Biomimetic hydrogels for tissue engineering

Although mesenchymal stem cells (MSC) serve as an attractive cell source for tissue engineering with their expansion potential and capacity for multilineage differentiation, their clinical use is predicated on finding ways to reliably differentiate them into desired phenotypes. To this end, we have employed cross-linked networks of synthetic hydrophilic polymers to form Michael addition hydrogels with a cell inductive  microenvironment. We have (1) employed signal peptides to promote chondrogenesis and MSC survival in polyethylene glycol hydrogels, (2) engineered self-assembled micelles to control cellular behavior, and (3) designed cationic polycarbonates as vehicles for gene delivery within the microenvironment. This research direction has potential applications in the fields of bone, cartilage and tendon engineering. 

A schematic diagram showing the synthesis of biodegradable nanostructured hydrogels with tunable physical properties for cell and gene delivery. The hydrogel was formed by reacting a four-arm acrylate-terminated PEG with a four-arm thiol-functionalized PEG.  Micellar structures incorporated into the hydrogel scaffold enhanced cell viability and gene expression of MSCs by providing a better environment for cell–matrix interactions. (Li et al., Biomaterials, 2012, 33, 6533-6541)

A collagen mimetic peptide​ was incorporated into the PEG Michael addition hydrogel and facilitated a desirable environment for chondrogenic differentiation of MSC into neocartilage, and may be useful for the repair of cartilage defects. (Liu et al., Biomaterials, 2010, 31, 7298-7307)

Synthetic peptides and polymers as novel antimicrobials

The rapid emergence of multidrug resistance coupled with a shrinking industrial pipeline of novel antibiotics have prompted the search for  alternative strategies in antimicrobial therapeutics. Our lab has adopted a systematic approach to fine-tune the clinical applicability of synthetic antimicrobial peptides (AMP) by studying how peptide secondary structures affect their antimicrobial activity and selectivity. We have established the relative importance of hydrophobicity, alpha-helical content, and amphiphilicity of AMP on its potency on a broad spectrum of microorganisms, including Mycobacterium tuberculosis.

Schematic illustration and helical wheel projection of α-helical AMP with idealized facial amphiphilicity. These AMP exhibited potent activity against bioluminescent Pseudomonas aeruginosa biofilms and suppressed LPS-induced pro-inflammatory mediators.  (Khara et al., Acta Biomaterialia, 2017, 15, 103-114)

We reported the encapsulation of amphotericin B into polymeric micelles self-assembled from polycarbonate/PEG (PEG-PBC) and urea-functionalized polycarbonate/PEG (PEG-PUC) diblock copolymers which were functionalized with phenylboronic acid. The micellar systems prolonged drug release with improved toxicity profiles compared to a commercial preparation.  (Wang et al., Acta Biomaterialia, 2016, 46, 211-220)