NDI based C2-symmetric Chiral Supramolecular Hydrogels Towards Enhanced Conductivity.

To comprehend the significance of improved conductive properties in C2-symmetric hydrogels, it is vital to investigate how non-gelating achiral functional group isomers influence the conductivity of such supramolecular hydrogels, whereas understanding the major driving forces behind this regulatory process is first and foremost. Herein, we report a hydrogel system containing tryptophan-conjugated NDI as the backbone (L/D-NTrp), enabling effective supramolecular assembly with the bipyridyl functional group isomers. This co-assembly behavior results in materials with exceptional mechanical properties and high conductivities, surpassing most previously reported C2-symmetrical hydrogels, as well as the ability to form controlled morphologies. Notably, the co-hydrogels displayed an eight-fold increase in mechanical strength, making them more robust and resistant to deformation compared to the original gel. Additionally, all hydrogels exhibited favorable electrical conductivity, with the co-assembled hydrogels showcasing notable performance, making them a promising candidate for use in electronic devices and sensors. This report lays the foundation for further investigation into the properties and potential applications of L/D-NTrp compound in the range of fields, including drug delivery, tissue engineering, and electronics.

Autoclavable Albumin-Based Cryogels with Uncompromising Properties.

The development of autoclavable hydrogels has been driven by the need for materials that can withstand the rigors of sterilization without compromising their properties or functionality. Many conventional hydrogels cannot withstand autoclave treatment owing to the breakdown of their composition or structure under the high-temperature and high-pressure environment of autoclaving. Here, the effect of autoclaving on the physical, mechanical, and biological properties of bovine serum albumin methacryloyl (BSAMA) cryogels at three protein concentrations (3, 5, and 10%) was extensively studied. We found that BSAMA cryogels at three concentrations remained little changed after autoclaving in terms of gross shape, pore structure, and protein secondary structure. Young's modulus of autoclaved BSAMA cryogels (BSAMAA) at low concentrations (3 and 5%) was similar to that of BSAMA cryogels, whereas 10% BSAMAA exhibited a higher Young's modulus value, compared with 10% BSAMA. Interestingly, BSAMAA cryogels prolonged degradation. Importantly, cell viability, drug release, and hemolytic behaviors were found to be similar among the pre- and post-autoclaved cryogels. Above all, autoclaving proved to be more effective in sterilizing BSAMA cryogels from bacteria contamination than UV and ethanol treatments. Thus, autoclavable BSAMA cryogels with uncompromising properties would be useful for biomedical applications.

Emerging albumin hydrogels as personalized biomaterials.

Developing biomaterials-based tissue engineering scaffolds with personalized features and intrinsic biocompatibility is appealing and urgent. Through utilizing various strategies, albumin, as the most abundant protein in plasma, could be fabricated into sustainable, cost-effective, and potentially personalized hydrogels that would display enormous biological applications. To date, much of the albumin-based research is primarily engrossed in using albumin as a therapeutic molecule or a drug carrier, not much as a scaffold for tissue engineering. For this reason, we have come up with a detailed and insightful review of recent progress in albumin-based hydrogels having an emphasis on production techniques, material characteristics, and biological uses. It is envisioned that albumin-based scaffolds would be appealing and useful platforms to meet current tissue engineering needs and achieve the goal of clinical translation to benefit patients. STATEMENT OF SIGNIFICANCE: The creation of autologous material-based scaffolds is a potential method for preventing immunological reactions and obtaining the best therapeutic results. Patient-derived albumin hydrogels may consequently provide improved opportunities for personalized treatment due to their abundant supply and minimal immunogenicity. To provide a detailed and insightful summary on albumin-based hydrogels, this review includes latest comprehensive information on their preparation procedures, features, and applications in 3D printing and other biomedical applications. The challenges, along with the future potential for implementing albumin-based hydrogels in clinics, have also been addressed.

Human Albumin-Based Hydrogels for Their Potential Xeno-Free Microneedle Applications.

Nowadays, hydrogels-based microneedles (MNs) have attracted a great interest owing to their outstanding qualities for biomedical applications. For the fabrication of hydrogels-based microneedles as tissue engineering scaffolds and drug delivery carriers, various biomaterials have been tested. They are required to feature tunable physiochemical properties, biodegradability, biocompatibility, nonimmunogenicity, high drug loading capacity, and sustained drug release. Among biomaterials, human proteins are the most ideal biomaterials for fabrication of hydrogels-based MNs; however, they are mechanically weak and poorly processible. To the best of the knowledge, there are no reports of xeno-free human protein-based MNs so far. Here, human albumin-based hydrogels and microneedles for tissue engineering and drug delivery by using relatively new processible human serum albumin methacryloyl (HSAMA) are engineered. The resultant HSAMA hydrogels display tunable mechanical properties, biodegradability, and good biocompatibility. Moreover, the xeno-free HSAMA microneedles display a sustained drug release profile and significant mechanical strength to penetrate the model skin. In vitro, they also show good biocompatibility and anticancer efficacy. Sustainable processible human albumin-based biomaterials may be employed as a xeno-free platform in vivo for tissue engineering and drug delivery in clinical trials in the future.

Mussel-Inspired Surface Functionalization of Porous Albumin Cryogels Supporting Synergistic Antibacterial/Antioxidant Activity and Bone-Like Apatite Formation.

A crucial method for adding new functions to current biomaterials for biomedical applications has been surface functionalization via molecular design. Mussel-inspired polydopamine (PDA) has generated much attention as a facile method for the functionalization of biomaterials because of its substantial independence in deposition, beneficial cell interactions, and significant responsiveness aimed at secondary functionalization. Because of their porous structure, the bovine serum albumin methacryloyl (BSAMA)-BM cryogels were functionalized with PDA (BM-PDA), which may reproduce the architecture and biological purpose of the natural extracellular environment. Excellent antioxidative and antibacterial qualities, improved mineralization, and better cell responsiveness were all demonstrated by BM-PDA. BM-PDA scaffolds maintained their linked and uniform pores after functionalization, which can make it easier for nutrients to be transported during bone repair. As a result, hydroxyapatite (HA)-coated BM* and BM-PDA* cryogels were created through successive mineralization with the goal of mineralized bone tissue repair. The heterogeneous nucleation and surface roughness contributed to rod-like apatite production in BM-PDA* cryogels whereas BM* cryogels were made up of plate-like HA morphologies. Analysis results showed that after five cycles, the mineral contents were around 57% and the HA units remained equally dispersed on the surface of BM-PDA* with a Ca/P ratio of 1.63. Other natural polymer-based cryogels can be coated using this general, rapid, and simple PDA coating technique and utilized as implants for bone tissue engineering. Future clinical uses of albumin cryogels for bone tissue engineering will advance as a result of additional in-vivo testing of such PDA-coated cryogels.

Facile Fabrication of Transparent and Opaque Albumin Methacryloyl Gels with Highly Improved Mechanical Properties and Controlled Pore Structures.

For porous protein scaffolds to be employed in tissue-engineered structures, the development of cost-effective, macroporous, and mechanically improved protein-based hydrogels, without compromising the original properties of native protein, is crucial. Here, we introduced a facile method of albumin methacryloyl transparent hydrogels and opaque cryogels with adjustable porosity and improved mechanical characteristics via controlling polymerization temperatures (room temperature and -80 °C). The structural, morphological, mechanical, and physical characteristics of both porous albumin methacryloyl biomaterials were investigated using FTIR, CD, SEM, XRD, compression tests, TGA, and swelling behavior. The biodegradation and biocompatibility of the various gels were also carefully examined. Albumin methacryloyl opaque cryogels outperformed their counterpart transparent hydrogels in terms of mechanical characteristics and interconnecting macropores. Both materials demonstrated high mineralization potential as well as good cell compatibility. The solvation and phase separation owing to ice crystal formation during polymerization are attributed to the transparency of hydrogels and opacity of cryogels, respectively, suggesting that two fully protein-based hydrogels could be used as visible detectors/sensors in medical devices or bone regeneration scaffolds in the future.

Novel biohybrid spongy scaffolds for fabrication of suturable intraoral graft substitutes.

Despite the fact that classic autograft is the gold standard material for periodontal plastic surgery, it has some drawbacks, including the need for a second surgical site and the scarcity of palatal donor tissues. However, only a few research works on the manufacturing of bioengineered intraoral connective tissue grafts have been conducted. In this work, porous bovine serum albumin methacryloyl/gelatin methacryloyl (BG) biohybrid scaffolds were developed for super-elasticity, shape recovery, suturability for persistent stability, sufficient scaffolding function, and convenient manipulating characteristics to fabricate an intraoral graft substitute with superb stability to resist frequent dynamic forces caused by functional movement (speaking, masticating, and swallowing). Furthermore, in a 3D cell culture assay, BG scaffolds demonstrated excellent cell adhesion and proliferation of L929 cells. In addition, the BG scaffolds were able to release Ibuprofen in a controlled manner for postoperative recovery. The use of a low-cost, optimized cryogelation technique for functional biomacromolecules offers up new possibilities to develop promising scaffolds for dental clinical settings.

Comparison of globular albumin methacryloyl and random-coil gelatin methacryloyl: Preparation, hydrogel properties, cell behaviors, and mineralization.

Bovine serum albumin methacryloyl (BSAMA) is a newly emerging photocurable globular protein-based material whereas gelatin methacryloyl (GelMA) is one of the most popular photocurable fibrous protein-based materials. So far, the influence of their different structural conformations as building blocks on hydrogel properties and mineral deposition has not been investigated. Here, we compared their differences in structures, gelation kinetics, hydrogel properties, mineralization, and cell behaviors. BSAMA maintained a stable globular structure while GelMA exhibited temperature-sensitive conformations (4 - 37 °C). BSAMA displayed slower gelation kinetics and much more retarded enzymatic degradation compared to GelMA. Photocurable BSAMA (6.41 - 390.95 kPa) and GelMA hydrogels (36.09 - 199.70 kPa) exhibited tunable mechanical properties depending on their concentrations (10 - 20%). Interestingly, BSAMA hydrogels mineralized needle-like apatite (Ca/P: 1.409) with higher crystallinity compared to GelMA hydrogels (Ca/P: 1.344). BSAMA and GelMA supported satisfactory cell (MC3T3-L1) viability of 99.43 ± 0.57% and 97.14 ± 0.69%, respectively. However, BSAMA gels were less favorable to cell proliferation and migration than GelMA gels. In serum-free environments, cells on GelMA displayed a higher amount of attachment, a more elongated shape, and a longer protrusion compared to those on BSAMA (p < 0.01) during the early adhesion.

Supramolecular Hydrogels with Tunable Chirality for Promising Biomedical Applications.

Chirality exits from molecular-level, supramolecular, and nanoscaled helical structures to the macroscopic level in biological life. Among these various levels, as the central structural motifs in living systems (e.g., double helix in DNA, α-helix, ß-sheet in proteins), supramolecular helical systems arising from the asymmetrical spatial stacking of molecular units play a crucial role in a wide diversity of biochemical reactions (e.g., gene replication, molecular recognition, ion transport, enzyme catalysis, and so on). However, the importance of supramolecular chirality and its potential biofunctions has not yet been fully explored. Thus, generating chiral assembly to transfer nature's chiral code to artificial biomaterials is expected to be utilized for developing novel functional biomaterials. As one of the most commonly used biomaterials, supramolecular hydrogels have attracted considerable research interest due to their resemblance to the structure and function of the native extracellular matrix (ECM). Therefore, the performance and manipulation of chiral assembled nanoarchitectures in supramolecular hydrogels may provide useful insights into understanding the role of supramolecular chirality in biology.In this Account, recent progress on chiral supramolecular hydrogels is presented, including how to construct and regulate assembled chiral nanostructures in hydrogels with controllable handedness and then use them to develop chiral hydrogels that could be applied in biology, biochemistry, and medicine. First, a brief introduction is provided to present the basic concept related to supramolecular chirality and the importance of supramolecular chirality in living systems. The chiral assemblies in supramolecular hydrogels are strongly driven by noncovalent interactions between molecular building blocks (such as hydrogen bonding, π-π stacking, hydrophobic, and van der Waals interactions). Consequently, the handedness of these chiral assemblies can be regulated by many extra stimuli including solvents, temperature, pH, metal ions, enzymes, and photoirradiation, which is presented in the second section. This manipulation of the chirality of nanoarchitectures in supramolecular hydrogels can result in the development of potential biofunctions. For example, specific supramolecular chirality-induced biological phenomena (such as controlled cell adhesion, proliferation, differentiation, apoptosis, protein adsorption, drug delivery, and antibacterial adhesion) are presented in detail in the third section. Finally, the outlook of open challenges and future developments of this rapidly evolving field is provided. This account that highlights the diverse chirality-dependent biological phenomena not only helps us to understand the importance of chirality in life but also provides new ideas for designing and preparing chiral materials for more bioapplications.

Antimicrobial Activity with Enhanced Mechanical Properties in Phenylalanine-Based Chiral Coassembled Hydrogels: The Influence of Pyridine Hydrazide Derivatives.

Hydrazide derivatives are known to display a wide range of biological properties including antimicrobial activities, hence making them desirable candidates for soft biomaterials. Herein, we report chiral supramolecular coassembled hydrogels obtained from two phenylalanine gelators (L/DPF and B2L/D) and two dicarbohydrazide molecules (pyridine-2,6-dicarbohydrazide (PDH) and (2,2'-bipyridine)-5,5'-dicarbohydrazide (BDH)) that exhibited enhanced mechanical properties, chirality modulation, and antimicrobial activity. Four lines of coassembled hydrogels were obtained (i.e., L/DPF-PDH, L/DPF-BDH, B2L/D-PDH, and B2L/D-BDH) through hydrogen bonding and π-π stacking with some level of an interpenetrating network, as revealed by the structural characterization analysis. Mechanical properties were significantly improved, especially in the case of hybrid gels involving BDH, with improved average elastic modulus (G') values of 3430 and 3167 Pa for DPF-BDH and B2D-BDH (1:3, molar concentration) over 140 and 1680 Pa for DPF and B2D gelators, respectively. This was attributed to the improved π-π stacking and interpenetrating network due to the bipyridine group and its ease to form fibrous precipitates in the process of heating and cooling to room temperature. PDH, on the other hand, was able to modulate chirality in the L/DPF gelator due to its more planar and less bulky nature and showed antimicrobial activity against Pseudomonas aeruginosa (Gram-negative). Interestingly, when PDH was coassembled with the B2L/D gelator, the hybrid gels exhibited antimicrobial activity against Staphylococcus aureus (Gram-positive) and P. aeruginosa (Gram-negative) by virtue of a synergistic effect of the gelator and the azomethine group of PHD. Hence, by moving from bipyridine (BDH) to pyridine (PDH) as a core structure in the hydrazide molecules, the resulting hybrid hydrogels exhibited desirable properties of antimicrobial activity and improved mechanical attributes.