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1. Fabrication and Characterization of Quad-Component Bioinspired Hydrogels to Model Elevated Fibrin Levels in Central Nervous Tissue Scaffolds

   https://doi.org/10.3390/gels10030203  

   Diaz-Lasprilla, Ana M; McKee, Meagan; Jimenez-Vergara, Andrea C; Ravi, Swathisri; Bellamy, Devon; Ortega, Wendy; Crosby, Cody O; Steele, Jennifer; Plascencia-Villa, Germán; Perry, George; et al (March 2024, Gels)

   Kakehashi, Rie; Yamashita, Yuji (Ed.)

   Multicomponent interpenetrating polymer network (mIPN) hydrogels are promising tissue-engineering scaffolds that could closely resemble key characteristics of native tissues. The mechanical and biochemical properties of mIPNs can be finely controlled to mimic key features of target cellular microenvironments, regulating cell-matrix interactions. In this work, we fabricated hydrogels made of collagen type I (Col I), fibrin, hyaluronic acid (HA), and poly (ethylene glycol) diacrylate (PEGDA) using a network-by-network fabrication approach. With these mIPNs, we aimed to develop a biomaterial platform that supports the in vitro culture of human astrocytes and potentially serves to assess the effects of the abnormal deposition of fibrin in cortex tissue and simulate key aspects in the progression of neuroinflammation typically found in human pathologies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and tissue trauma. Our resulting hydrogels closely resembled the complex modulus of AD human brain cortex tissue (~7.35 kPa), promoting cell spreading while allowing for the modulation of fibrin and hyaluronic acid levels. The individual networks and their microarchitecture were evaluated using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Human astrocytes were encapsulated in mIPNs, and negligible cytotoxicity was observed 24 h after the cell encapsulation. 

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2. Engineering Adhesive Hydrogels for Hemostasis and Vascular Repair

   https://doi.org/10.3390/polym17070959  

   Jeon, Juya; Subramani, Shri Venkatesh; Lee, Kok Zhi; Elizondo-Benedetto, Santiago; Zayed, Mohamed Adel; Zhang, Fuzhong (April 2025, Polymers)

   Adhesive hydrogels with tunable mechanical properties and strong adhesion to wet, dynamic tissues have emerged as promising materials for tissue repair, with potential applications in wound closure, hemorrhage control, and surgical adhesives. This review highlights the key design principles, material classifications, and recent advances in adhesive hydrogels designed for vascular repair. The limitations of existing adhesive hydrogels, including insufficient mechanical durability, suboptimal biocompatibility, and challenges in targeted delivery, are critically evaluated. Furthermore, innovative strategies—such as incorporating self-healing capabilities, developing stimuli-responsive systems, integrating functional nanocomposites, and employing advanced fabrication techniques like 3D bioprinting—are discussed to enhance adhesion, mechanical stability, and vascular tissue regeneration. While significant progress has been made, further research and optimization are necessary to advance these materials toward clinical translation, offering a versatile and minimally invasive alternative to traditional vascular repair techniques. 

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3. Soft, strong, tough, and durable protein-based fiber hydrogels

   https://doi.org/10.1073/pnas.2213030120  

   Wang, Mingkun; Sun, Shuofei; Dong, Gening; Long, Feifei; Butcher, Jonathan T. (February 2023, Proceedings of the National Academy of Sciences)

   Load-bearing soft tissues normally show J-shaped stress–strain behaviors with high compliance at low strains yet high strength at high strains. They have high water content but are still tough and durable. By contrast, naturally derived hydrogels are weak and brittle. Although hydrogels prepared from synthetic polymers can be strong and tough, they do not have the desired bioactivity for emerging biomedical applications. Here, we present a thermomechanical approach to replicate the combinational properties of soft tissues in protein-based photocrosslinkable hydrogels. As a demonstration, we create a gelatin methacryloyl fiber hydrogel with soft tissue-like mechanical properties, such as low Young’s modulus (0.1 to 0.3 MPa), high strength (1.1 ± 0.2 MPa), high toughness (9,100 ± 2,200 J/m 3 ), and high fatigue resistance (2,300 ± 500 J/m 2 ). This hydrogel also resembles the biochemical and architectural properties of native extracellular matrix, which enables a fast formation of 3D interconnected cell meshwork inside hydrogels. The fiber architecture also regulates cellular mechanoresponse and supports cell remodeling inside hydrogels. The integration of tissue-like mechanical properties and bioactivity is highly desirable for the next-generation biomaterials and could advance emerging fields such as tissue engineering and regenerative medicine. 

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4. Mechanically and Chemically Defined PEG Hydrogels Improve Reproducibility in Human Cardioid Development

   https://doi.org/10.1002/adhm.202403997  

   Song, Yuanhui; Seitz, Michael; Kowalczewski, Andrew; Mai, Nhu Y; Jain, Era; Yang, Huaxiao; Ma, Zhen (June 2025, Advanced Healthcare Materials)

   Abstract Cardioids are 3D self‐organized heart organoids directly derived from induced pluripotent stem cells (hiPSCs) aggregates. The growth and culture of cardioids is either conducted in suspension culture or heavily relies on Matrigel encapsulation. Despite the significant advancements in cardioid technology, reproducibility remains a major challenge, limiting their widespread use in both basic research and translational applications. Here, for the first time, we employed synthetic, matrix metalloproteinase (MMP)‐degradable polyethylene glycol (PEG)‐based hydrogels to define the effect of mechanical and biochemical cues on cardioid development. Successful cardiac differentiation is demonstrated in all the hydrogel conditions, while cardioid cultured in optimized PEG hydrogel (3 wt.% PEG‐2mM RGD) underwent similar morphological development and comparable tissue functions to those cultured in Matrigel. Matrix stiffness and cell adhesion motif play a critical role in cardioid development, nascent chamber formation, contractile physiology, and endothelial cell gene enrichment. More importantly, synthetic hydrogel improved the reproducibility in cardioid properties compared to traditional suspension culture and Matrigel encapsulation. Therefore, PEG‐based hydrogel has the potential to be used as an alternative to Matrigel for human cardioid culture in a variety of clinical applications including cell therapy and tissue engineering. 

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5. Quantifying and Controlling the Proteolytic Degradation of Cell Adhesion Peptides

   https://doi.org/10.1021/acsbiomaterials.4c00736  

   Rozans, Samuel J; Moghaddam, Abolfazl Salehi; Wu, Yingjie; Atanasoff, Kayleigh; Nino, Liliana; Dunne, Katelyn; Pashuck, E Thomas (August 2024, ACS Biomaterials Science & Engineering)

   Peptides are widely used within biomaterials to improve cell adhesion, incorporate bioactive ligands, and enable cell-mediated degradation of the matrix. While many of the peptides incorporated into biomaterials are intended to be present throughout the life of the material, their stability is not typically quantified during culture. In this work, we designed a series of peptide libraries containing four different N-terminal peptide functionalizations and three C-terminal functionalizations to better understand how simple modifications can be used to reduce the nonspecific degradation of peptides. We tested these libraries with three cell types commonly used in biomaterials research, including mesenchymal stem/stromal cells (hMSCs), endothelial cells, and macrophages, and quantified how these cell types nonspecifically degraded peptides as a function of terminal amino acid and chemistry. We found that peptides in solution which contained N-terminal amines were almost entirely degraded by 48 h, irrespective of the terminal amino acid, and that degradation occurred even at high peptide concentrations. Peptides with C-terminal carboxylic acids also had significant degradation when cultured with the cells. We found that simple modifications to the termini could significantly reduce or completely abolish nonspecific degradation when soluble peptides were added to cells cultured on tissue culture plastic or within hydrogel matrices, and that functionalizations which mimicked peptide conjugations to hydrogel matrices significantly slowed nonspecific degradation. We also found that there were minimal differences in peptide degradation across cell donors and that sequences mimicking different peptides commonly used to functionalize biomaterials all had significant nonspecific degradation. Finally, we saw that there was a positive trend between RGD stability and hMSC spreading within hydrogels, indicating that improving the stability of peptides within biomaterial matrices may improve the performance of engineered matrices. 

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