Functionalized TiO2 Based Nanomaterials for Biomedical Applications

As baby boomers age, diabetes mellitus, cancer, osteoarthritis, cardiovascular diseases, and orthopedic disorders are more widespread and the demand for better biomedical devices and functional biomaterials is increasing rapidly. Owing to the good biocompatibility, chemical stability, catalytic efficiency, plasticity, mechanical properties, as well as strength‐to‐weight ratio, titanium dioxide (TiO₂) based nanostructured materials are playing important roles in tissue reconstruction and diagnosis of these diseases. Here, recent advance in the research of nanostructured TiO₂ based biomaterials pertaining to bone tissue engineering, intravascular stents, drug delivery systems, and biosensors is described.     

Marine-Derived Hydrogels for Biomedical Applications

Marine organisms provide novel and broad sources for the preparations and applications of biomaterials. Since the urgent requirement of bio-hydrogels to mimic tissue extracellular matrix (ECM), the natural biomacromolecule hydrogels derived from marine sources have received increasing attention. Benefiting from their outstanding bioactivity and biocompatibility, many attempts have been made to reconstruct ECM components by applying marine-derived natural hydrogels. Moreover, marine hydrogels have been successfully applied in biomedicine by means of microfluidics, electrospray, and bioprinting. In this review, the classification and characteristics of marine-derived hydrogels are summarized. In particular, their role in the development of biomaterials is also introduced. Then, the recent advances in bio-fabrication strategies for various hydrogel materials are focused upon. Besides, the influences of hydrogel types on their functions in biomedical applications are discussed in depth. Finally, critical reflections on the limitations and future development of marine-derived hydrogels are presented.     

Enhancing the Solubility and Transdermal Delivery of Drugs Using Ionic Liquid-In-Oil Microemulsions

The development of hydrophobic drug and protein delivery carriers remains a challenge. To synthesize L-(-)-carnitine-based ionic liquid (IL), this study applies the density functional theory to investigate the hydrogen bonds and van der Waals force that govern L-(-)-carnitine-based IL formation. An ionic liquid-in-oil microemulsion (IL/O ME) is then developed to facilitate the transdermal delivery of proteins and increase the solubility of drugs. IL/O ME is prepared using isopropyl myristate (IPM), Tween 80/Span 20, and L-(-)-carnitine-based IL. The skin permeation studies conducted using mouse skin show that the insulin permeation percentage of the developed IL/O ME is 3.55 folds higher than that of phosphate-buffered saline and 2.91 folds better than that of a hydrophilic L-(-)-carnitine-based IL. In addition, the solubility of two drug molecules, that is, rosiglitazone and bezafibrate, in IL/O ME is at least 49.28 folds higher than their solubility in water or IPM. Therefore, IL/O ME can significantly improve the solubility of drugs and increase the permeability of proteins (e.g., insulin), thus demonstrating a promising potential as a delivery carrier.     

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.     

Programmable Biopolymers for Advancing Biomedical Applications of Fluorescent Nanodiamonds

A versatile biopolymer platform for advancing nanodiamonds (NDs) as unique magnetooptic materials for biomedical applications is presented here. Precision biopolymer coatings are designed by chemical reprogramming the functionalities of serum albumin via a straightforward synthesis protocol. Such biopolymers offer high biocompatibility and precise modification with various functional entities due to the large number of available reactive amino acid residues. Premodification of these biopolymers provides a convenient approach to customized surface functionalization of NDs. As an example, the anticancer drug doxorubicin (DOX) is conjugated to the biopolymer with high reproducibility and full characterization. The biopolymer‐coated NDs reveal excellent colloidal stabilities in all physiological media tested, even after loading with high numbers of hydrophobic DOX. The intracellular distribution of NDs and DOX is analyzed in living cells by recording the fluorescence spectra in different cellular compartments, which proves efficient intracellular release of DOX from the carrier. Studies in vitro as well as in a chick tumor xenograft model reveal efficient antitumor effects. The facile and versatile biopolymer coating strategy reported herein will greatly accelerate the availability of customized NDs with reliable and reproducible features to exploit their great potential in single molecular bioimaging, in vivo biosensing, and high resolution quantum optics.     

2D Covalent Organic Frameworks for Biomedical Applications

Covalent organic frameworks (COFs) are an emerging class of organic crystalline polymers with well‐defined molecular geometry and tunable porosity. COFs are formed via reversible condensation of lightweight molecular building blocks, which dictate its geometry in two or three dimensions. Among COFs, 2D COFs have garnered special attention due to their unique structure composed of two‐dimensionally extended organic sheets stacked in layers generating periodic columnar π‐arrays, functional pore space, and their ease of synthesis. These unique features in combination with their low density, high crystallinity, large surface area, and biodegradability have made them an excellent candidate for a plethora of applications ranging from energy to biomedical sciences. In this article, the evolution of 2D COFs is briefly discussed in terms of different types of chemical linkages, synthetic strategies of bulk and nanoscale 2D COFs, and their tunability from a biomedical perspective. Next, the biomedical applications of 2D COFs specifically for drug delivery, phototherapy, biosensing, bioimaging, biocatalysis, and antibacterial activity are summarized. In addition, current challenges and emerging approaches in designing 2D COFs for advanced biomedical applications are discussed.     

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.     

Ionic Liquids and Deep Eutectic Solvents for Enhanced Delivery of Antibodies in the Gastrointestinal Tract

Monoclonal antibodies (mAbs) are currently used for the treatment of numerous conditions including cancer, psoriasis, arthritis, and atopic dermatitis, among others. All mAbs are currently administered by either intravenous or subcutaneous injections. Herein, the use of a novel ionic liquid and deep eutectic solvent, choline and glycolate (CGLY), as a platform for gastrointestinal administration of therapeutic antibodies is reported. CGLY maintains the stability and structure of TNFα antibody. CGLY significantly enhances paracellular transport of TNFα antibody in vitro. CGLY also reduces the viscosity of the intestinal mucus, another key barrier for antibody transport. In vivo results in rats demonstrate that CGLY effectively delivers TNFα antibody into the intestinal mucosa as well as systemic circulation. One week repeat dose study followed by histology and serum biochemistry analysis indicates that CGLY is well tolerated by rats. Overall, this work illustrates the promise of using choline-based ionic liquids and deep eutectic solvents as an oral delivery platform for local as well as systemic delivery of therapeutic antibodies.