New Publication: Screening of MMP-13 Inhibitors Using a GelMA-Alginate Interpenetrating Network Hydrogel-Based Model Mimicking Cytokine-Induced Key Features of Osteoarthritis In Vitro

We are delighted to announce the publication of our latest research in Polymers, marking a significant milestone for our team. This paper represents the first publication for Alessandra Palladino and a key contribution from Qichan Hu towards her PhD thesis:

Title: Screening of MMP-13 Inhibitors Using a GelMA-Alginate Interpenetrating Network Hydrogel-Based Model Mimicking Cytokine-Induced Key Features of Osteoarthritis In Vitro

Authors: Hu, Q.; Williams, S.L.; Palladino, A.; Ecker, M.

Journal: Polymers 2024, 16, 1572

DOI: https://doi.org/10.3390/polym16111572

Abstract:

Osteoarthritis (OA) is a chronic joint disease characterized by irreversible cartilage degradation. Current clinical treatments lack effective pharmaceutical interventions targeting the root causes of OA. This study explores the use of matrix metalloproteinase (MMP) inhibitors to slow OA progression by addressing cartilage degradation mechanisms.

Our research utilized a GelMA-alginate hydrogel-based 3D in vitro model, which closely mimics the native extracellular matrix (ECM) and the cytokine-induced conditions of OA. This model was used to test MMP-13 inhibitors, as MMP-13 is a major contributor to articular cartilage degradation. The results showed significant inhibition of type II collagen breakdown, demonstrated by measuring C2C concentration using ELISA after treatment with MMP-13 inhibitors. Despite inconsistencies in human cartilage explant samples, our findings highlight the potential of this hydrogel-based model as an alternative to human cartilage explants for in vitro drug screening.

Confirmation of chondrogenesis in GelMA-alginate hydrogel. (a) qRT-PCR analysis of
gene expression of chondrogenic markers. Gene expression is normalized to GAPDH and expressed
relative to the control group (Day 0). Data are presented as mean ± SD with statistical significance
indicated as * p < 0.05 and ** p < 0.01.

Significance:

This research offers a promising platform for preclinical testing of OA treatments, advancing our understanding and development of effective pharmaceutical interventions.

For more information, please read the full paper here.

We are excited to contribute to the field of osteoarthritis research and look forward to future advancements.

Keywords:

Osteoarthritis, MMP-13 Inhibitors, GelMA-Alginate Hydrogel, 3D In Vitro Model, Cytokine-Induced OA Model, Type II Collagen Breakdown, Preclinical Testing.

New Publication: Precision Engineering of Chondrocyte Microenvironments: Investigating the Optimal Reaction Conditions for Type B Gelatin Methacrylate Hydrogel Matrix for TC28a2 CellsNew Publication:

The newest publication from our lab is now available online!

This research was led by Qichan and is co-authored by Marc Anthony.

Abstract

Gelatin methacrylate (GelMA) is a photocrosslinkable biomaterial that has gained widespread use in tissue engineering due to its favorable biological attributes and customizable physical and mechanical traits. While GelMA is compatible with various cell types, distinct cellular responses are observed within GelMA hydrogels. As such, tailoring hydrogels for specific applications has become imperative. Thus, our objective was to develop GelMA hydrogels tailored to enhance cell viability specifically for TC28a2 chondrocytes in a three-dimensional (3D) cell culture setting. We investigated GelMA synthesis using PBS and 0.25M CB buffer, analyzed the mechanical and physical traits of GelMA hydrogels, and evaluated how varying GelMA crosslinking conditions (GelMA concentration, photoinitiator concentration, and UV exposure time) affected the viability of TC28a2 chondrocytes. The results revealed that GelMA synthesis using 0.25M CB buffer led to a greater degree of methacrylation compared to PBS buffer, and the LAP photoinitiator demonstrated superior efficacy for GelMA gelation compared to Irgacure 2959. Additionally, the stiffness, porosity, and swelling degree of GelMA hydrogels were predominantly affected by GelMA concentration, while cell viability was impacted by all crosslinking conditions, decreasing notably with increasing GelMA concentration, photoinitiator concentration, and UV exposure time. This study facilitated the optimization of crosslinking conditions to enhance cell viability within GelMA hydrogels, a critical aspect for diverse biomedical applications.

Do you want to read more? The full publication can be found here:

Q. Hu, M. A. Torres, H. Pan, S. L. Williams and M. Ecker, M. Precision Engineering of Chondrocyte Microenvironments: Investigating the Optimal Reaction Conditions for Type B Gelatin Methacrylate Hydrogel Matrix for TC28a2 Cells. J. Funct. Biomater., 2024, 15.

https://doi.org/10.3390/jfb15030077

New Publication: Multifaceted Shape Memory Polymer Technology for Biomedical Application: Combining Self-Softening and Stretchability Properties

The newest publication from our lab is now online available!

This research was led by Chandani and is co-authored by Marc Anthony and Qichan.

Abstract

Thiol-ene polymers are a promising class of biomaterials with a wide range of potential applications, including organs-on-a-chip, microfluidics, drug delivery, and wound healing. These polymers offer flexibility, softening, and shape memory properties. However, they often lack the inherent stretchability required for wearable or implantable devices. This study investigated the incorporation of di-acrylate chain extenders to improve the stretchability and conformability of those flexible thiol-ene polymers. Thiol-ene/acrylate polymers were synthesized using 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropanetris (3-mercaptopropionate) (TMTMP), and Polyethylene Glycol Diacrylate (PEGDA) with different molecular weights (Mn 250 and Mn 575). Fourier Transform Infrared (FTIR) spectroscopy confirmed the complete reaction among the monomers. Uniaxial tensile testing demonstrated the softening and stretching capability of the polymers. The Young’s Modulus dropped from 1.12 GPa to 260 MPa upon adding 5 wt% PEGDA 575, indicating that the polymer softened. The Young’s Modulus was further reduced to 15 MPa under physiologic conditions. The fracture strain, a measure of stretchability, increased from 55% to 92% with the addition of 5 wt% PEGDA 575. A thermomechanical analysis further confirmed that PEGDA could be used to tune the polymer’s glass transition temperature (Tg). Moreover, our polymer exhibited shape memory properties. Our results suggested that thiol-ene/acrylate polymers are a promising new class of materials for biomedical applications requiring flexibility, stretchability, and shape memory properties.

Do you want to read more? The full publication can be found here:

C. Chitrakar, M.A. Torres, P.E. Rocha-Flores, Q. Hu, M. Ecker, Multifaceted Shape Memory Polymer Technology for Biomedical Application: Combining Self-Softening and Stretchability Properties. Polymers202315, 4226. 

https://doi.org/10.3390/polym15214226

New Publication: Thermo/hydration responsive shape memory polymers with enhanced hydrophilicity for biomedical applicationsNew Publication:

A collaborative project with the Voit Group from UT Dallas. Congratulations, Qichan, for this contribution!

Abstract

Thiol-ene/acrylate shape memory polymers (SMPs) have sufficient stiffness for facile insertion and precision placement and soften after exposure to physiological conditions to reduce the mechanical mismatch with body tissue. As a result, they have demonstrated excellent potential as substrates for various flexible bioelectronic devices, such as cochlear implants, nerve cuffs, cortical probes, plexus blankets, and spinal cord stimulators. To enhance the shape recovery properties and softening effect of SMPs under physiological conditions, we designed and implemented a new class of SMPs as bioelectronics substrates. In detail, we introduced dopamine acrylamide (DAc) as a hydrophilic monomer into a current thiol-ene polymer network. Dry and soaked dynamic mechanical analyses were performed to evaluate the thermomechanical properties, softening kinetics under wet conditions, and shape recovery properties. Modification of SMPs by DAc provided an improved softening effect and shape recovery speed under physiological conditions. Here, we report a new strategy for designing SMPs with enhanced shape recovery properties and lower moduli than previously reported SMPs under physiological conditions without sacrificing stiffness at room temperature by introducing a hydrophilic monomer.

Do you want to read more? The full publication can be found here:

https://iopscience.iop.org/article/10.1088/1361-665X/aca576

New Publication: Recyclable, Biobased Photoresins for 3D Printing Through Dynamic Imine Exchange

This work was led by the Smaldone Group from UT Dallas. Lauren and Chandani completed some of the thermomechanical characterizations.

Abstract

Transimination reactions are highly effective dynamic covalent reactions to enable reprocessability in thermosets, as they can undergo exchange without the need for catalysts, by exposing the materials to external stimuli such as heat. In this work, a series of five biobased vanillin-derived resin formulations consisting of vanillin acrylate with vanillin methacrylate-functionalized Jeffamines were synthesized and 3D-printed using digital light projection (DLP). The resulting thermosets displayed a range of mechanical properties (Young’s modulus 2.05–332 MPa), which allow for an array of applications. The materials we obtained have self-healing abilities, which were characterized by scratch healing tests. Additionally, dynamic transimination reactions enable these thermosets to be reprocessed when thermally treated above their glass transition temperatures under high pressures using a hot press. Due to the simple synthetic procedures and the readily available commercial Jeffamines, these materials will aid in promoting a shift to materials with predominantly biobased content and help drift away from polymers made from non-renewable resources.

Do you want to read more? The full publication can be found here: https://pubs.acs.org/doi/full/10.1021/acssuschemeng.2c03541

New publication: Flexible and Stretchable Bioelectronics

The first publication of 2022 is now published and online available! Congratulations to Chandani, Eric, and Lauren for their great review paper on stretchable and flexible bioelectronics!

Abstract

Medical science technology has improved tremendously over the decades with the invention of robotic surgery, gene editing, immune therapy, etc. However, scientists are now recognizing the significance of ‘biological circuits’ i.e., bodily innate electrical systems for the healthy functioning of the body or for any disease conditions. Therefore, the current trend in the medical field is to understand the role of these biological circuits and exploit their advantages for therapeutic purposes. Bioelectronics, devised with these aims, work by resetting, stimulating, or blocking the electrical pathways. Bioelectronics are also used to monitor the biological cues to assess the homeostasis of the body. In a way, they bridge the gap between drug-based interventions and medical devices. With this in mind, scientists are now working towards developing flexible and stretchable miniaturized bioelectronics that can easily conform to the tissue topology, are non-toxic, elicit no immune reaction, and address the issues that drugs are unable to solve. Since the bioelectronic devices that come in contact with the body or body organs need to establish an unobstructed interface with the respective site, it is crucial that those bioelectronics are not only flexible but also stretchable for constant monitoring of the biological signals. Understanding the challenges of fabricating soft stretchable devices, we review several flexible and stretchable materials used as substrate, stretchable electrical conduits and encapsulation, design modifications for stretchability, fabrication techniques, methods of signal transmission and monitoring, and the power sources for these stretchable bioelectronics. Ultimately, these bioelectronic devices can be used for wide range of applications from skin bioelectronics and biosensing devices, to neural implants for diagnostic or therapeutic purposes.

Do you want to read more? The full publication can be found here.

New publication: Incorporation of Novel Elements in Bioactive Glass Compositions to Enhance Implant Performance

The third publication this year from our lab is now online available. Joy-anne and Olanrewaju have worked together on this book chapter for ‘Bioactive Glass – Recent Advances, New Perspectives and Applications’ from IntechOpen. A hard copy of this book will be available later this year.

Abstract

Increasing popularities of bioactive-glasses and their potential medical applications have led to countless studies into improving their material characteristics and overall performance. Some scientists hope to create new bioactive-glass compositions, while others seek to merely modify existing ones such as the novel 45S5 bioactive-glass composition; created by Dr. Larry Hench. These modifications aim to address potential complications that may arise at a site following implantation such as bacterial infections. In other cases, the incorporation of a selected element or compound may aim to improve the implant functioning by increasing cell proliferation. Although possibilities are plentiful, researchers avoid compromising the typical bioactive glass characteristics when doping with elements such as silver, or gold to achieve additional properties. This chapter elaborates on the incorporation of popular elements by doping bioactive-glass compositions to introduce desired properties based on the implant application.

Do you want to read more? The full publication can be found here.