Functional Nanomaterials on 2D Surfaces and in 3D Nanocomposite Hydrogels for Biomedical Applications

An emerging approach to improve the physicobiochemical properties and the multifunctionality of biomaterials is to incorporate functional nanomaterials (NMs) onto 2D surfaces and into 3D hydrogel networks. This approach is starting to generate promising advanced functional materials such as self-assembled monolayers (SAMs) and nanocomposite (NC) hydrogels of NMs with remarkable properties and tailored functionalities that are beneficial for a variety of biomedical applications, including tissue engineering, drug delivery, and developing biosensors. A wide range of NMs, such as carbon-, metal-, and silica-based NMs, can be integrated into 2D and 3D biomaterial formulations due to their unique characteristics, such as magnetic properties, electrical properties, stimuli responsiveness, hydrophobicity/hydrophilicity, and chemical composition. The highly ordered nano- or microscale assemblies of NMs on surfaces alter the original properties of the NMs and add enhanced and/or synergetic and novel features to the final SAMs of the NM constructs. Furthermore, the incorporation of NMs into polymeric hydrogel networks reinforces the (soft) polymer matrix such that the formed NC hydrogels show extraordinary mechanical properties with superior biological properties

Photocurable silk fibroin-based tissue sealants with enhanced adhesive properties for the treatment of corneal perforations

Corneal defects are associated with corneal tissue engineering in terms of vision loss. The treatment of corneal defects is an important clinical challenge due to a uniform corneal thickness and the apparent lack of regenerative ability. In this work, we synthesized a biocompatible and photocrosslinkable ocular tissue adhesive composite hydrogel prepared by using methacrylated gelatin (GelMA), which is called the most favorable derivative of gelatin used as a tissue adhesive, silk fibroin (SF), and GelMA/SF (GS) with high adhesion behaviours for use in corneal injuries. The adhesion behaviours of the materials prepared in the presence of silk fibroin were improved. Importantly, the effect of different UV curing times on the adhesion properties of the prepared materials was also investigated. The prepared GS tissue adhesives showed high physiological adhesion. GS can be modulated to increase its adhesive strength up to 3 times compared to G. GS was also found to be biocompatible and have a high healing potential. In addition, the obtained transmission value of GS is also close to that of the human cornea. GS supported cellular adhesion and proliferation. The burst pressure strength for fresh cornea of the GS-60s sealants (144.5 ± 13 kPa) was determined to be higher than that of the G-60s sealants (52.6 ± 33.5 kPa)

In situ formation of biocompatible and ductile protein-based hydrogels via Michael addition reaction and visible light crosslinking

Keratin, a biological polymer with high sulfur content, is the main component of hair, feathers and wool. Human hair is the cheapest natural source of keratin. In this study, an optimized and very effective reduction reaction method was used to obtain keratin from human hair. During this process, the disulfide bridge of keratin was reduced in the presence of sodium sulfide to form free sulfhydryl (thiols) that would act as a strong nucleophile. The results of FTIR spectroscopy, Tricine-SDS-PAGE and MALDI-TOF/MS verified the successful extraction of the reduced human hair keratin. A well-interconnected structure with three-dimensional (3D) scaffolds was prepared using keratin and methacrylated gelatin (GelMA), KeratinGel, for tissue engineering and other biomedical applications. KeratinGel hydrogels were in situ prepared via Michael addition reaction and visible light crosslinking. Two complementary crosslinking reactions were combined to enhance the network structure and provide ductility. With the targeted two-step method, the reactivity of vinyl groups of GelMA to photocrosslinking and thiol groups in keratin to the Michael addition reaction was exploited. Rheological monitoring of the Michael addition reaction was performed for KeratinGel hydrogels in a basic reaction environment at pH 7.4 with a constant concentration of GelMA (10% w/v) and different amounts of reduced human hair keratin (5, 7.5 and 10% w/v) at room temperature. The physical properties, swelling and degradation rates of KeratinGel hydrogels were determined to understand their suitability for tissue regeneration. We finalize that KeratinGel hydrogels would be better in minimally invasive surgeries, soft tissue engineering, especially with in situ gelling features, and favourable for the preparation of complex shapes and applications

Engineering Tough, Injectable, Naturally Derived, Bioadhesive Composite Hydrogels

Engineering mechanically robust bioadhesive hydrogels that can withstand large strains may open new opportunities for the sutureless sealing of highly stretchable tissues. While typical chemical modifications of hydrogels, such as increasing the functional group density of crosslinkable moieties and blending them with other polymers or nanomaterials have resulted in improved mechanical stiffness, the modified hydrogels have often exhibited increased brittleness resulting in deteriorated sealing capabilities under large strains. Furthermore, highly elastic hydrogels, such as tropoelastin derivatives are highly expensive. Here, gelatin methacryloyl (GelMA) is hybridized with methacrylate-modified alginate (AlgMA) to enable ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid hydrogels provide a photocrosslinkable, injectable, and bioadhesive platform with an excellent toughness that can be tailored using divalent cations, such as calcium. This class of hybrid biopolymers with more than 600% improved toughness compared to GelMA may set the stage for durable, mechanically resilient, and cost-effective tissue sealants. This strategy to increase the toughness of hydrogels may be extended to other crosslinkable polymers with similarly reactive moieties