In the medical field, one area that has always been of interest is how drugs and medical therapeutics can be better delivered to the human body. Over the last several decades, scientists have been looking at hydrogels as a means of drug delivery.
Application of hydrogels
Hydrogels are three-dimensional materials made of hydrophilic networks – or water-soluble – polymers. They have been used in a variety of products and roles, from cosmetics and diapers, to contact lenses and wound dressings, due to their ability to swell and hold a large amount of water. Scientists are particularly interested in the application of hydrogels for the delivery of drugs to human tissue.
Supramolecular hydrogels made from peptides were seen as a promising path for drug delivery, but existing long peptide gelators have drawbacks that hinder their practical applications: these long peptide sequences require more time to synthesize, have weaker mechanical properties, and it is challenging to get them to encapsulate precise amounts of therapeutics in a timely manner. Long peptide sequences can also sometimes elicit undesired immunogenic responses. Some peptide hydrogels require a complex cross-linking process to gelate, in which chemical additives or UV irradiation are needed. This can lead to denaturation and degradation of sensitive therapeutic products encapsulated, such as growth factors (proteins). These issues have proved a significant obstacle to the advancement of their use in the medical field.
However, a recent breakthrough by a team of scientists, jointly led by Asst Prof Dalton Tay Chor Yong and Prof Ali Miserez from NTU’s School of Biological Sciences and School of Materials Science and Engineering and Dr Hiew Shu Hui, a senior Research Fellow in Prof Miserez’s lab, has demonstrated that a short octapeptide inspired by biological structures, can circumvent the issues faced by peptide hydrogels and successfully encapsulate and deliver protein therapeutics.
Left to right: Asst Prof Tay Chor Yong, Prof Ali Miserez and Dr Hiew Shu Hui
Squid proteins for a better hydrogel
Developed from a protein found in the Humboldt squid sucker-ring teeth, the short peptide Ac-GLYGGYGV-NH2 (GV8), can self-assemble into a supramolecular hydrogel with a multitude of advantageous characteristics that make it highly favourable for drug delivery and wound healing applications. It has a simple one-pot encapsulation and gelation procedure, which helps preserve the functions of encapsulated therapeutics. The system also enables controllable drug loading and release, with tuneable hydrogel mechanical properties.
Sucker ring teeth of the humboldt squid
The encapsulation and delivery of protein-based therapeutics can be complicated and challenging as proteins are highly sensitive to their environment and susceptible to denaturation and degradation. This is where the GV8 hydrogel comes in handy: It can self-assemble under mild aqueous conditions over a wide pH range of 3.5 to 7.5, at ambient temperatures of 23- 25 ⁰C. The gelation process also does not require cross-linking via the addition of chemicals or UV irradiation. Therefore, GV8 hydrogels can easily incorporate protein therapeutics and preserve their structures, hence maintaining the therapeutics’ functionality and healing efficacy.
GV8 hydrogels also have physico-chemical properties that can be controlled by adjusting peptide concentrations, such as shear storage modulus and network porosity. This allows for the fine-tuning of drug release rates, allowing controlled release of drugs to be delivered to tissues over a stipulated period rather than burst release.
Dr Hiew and Asst Prof Tay in action in the lab
With these advantages of GV8 hydrogel, the team from NTU loaded the GV8 hydrogels with growth factors (GFs) and adipose-derived mesenchymal stem cells (ADMSC) secretome. The loaded hydrogels, termed GV8+, were able to deliver the encapsulated therapeutics, all while maintaining their activities. GV8+ promoted accelerated wound closure and the development of new blood vessels, ensuring a rapid healing process.
In this petri dish: a tube of hydrogel, a drop of hydrogel and humboldt squid sucker ring teeth
The future of hydrogels
The team from NTU has shown that the use of GV8 short peptide hydrogels can overcome the challenges currently faced by existing peptide hydrogels, particularly those with longer peptide sequences. GV8 hydrogel is a versatile system and will be a game-changing in the field of regenerative medicine, harnessing GFs and ADMSC secretome for wound healing. As of now, more studies will have to be done on GV8 before it can be further applied in medicine, such as future work looking at the effective dose responses for the ADMSC secretome-loaded GV8+ system.