Nanotechnology for Application in Drug Delivery and Tissue Engineering
Research in the Xu Lab focuses on developing nanotechnologies for biomedical applications including nanomedicine and tissue engineering.
Lipid-based Nanoparticles for Delivery of Biomacromolecules
The utilization of biomacromolcules including proteins and nucleic acids as therapeutic drugs has gained huge interests in pharmaceutical industry. However, effective delivery of the biomacromolecular based drug to the desired organs remains challenge. The delivery nanoparticle must overcome many barriers in order to achieve therapeutic effects.
Our research aims to use chemical methods to synthesize non-viral lipid or polymer based nanocarriers to facilitate the intracellular delivery of biomacromolecules, including DNA, RNA and proteins for therapeutic applications. We are using combinatorial library strategy to generate lipid-based vectors, termed as “lipidoids”, and screening for their abilities to facilitate the cargo delivery in a high throughput manner. From the large data sets accumulated from screening the library of lipidoids, we aim to build a correlation between structure and function of delivery systems. Such knowledge will be useful for a rational design of novel delivery systems for molecular therapy with high efficiency and minimized toxicity.
Figure 1. (A) Transmission electron microscopic image of Lipid-DNA nanocomplex. (B) In vitro screening of library of lipidoids for DNA delivery in Hela cells.
Slicing and Dicing: Re-engineering Nature-Derived Materials for Tissue Engineering
Nature has evolved a variety of clever ways to create nanoscale entities with remarkable complexity. An enormous library of biological species has shown extremely well-defined shapes and chemical activity. For example, tendon comprises well-organized collagen nanofibers and striated skeletal muscle comprises well-aligned myofilaments. Other examples include cornea, bone, diatoms, and wood.
We aim to directly utilize the decellularized naturally derived tissue comprising well-organized micro- and nanostructures and re-engineer them using a combination of sectioning, stacking and rolling to form appropriate scaffold for tissue engineering. As proof-of-concept, we have created collagen-based constructs from decellularized tendon using a combination of sectioning, stacking and rolling. The unidirectionally aligned collagen nanofibers (derived from sections of decellularized tendon) could offer good mechanical properties to constructs, such as prosthetic grafts. Furthermore, the unidirectionally aligned collagen in tendon provides nanotopographic cues which can provide contact guidance for oriented cell growth. This capability is beneficial for tissue engineering applications where the biocompatibility and ability to guide unidirectional nerve growth are both desired.
Figure 2. A, B) Photograph of the 2D multilayered and 3D tubular constructs from tendon sections. (C) SEM image showing the bundles of well-aligned collagen nanofiber in the tendon section. (D) photograph of the tendon section seeded with smooth muscle cells (SMCs). (E) SMCs seeded tendon section wrapped around a rod template. (F) Fluorescent image showing the well-alignment of SMCs on the tendon section.
For more information see the Xu Page in Biomedical Engineering