Hydrogel for light delivery in biomedical applications.

Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.

Electrically Conductive Polymers for Additive Manufacturing.

The use of electrically conductive polymers (CPs) in the development of electronic devices has attracted significant interest due to their unique intrinsic properties, which result from the synergistic combination of physicochemical properties in conventional polymers with the electronic properties of metals or semiconductors. Most conventional methods adopted for the fabrication of devices with nonplanar morphologies are still challenged by the poor ionic/electronic mobility of end products. Additive manufacturing (AM) brings about exciting prospects to the realm of CPs by enabling greater design freedom, more elaborate structures, quicker prototyping, relatively low cost, and more environmentally friendly electronic device creation. A growing variety of AM technologies are becoming available for three-dimensional (3D) printing of conductive devices, i.e., vat photopolymerization (VP), material extrusion (ME), powder bed fusion (PBF), material jetting (MJ), and lamination object manufacturing (LOM). In this review, we provide an overview of the recent research progress in the area of CPs developed for AM, which advances the design and development of future electronic devices. We consider different AM techniques, vis-à-vis, their development progress and respective challenges in printing CPs. We also discuss the material requirements and notable advances in 3D printing of CPs, as well as their potential electronic applications including wearable electronics, sensors, energy storage and conversion devices, etc. This review concludes with an outlook on AM of CPs.

Towards machine learning for hydrogel drug delivery systems.

Hydrogel drug delivery system development is complex and laborious, and machine learning (ML) techniques hold great promise in accelerating the process. We highlight recent advances and strategies for data collection and ML, and we discuss the potential for and barriers to the broader use of ML for hydrogel drug delivery systems.

Bottom-up design of hydrogels for programmable drug release.

Hydrogels are a promising drug delivery system for biomedical applications due to their biocompatibility and similarity to native tissue. Programming the release rate from hydrogels is critical to ensure release of desired dosage over specified durations, particularly with the advent of more complicated medical regimens such as combinatorial drug therapy. While it is known how hydrogel structure affects release, the parameters that can be explicitly controlled to modulate release ab initio could be useful for hydrogel design. In this review, we first survey common physical models of hydrogel release. We then extensively go through the various input parameters that we can exercise direct control over, at the levels of synthesis, formulation, fabrication and environment. We also illustrate some examples where hydrogels can be programmed with the input parameters for temporally and spatially defined release. Finally, we discuss the exciting potential and challenges for programming release, and potential implications with the advent of machine learning.

Cationic Lignin-Based Hyperbranched Polymers to Circumvent Drug Resistance in Pseudomonas Keratitis.

The rise of antimicrobial-resistant bacteria strains has been a global public health concern due to their ability to cause increased patient morbidity and a greater burden on the healthcare system. As one of the potential solutions to overcome such bacterial infections, hyperbranched copolymers with cationic charges were developed. These copolymers were assessed for their antimicrobial efficacy and their bactericidal mechanisms. They were found to be potent against mobile colistin-resistant 1 strains, which was significant as colistin is known to be the last-resort antibiotic against Gram-negative bacteria. Furthermore, there was no sign of mutational resistance developed by E. ColiATCC 25922 and MCR 1+E. Coli against the copolymer even up to 20 passages. The ability to evade inducing resistance would provide invaluable insights for future antibiotic development. Our studies suggest that the bactericidal efficacy comes from the ability to target the outer membrane efficaciously. In vivo study using a Pseudomonas keratitis model showed that the copolymer was compatible with the eye and further supported that the copolymer treatment was effective for complete bacteria elimination.

A New Potent Antimicrobial Metalloporphyrin.

A series of bis-acryl functionalized porphyrins and their corresponding metalloporphyrins (M=Co, Mn) were synthesized and investigated for their antimicrobial properties through MIC screening and bacteria time-kill kinetic studies. The Mn(III) 4-(bis)methylphenyl-substituted-porphyrins showed superior batericidal activities even in the dark with low hemotoxicity and good cytotoxicity profile.

Gold-decorated TiO2 nanofibrous hybrid for improved solar-driven photocatalytic pollutant degradation.

TiO2-based nanomaterials are among the most promising photocatalysts for degrading organic dye pollutants. In this work, Au-TiO2 nanofibers were fabricated by the electrospinning technique, followed by calcination in air at 500 °C. Morphological and structural analyses revealed that the composite consists of TiO2 nanofibers with embedded Au nanoparticles that are extensively distributed throughout the porous fibrous structure of TiO2. The photocatalytic performance of these Au-embedded TiO2 nanofibers was evaluated in the photodegradation of Rhodamine B and methylene blue under solar simulator irradiation. Compared with pristine TiO2 nanofibers, the Au-embedded TiO2 nanofibers displayed far better photocatalytic degradation efficiency. The plasmon resonance absorption of Au nanoparticles in the visible spectral region and the effective charge separation at the heterojunction of the Au-TiO2 hybrid are the key factors that have led to the considerable enhancement of the photocatalytic activity. The results of this study clearly demonstrate the potential of Au-TiO2 electrospun nanofibers as solar-light-responsive photocatalysts for the effective removal of dye contaminants from aquatic environments.

Engineering luminescent pectin-based hydrogel for highly efficient multiple sensing.

Luminescent hydrogels with sensing capabilities have attracted much interest in recent years, especially those responsive to stimuli, making such materials potential for various applications. Pectin is a high-molecular-weight carbohydrate polymer that has the ability to form hydrogel upon heating or mixing with divalent cations. However, intrinsic pectin gels are weak and lack of functionalities. In this study, lanthanide ions and silk fibroin derived carbon dots were incorporated into Pectin/PVA hydrogel (PPH) to form luminescent tough hydrogels. The luminescence of the hydrogel can be tuned by adjusting the ratio of blue emission carbon dots to Eu3+ ions (red emission) and Tb3+ ions (green emission). Such incorporation of emitters only slightly changed the mechanical properties of the tough hydrogel. Notably, the luminescent Pectin/PVA hydrogel (LPPH) showed chromic response to external stimuli, like pH and metal ions. By measuring the ratio of luminescent intensity at 473 nm and 617 nm (I473/I617), the pH response can be quantified in high sensitivity. In addition, the specific detection of Cu2+ and Fe3+ ions using the fabricated hydrogel were demonstrated, the mechanism was also proposed. The different chromic responses to Fe2+ and Fe3+ endow the luminescent tough Pectin/PVA hydrogel potential for multiple sensing applications.

Sanitizing agents for virus inactivation and disinfection.

Viral epidemics develop from the emergence of new variants of infectious viruses. The lack of effective antiviral treatments for the new viral infections coupled with rapid community spread of the infection often result in major human and financial loss. Viral transmissions can occur via close human-to-human contact or via contacting a contaminated surface. Thus, careful disinfection or sanitization is essential to curtail viral spread. A myriad of disinfectants/sanitizing agents/biocidal agents are available that can inactivate viruses, but their effectiveness is dependent upon many factors such as concentration of agent, reaction time, temperature, and organic load. In this work, we review common commercially available disinfectants agents available on the market and evaluate their effectiveness under various application conditions. In addition, this work also seeks to debunk common myths about viral inactivation and highlight new exciting advances in the development of potential sanitizing agents.

Tough hydrogel module towards an implantable remote and controlled release device.

On-demand controllable drug delivery systems enable the administration of precise dosages and thus have the potential to improve overall healthcare. In this work, a tough physical hydrogel is developed and studied for triggered burst release. Semicrystalline poly (vinyl alcohol) (PVA) is combined with ionic pectin (CaP) to form an interpenetrating network (PVA-CaP). The synergistic combination of crosslinking mechanisms resulted in a threefold improvement in tensile modulus and fracture energy over pristine PVA. As a result of the physical network, crosslink dissociation could be induced by heating. This trait is used as a trigger for burst release of a payload in PVA-CaP flexible substrates. Highly localized and on-demand burst release can be effectively achieved through the inclusion of electronic devices. Cell adhesion and viability tests show that the addition of pectin remarkably improves cell attachment ability and provides a favourable environment for cell proliferation. Implantation tests finally show the suitability of the material for implantation and its ability to conform with natural tissue. Such a system is envisioned for use as an implantable remote and controlled release device.

Recent innovations in artificial skin.

The skin is a "smart", multifunctional organ that is protective, self-healing and capable of sensing and many forms of artificial skins have been developed with properties and functionalities approximating those of natural skin. Starting from specific commercial products for the treatment of burns, progress in two fields of research has since allowed these remarkable materials to be viable skin replacements for a wide range of dermatological conditions. This review maps out the development of bioengineered skin replacements and synthetic skin substitutes, including electronic skins. The specific behaviors of these skins are highlighted, and the performances of both types of artificial skins are evaluated against this. Moving beyond mere replication, highly advanced artificial skin materials are also identified as potential augmented skins that can be used as flexible electronics for health-care monitoring and other applications.

Cationic Poly([R]-3-hydroxybutyrate) Copolymers as Antimicrobial Agents.

Poly([R]-3-hydroxybutyrate) (PHB), a natural biodegradable polyester, has attracted much attention as a new biomaterial because of its sustainability and good biocompatibility. In this study, it is discovered that PHB can be conveniently functionalized to obtain a number of platform chain architectures that may provide a wide range of functional copolymers. In a transesterification reaction, linear (di-hydroxylated) and star shaped (tri- and tetra-hydroxylated) PHB oligomers are synthesized, followed by copolymerization with 2-(dimethylamino)ethyl methacrylate and quaternization with benzyl bromide to afford antimicrobial properties. The antimicrobial activities of the quaternary salts against clinically relevant pathogens on the interactions with outer and cytoplasmic membranes, lethal mechanisms, multipassage resistance, and synergy effect with antibiotics are investigated. Cationic PHB copolymers show effectiveness as antimicrobial agents, with minimum inhibitory concentration values 0.24-0.65 µm (or µmol dm-3 ) (or 32-128 µg mL-1 ) against Gram-positive and Gram-negative bacteria. Modifying the copolymer architectures into star shapes results in enhanced effectiveness to disrupt the membrane integrity. Synergistic effects are attained for all the quaternized PHB derivatives when they are used together with tobramycin. Multipassage resistance does not occur in both the linear and star derivatives against Gram-negative bacteria after 20 passages.

Using Artificial Skin Devices as Skin Replacements: Insights into Superficial Treatment.

Artificial skin devices are able to mimic the flexibility and sensory perception abilities of the skin. They have thus garnered attention in the biomedical field as potential skin replacements. This Review delves into issues pertaining to these skin-deep devices. It first elaborates on the roles that these devices have to fulfill as skin replacements, and identify strategies that are used to achieve such functionality. Following which, a comparison is done between the current state of these skin-deep devices and that of natural skin. Finally, an outlook on artificial skin devices is presented, which discusses how complementary technologies can create skin enhancements, and what challenges face such devices.

Supramolecular hydrogels for antimicrobial therapy.

The emergence of drug-resistant microbes has become a threat to global health, and microbial infections severely limit the use of healthcare materials. To achieve efficient antimicrobial therapy, supramolecular hydrogels demonstrate unprecedented advantages in medical applications due to the tunable and reversible nature of their supramolecular interactions and the capability of hydrogels to incorporate various therapeutic agents. Herein, antimicrobial hydrogels are categorized according to their inherent antimicrobial properties or based on their roles in encapsulating antimicrobial materials. Moreover, strategies to further enhance the antimicrobial efficacy of hydrogels are highlighted, such as the incorporation of antifouling agents or the enabling of response towards physiological cues. We envision that supramolecular hydrogels, in combination with modern medical technology and devices, will contribute to the development of efficient and safe systems for antimicrobial therapy.

Unexpected formation of gold nanoflowers by a green synthesis method as agents for a safe and effective photothermal therapy.

Star fruit (Averrhoa carambola) juice rich in vitamin C and polyphenolic antioxidants was used to synthesize branched gold nanoflowers. These biocompatible and stable gold nanoflowers show strong near-infrared absorption. They are successfully demonstrated to be highly efficient for both in vitro and in vivo photothermal therapy by using an 808 nm laser.

Codelivery for Paclitaxel and Bcl-2 Conversion Gene by PHB-PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy.

Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells.

Bioimaging and biodetection assisted with TTA-UC materials.

Upconversion of light has attracted intensive studies for biomedical research, because it enables deeper tissue analysis owing to the longer wavelength of incident light, compared with conventional downconversion fluorescent materials. Triplet-triplet annihilation (TTA), as a typical mechanism of upconversion, does not necessitate high power excitation and exhibits a higher quantum yield than rare earth upconversion owing to more sensitizer options with higher absorption coefficients. A desirable wavelength range of excitation and emission can be realized by careful selection of the combination of sensitizer and activator. Therefore, TTA-UC is worth exploring further for biorelated applications, such as bioimaging and biodetection. Recent developments are reviewed in this article.

Supramolecular cyclodextrin nanocarriers for chemo- and gene therapy towards the effective treatment of drug resistant cancers.

A tumor active targeting ß-cyclodextrin based nanocarrier ß-NC-OEI-SS-FA was designed by the modification of star shaped cationic derivatives ß-NC-OEI with folic acid through a disulfide bond, to co-deliver chemotherapeutic paclitaxel and the Nur77 gene for overcoming Bcl-2 mediated non-pump resistance by an "enemy to friend" strategy for potential drug resistant cancer therapy.

Recent Advances in Shape Memory Soft Materials for Biomedical Applications.

Shape memory polymers (SMPs) are smart and adaptive materials able to recover their shape through an external stimulus. This functionality, combined with the good biocompatibility of polymers, has garnered much interest for biomedical applications. In this review, we discuss the design considerations critical to the successful integration of SMPs for use in vivo. We also highlight recent work on three classes of SMPs: shape memory polymers and blends, shape memory polymer composites, and shape memory hydrogels. These developments open the possibility of incorporating SMPs into device design, which can lead to vast technological improvements in the biomedical field.

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix.

We have developed a "self-healing" polyglycerol sebacate-polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/α-Cyclodextrin (αCD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly "heal" itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use in vivo. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of αCD) between a fraction of a kPa to a few 100 kPa, a range that coincides with the moduli of cells and human soft tissues. This property would allow for this hydrogel to be used in vivo with maximal mechanical compatibility with human soft tissues. In vitro experiments showed that the hydrogel demonstrated a linear mass erosion profile and a biphasic drug (doxorubicin) release profile: Phase I was primarily driven by diffusion and Phase II was driven by hydrogel erosion. The diffusion mechanism was modeled with the First Order equation and the erosion mechanism with the Hopfenberg equation. This established fitting model could be used to predict releases with other drugs and estimate the composition of the hydrogel required to achieve a desired release rate.