Non-invasive Therapy for Soft Tissue Reconstruction: Applications in Cosmetics and Wound Healing

Soft tissue reconstruction is emerging as an important strategy to repair and replace diseased or damaged tissue that has been compromised due to tumour removal, injury, trauma, ageing, etc. It relies on two main approaches: (i) surgical autologous tissue displacement, or (ii) exogenous biomaterial implantation [1]. This project will focus on the latter.

The surgical approach suffers from donor site morbidity and surgical complications [2]. Unfortunately, this problem persists even with computer-assisted surgical reconstruction [3]. For instance, the complication rate among women who had postmastectomy breast reconstruction was 32.9% [4]. Importantly, surgical reconstruction is normally not considered for minor defects, for which exogenous biomaterial implantation is the preferred approach. However, biomaterial implantation is currently constrained by low volume retention and low local tissue regeneration rate. The biomaterials used are also mostly scaffolds made of synthetic materials and do not carry a drug payload.

In this project, we will instead use a peptide material to deliver a peptide drug, with a view to enhancing both volume retention and tissue regeneration rate. Peptides are highly diverse in their structures. They can self-assemble to form novel peptide hydrogels whose microenvironments mimic the extracellular matrix. Due to their outstanding safety profile, biocompatibility, and biodegradability, peptide hydrogels are an appealing drug delivery system, with important applications in cardiology, oncology, wound treatment, among others. The 3D network of the hydrogel will not only enable efficient colonisation and vascularisation of functional native soft tissue but will also protect the drug against enzymatic degradation.

In this project, we will synthesise: (A) A peptide-based hydrogel (B) A peptide-based drug. In designing the hydrogel (A), with the help of computational tools, we will select the predominant peptide sequence from the domain of selected protein. The cross-linking of the hydrogel will be investigated and optimised as it is directly correlated with the biodegradability, volume stability, and the drug release pattern. We anticipate the final hydrogel to sustain the release of the peptide drug over prolonged duration. We will probe the drug loading/release process through strategically positioned amino acids within the structures of the hydrogel and the drug, which will allow us to boost the volume retention of the final formula. The peptide drug (B) will be synthesised and loaded into the hydrogel (A); its loading capacity optimised accordingly. The drug (B) has demonstrated its ability (in vitro and in vivo) to boost extracellular matrix formation and significantly induce collagen, hyaluronic acid, and fibronectin production [5]. Since these molecules play significant roles in the tissue repair process, we anticipate the final formula to also enhance the local tissue regeneration process.

We will further investigate whether: (1) the dermal delivery of the drug can be enhanced with electroporating microneedles; (2) the peptide-based hydrogel can enhance the retention of the drug in the skin. These determinations are important to increase the bioavailability of the drug in the skin to promote collagen generation.

The drug formulation (hydrogel or solution) will be injected into ex vivo porcine skin. Drug permeation through the skin will be quantified. This will allow us to construct an in vitro biodistribution profile of the drug to compare the extent of drug retention and dermal clearance. The biocompatibility/immunogenicity of the formulation will be assessed in human immune cells.

The student will gain expertise in peptide synthesis, pharmaceutical formulation, chemical/pharmaceutical analysis, HPLC analysis, LCMS, purification, computational chemistry, tissue culture, biochemical assays and cellular assays for toxicological assessments.

Related publication:

Al Musaimi O, Ng KW, Gavva V, Mercado-Valenzo OM, Haroon HB, Williams DR. Elastin-Derived Peptide-Based Hydrogels as a Potential Drug Delivery System. Gels. 2024; 10(8):531. https://doi.org/10.3390/gels10080531