Enhanced Angiogenesis for Tissue Regeneration using Human Stem Cells and Biodegradable Nanoparticulate Polymeric Vectors

摘要

Mesenchymal stem cells (MSC) are progenitor cells which can differentiate down multiple lineages including bone. Ideally, scaffold for bone tissue engineering should exhibit biofunctionality of natural materials. In this regards, a novel polymeric biocomposite hydrogel was synthesized by covalently binding of polyethylene glycol (PEG). The most common injuries in battle fields are amputated limbs and massive loss of craniofacial tissues. Current therapies for traumatic tissue injury utilize non-biological and non- degradable materials, which could not provide satisfactory long-term biological function recovery. Angiogenesis is a crucial step for tissue regeneration and integration with the host tissue for function recovery. Vascular endothelial growth factor (VEGF) is a positive regulator and plays a crucial role in angiogenesis. Stem cells have received significant attention as the next generation therapeutics for regenerative medicine. Using stem cells as delivery vehicles for VEGF holds great promise to enhance angiogenesis and tissue regeneration. The major barrier to gene delivery to stem cells is the lack of safe and efficient DNA delivery methods. Viral methods are high efficient in transferring DNA to the stem cells, but are limited by potential toxicity and immunogenicity. Non-viral systems can circumvent these problems but suffer from low transfection efficiency. Our lab developed a large library of 2350 structurally unique poly(Beta-amino esters) using combinatorial chemistry. High-throughput screening has shown PBAEs that are promising for non-viral gene delivery due to their ability to condense DNA into small size nanoparticles, low cytotoxicity, and biodegradability.