces which can impact biomedical applications such as tissue engineering, wound healing, and disease modeling. 

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3. The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration

   https://doi.org/10.3390/cells8030242  

   Yan, Yuanwei; Bejoy, Julie; Marzano, Mark; Li, Yan (March 2019, Cells)

   The mechanism that causes the Alzheimer’s disease (AD) pathologies, including amyloid plaque, neurofibrillary tangles, and neuron death, is not well understood due to the lack of robust study models for human brain. Three-dimensional organoid systems based on human pluripotent stem cells (hPSCs) have shown a promising potential to model neurodegenerative diseases, including AD. These systems, in combination with engineering tools, allow in vitro generation of brain-like tissues that recapitulate complex cell-cell and cell-extracellular matrix (ECM) interactions. Brain ECMs play important roles in neural differentiation, proliferation, neuronal network, and AD progression. In this contribution related to brain ECMs, recent advances in modeling AD pathology and progression based on hPSC-derived neural cells, tissues, and brain organoids were reviewed and summarized. In addition, the roles of ECMs in neural differentiation of hPSCs and the influences of heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and hyaluronic acid on the progression of neurodegeneration were discussed. The advantages that use stem cell-based organoids to study neural degeneration and to investigate the effects of ECM development on the disease progression were highlighted. The contents of this article are significant for understanding cell-matrix interactions in stem cell microenvironment for treating neural degeneration. 

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4. Serial Passaging Affects Stromal Cell Mechanosensitivity on Hyaluronic Acid Hydrogels

   https://doi.org/10.1002/mabi.202300110  

   Sumey, Jenna L.; Harrell, Abigail M.; Johnston, Peyton C.; Caliari, Steven R. (January 2024, Macromolecular Bioscience)

   Abstract There is a tremendous interest in developing hydrogels as tunable in vitro cell culture platforms to study cell response to mechanical cues in a controlled manner. However, little is known about how common cell culture techniques, such as serial expansion on tissue culture plastic, affect subsequent cell behavior when cultured on hydrogels. In this work, a methacrylated hyaluronic acid hydrogel platform is leveraged to study stromal cell mechanotransduction. Hydrogels are first formed through thiol‐Michael addition to model normal soft tissue (e.g., lung) stiffness (E ≈ 1 kPa). Secondary cross‐linking via radical photopolymerization of unconsumed methacrylates allows matching of early‐ (E ≈ 6 kPa) and late‐stage fibrotic tissue (E ≈ 50 kPa). Early passage (P1) human bone marrow mesenchymal stromal cells (hMSCs) display increased spreading, myocardin‐related transcription factor‐A (MRTF‐A) nuclear localization, and focal adhesion size with increasing hydrogel stiffness. However, late passage (P5) hMSCs show reduced sensitivity to substrate mechanics with lower MRTF‐A nuclear translocation and smaller focal adhesions on stiffer hydrogels compared to early passage hMSCs. Similar trends are observed in an immortalized human lung fibroblast line. Overall, this work highlights the implications of standard cell culture practices on investigating cell response to mechanical signals using in vitro hydrogel models. 

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5. Tunable Human Myocardium Derived Decellularized Extracellular Matrix for 3D Bioprinting and Cardiac Tissue Engineering

   https://doi.org/10.3390/gels7020070  

   Basara, Gozde; Ozcebe, S. Gulberk; Ellis, Bradley W.; Zorlutuna, Pinar (June 2021, Gels)

   The generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cell derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modeling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over the mechanical properties along with the cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink. 

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