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1. Bioactive Polyurethane–Poly(ethylene Glycol) Diacrylate Hydrogels for Applications in Tissue Engineering

   https://doi.org/10.3390/gels10020108  

   Yuan, Yixuan; Tyson, Caleb; Szyniec, Annika; Agro, Samuel; Tavakol, Tara N.; Harmon, Alexander; Lampkins, DessaRae; Pearson, Lauran; Dumas, Jerald E.; Taite, Lakeshia J. (February 2024, Gels)

   Polyurethanes (PUs) are a highly adaptable class of biomaterials that are among some of the most researched materials for various biomedical applications. However, engineered tissue scaffolds composed of PU have not found their way into clinical application, mainly due to the difficulty of balancing the control of material properties with the desired cellular response. A simple method for the synthesis of tunable bioactive poly(ethylene glycol) diacrylate (PEGDA) hydrogels containing photocurable PU is described. These hydrogels may be modified with PEGylated peptides or proteins to impart variable biological functions, and the mechanical properties of the hydrogels can be tuned based on the ratios of PU and PEGDA. Studies with human cells revealed that PU–PEG blended hydrogels support cell adhesion and viability when cell adhesion peptides are crosslinked within the hydrogel matrix. These hydrogels represent a unique and highly tailorable system for synthesizing PU-based synthetic extracellular matrices for tissue engineering applications. 

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2. Rheological Characterization of Alginate Based Hydrogels for Tissue Engineering

   https://doi.org/10.1557/adv.2017.8  

   Duan, Pengfei; Kandemir, Nehir; Wang, Jiajun; Chen, Jinju (January 2017, MRS Advances)

   ABSTRACT Hydrogels have been widely used in many applications from tissue engineering to drug delivery systems. For both tissue engineering and drug delivery, the mechanical properties are important because they would affect cell-materials interactions and injectability of drugs encapsulated in hydrogel carriers. Therefore, it is important to study the mechanical properties of these hydrogels, particularly at physiological temperature (37°C). This study adopted strain sweep and frequency sweep rotational rheological tests to investigate the rheological characteristics of various tissue engineering relevant hydrogels with different concentrations at 37°C. These hydrogels include alginate, RGD-alginate, and copolymerized collagen/alginate/fibrin. It has revealed that the addition of RGD has negligible effect on the elastic modulus and viscosity of alginate. Alginate gels have demonstrated shear thinning behavior which indicates that they are suitable candidates as carriers for cells or drug delivery. The addition of collagen and fibrin would reinforce the mechanical properties of alginate which makes it a strong scaffold material. 

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3. 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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4. Cells utilize strain hardening and crosslinking to establish their extracellular niche in fibrous tissue

   Jagiello, A.; Lim, M.; Botvinick, E. (March 2021, APS March Meeting 2021)

   Bulk measurements of ECM stiffness are commonly used in mechanobiology. However, peri-cellular stiffness can be quite heterogenous and divergent from the bulk properties. Here, we use optical tweezers active microrheology (AMR) to quantify how two different cell lines embedded in 1.0 and 1.5 mg/ml type 1 collagen (T1C) establish dissimilar patterns of peri-cellular stiffness. We found that dermal fibroblasts (DFs) increase local stiffness of 1.0 mg/ml T1C hydrogels, but surprisingly do not alter stiffness of 1.5 mg/ml T1C hydrogels. In contrast, MDA-MB-231 cells (MDAs) predominantly do not stiffen T1C hydrogels, as compared to cell-free controls. Results suggest that MDAs adapt to the bulk ECM stiffness, while DFs regulate local stiffness to levels they intrinsically “prefer”. Further, cells were subjected to treatments, that were previously shown to alter migration, proliferation and contractility of DFs and MDAs. Following treatment, both cell lines established different levels of stiffness magnitude and anisotropy, which were dependent on the cell line, T1C concentration and treatment. In summary, our findings demonstrate that AMR reveals otherwise masked mechanical properties such as spatial gradients and anisotropy, which are known to affect cell behavior at the macro-scale. 

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5. Biocompatible Polyglycidol-based hydrogels for load-bearing tissue engineering

   Beezer, Dain; Harth, Eva (March 2024, SciMeetings, A product from ACS Publications)

   The post-polymerization modification of polyglycidol is of great interest for the synthesis of functional polyether-based polymeric biomaterials. We present a degradable polyglycidol-based hydrogel system using oxime click chemistry by employing a ketone-functionalized and an amino-oxy functionalized branched polyglycidol. Ratio-controlled amino-oxy functionalized species were obtained by controlling the ratio of N-hydroxy phthalimide to the hydroxyl groups attached to the polyether backbone. A similar strategy was utilized to obtain ratio-controlled keto functionalized branched polyglycidols. This unique feature will allow for the tailoring of this branched PEG-like structural motif for the synthesis of novel biomaterials with tailored biochemical and biomechanical properties. The bio-orthogonal nature of this crosslinking reaction makes these hydrogels an attractive option for load-bearing tissue engineering. Our hydrogel synthesis methodology allows for control over the properties of the resulting polymeric network, based upon the ratio between the keto and the amino-oxy functionalities. The potential of these polyether-based networks to serve as a successful delivery platform was assessed by studying their swelling and degradation profiles. Biocompatibility and cytotoxicity of the gels were studied using NIH 3T3 cells. Our preliminary results highlighting the potential of our hydrogels platform will be discussed. 

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