Silver Nanoparticles As Drug Delivery Systems

Abstract

The goal of this project is to study the potential applications of silver nanoparticles (SNPs) in the medical device and pharmaceutical industries. Bone cements have been used in the orthopedic surgeries for many years to anchor prosthetics while filling up the spaces between the prostheses and bone. Antibiotics are an active component of bone cements but the increasing bacterial resistance to these antibiotics and difficulty of shaping and molding the bone cements increases the need for new antimicrobial biomaterials. Adult stem cell based regenerative therapies have been one of the most widely researched areas of tissue engineering. This is due to the recent success of in vitro differentiation of stem cells and a high demand to replace damaged organs and tissues from autologous and allogenic source using regenerative methods. In bone regeneration, growth fact based surgeries have lead to the calcification bones outside the surgical site. Here, we test a SNP based osteogenic drug delivery system, both in vitro and in vivo, that will provide clinicians and health care providers control of the activation stem cell differentiation leading to the formation of bone. We will evaluate the in vitro osteogenic differentiation of human adipose stem cells with light mediated miR-148b-Nanoparticle conjugates. We will functionalize SNPs with osteogenic miR-14b with a UV sensitive photocleavble group and a TAMRA 563 molecule. The SNP-miR-148b conjugates will be added to hASCs and activated with UV radiation that will release the miR-148 from the conjugate. The released miRNA will differentiation stem cells into osteoblast. The upregulation of early and late stage osteogenic differentiation markers like ALPL, OCN and Runx2 will be analyzed by qRT-PCR and histological stains (ALPL stain and Alizarin Red). Also, we will evaluate the healing of critical size mouse calvarial defects with light activated miR-148b-Nanoparticle conjugates. After testing the in vitro differentiation of hASCs, we will evaluate the healing of calvarial size defects with SNP-miR-148b. A 4 mm critical size defect (non-healing) will be drilled on the skull of mice and filled with non-osteogenic Polycaprolactone (PCL) scaffolds. Prior to implantation, the scaffolds will be seeded with hASCs, transfected with SNP-miR-148b conjugates and radiated with UV. The healing of the defect will be analyzed with micro-CT and histological staining after 4 and 12 weeks post implantation.