Probing and Manipulating Noncovalent Interactions in Functional Polymeric Systems.

Noncovalent interactions, which usually feature tunable strength, reversibility, and environmental adaptability, have been recognized as driving forces in a variety of biological and chemical processes, contributing to the recognition between molecules, the formation of molecule clusters, and the establishment of complex structures of macromolecules. The marriage of noncovalent interactions and conventional covalent polymers offers the systems novel mechanical, physicochemical, and biological properties, which are highly dependent on the binding mechanisms of the noncovalent interactions that can be illuminated via quantification. This review systematically discusses the nanomechanical characterization of typical noncovalent interactions in polymeric systems, mainly through direct force measurements at microscopic, nanoscopic, and molecular levels, which provide quantitative information (e.g., ranges, strengths, and dynamics) on the binding behaviors. The fundamental understandings of intermolecular and interfacial interactions are then correlated to the macroscopic performances of a series of noncovalently bonded polymers, whose functions (e.g., stimuli-responsiveness, self-healing capacity, universal adhesiveness) can be customized through the manipulation of the noncovalent interactions, providing insights into the rational design of advanced materials with applications in biomedical, energy, environmental, and other engineering fields.

Injectable and Self-Healing Nanocomposite Hydrogels with Ultrasensitive pH-Responsiveness and Tunable Mechanical Properties: Implications for Controlled Drug Delivery.

Injectable, self-healing, and pH-responsive hydrogels are great intelligent drug delivery systems for controlled and localized therapeutic release. Hydrogels that show pH-sensitive behaviors in the mildly acidic range are ideal to be used for the treatment of regions showing local acidosis like tumors, wounds and infections. In this work, we present a facile preparation of an injectable, self-healing, and supersensitive pH-responsive nanocomposite hydrogel based on Schiff base reactions between aldehyde-functionalized polymers and amine-modified silica nanoparticles. The hydrogel shows fast gelation within 10 s, injectability, and rapid self-healing capability. Moreover, the hydrogel demonstrates excellent stability under neutral physiological conditions, while a sharp gel-sol transition is observed, induced by a faintly acidic environment, which is desirable for controlled drug delivery. The pH-responsiveness of the hydrogel is ultrasensitive, where the mechanical properties, hydrolytic degradation, and drug release behaviors can alter significantly when subjected to a slight pH change of 0.2. Additionally, the hydrogel's mechanical and pH-responsive properties can be readily tuned by its composition. Its excellent biocompatibility is confirmed by cytotoxicity tests toward human dermal fibroblast cells (HDFa). The novel injectable, self-healing, and sensitive pH-responsive hydrogel serves as a promising candidate as a localized drug carrier with controlled delivery capability, triggered by acidosis, holding great promise for cancer therapy, wound healing, and infection treatment.

A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing.

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.

Stretchable, compressible, and conductive hydrogel for sensitive wearable soft sensors.

Conductive hydrogels hold great promises in wearable soft electronics. However, the weak mechanical properties, low sensitivity and the absence of multifunctionalities (e.g., self-healing, self-adhesive, etc.) of the conventional conductive hydrogels limit their applications. Thus, developing multifunctional hydrogels may address some of these technical issues. In this work, a multifunctional conductive hydrogel strain sensor is fabricated by incorporating a conductive polymer Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) into a mechanically robust poly (vinyl alcohol) (PVA)/ poly (acrylic acid) (PAA) double network (DN) hydrogel. The as-prepared hydrogel sensor could span a wide spectrum of mechanical properties by simply tuning the polymer composition and the number of freezing-thawing cycles. In addition, the dynamic hydrogen bonding interactions endow the hydrogel sensor with self-healing property and reversible adhesiveness on diverse substrates. Moreover, the hydrogel sensor shows high sensitivity (Gauge Factor from 2.21 to 3.82) and can precisely detect some subtle human motions (e.g., pulse and vocal cord vibration). This work provides useful insights into the development of conductive hydrogel-based wearable soft electronics.

Coacervate-Based Instant and Repeatable Underwater Adhesive with Anticancer and Antibacterial Properties.

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.