Joey Hui Min Wong’s research while affiliated with Agency for Science, Technology and Research (A*STAR) and other places

Given their hydrophilic nature, hydrogels have shown great potential as wound dressing materials. However, traditional hydrogel dressing materials are static and do not adapt to dynamic wound environments, which in turn limits their wound healing efficacy. Introducing dynamic covalent chemistries can be an effective strategy to improve hydrogel properties for effective wound healing, such as shape adaptability, stimuli responsiveness, self-healing capability, and antibacterial properties. We discuss the properties and chemistries of dynamic covalent bonds for wound healing. We critically analyze the advances of dynamic covalent hydrogels for wound healing and further propose new dynamic covalent chemistries for wound healing.

Nanotechnology has emerged as a highly promising platform for theranostics, offering dual capabilities in targeted imaging and therapy. Interactions between the nanomaterial and biological components determine the in vivo fate of these materials which makes the control of their surface properties of utmost importance. Nanoparticles with neutral or negative surface charge have a longer circulation time while positively charged nanoparticles have higher affinity to cells and better cellular uptake. This trade-off presents a key challenge in optimizing surface charge for theranostic applications. A sophisticated solution is an on-demand switch of surface charge, enabled by leveraging the distinct pH conditions at the target site. In this review, we explore the intricate relationship between pH and charge modulation, summarizing recent advances in pH-induced charge-switchable nanomaterials for theranostics over the past five years. Additionally, we discuss how these innovations enhance targeted drug delivery and imaging contrast and provide perspectives on future directions for this transformative field.

Diabetic ocular complications continue to be the leading cause of vision impairment in the world, with a considerable impact to healthcare and the global economy. While there are management strategies currently in place to delay the progression of diabetic ocular disease, risks associated with those strategies still pose a major concern in the clinical field. Management strategies generally involve ocular drug administration and surgical intervention. Some limitations with current ocular drug delivery systems include poor bioavailability of drug formulations and complications arising from drug regimens that require frequent intravitreal injections for drug administration. A vitrectomy is also a common surgical procedure to replace severely damaged vitreous caused by various diabetic ocular complications. However, existing vitreous substitutes used for post-vitrectomy surgery have a certain degree of toxicity to ocular tissues. Thermogels are well-suited materials for the treatment of diabetic ocular diseases as they could mimic the properties of ocular tissues to maintain the viability of therapeutics, serve as drug delivery depots and be tailored to be mechanically robust and non-toxic. Furthermore, the thermoresponsive property of thermogels imparts in situ gelling properties to create injectable mediums for minimally invasive disease management strategies. This review covers some of the latest developments in the field, highlighting the advantages of thermogels as sustained drug delivery systems, biocompatible and non-toxic vitreous substitutes, shape conformable implants and long-acting therapeutics over conventional treatments used for the treatment of diabetic ocular diseases.

Hydrogels with more than one mode of crosslinking have gained interest due to improved control over hydrogel properties such as mechanical strength using multiple stimuli. In this work, sodium alginate was covalently conjugated onto thermoresponsive polyurethanes to prepare hybrid polymers (EPC-Alg) that are responsive to both temperature and Ca²⁺, forming orthogonally crosslinked hydrogels which are non-toxic to cells. Notably, the crosslinks are fully reversible, allowing for gel strength to be modulated via selective removal of either stimulus, or complete deconstruction of the hydrogel network by removing both stimuli. Higher alginate fractions increased the hydrophilicity and Ca²⁺ response of the EPC-Alg hydrogel, enabling tunable modulation of the thermal stability, stiffness and gelation temperatures. The EPC-Alg hydrogel could sustain protein release for a month and encapsulate neural spheroids with high cell viability after 7-day culture, demonstrating feasibility towards 3D cell encapsulation in cell-based biomedical applications such as cell encapsulation and cell therapy.

Hydrogels are a promising drug delivery system for biomedical applications due to its 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.