Injectable cell hydrogel composites for articular cartilage tissue engineering
Mikos, Antonios G.
Doctor of Philosophy
Due to their invasiveness as well as the complex properties of articular cartilage current treatments often fail to restore cartilage damage. Thus, tissue engineering approaches have received attention as a promising alternative to treat cartilage disease. A variety of natural and synthetic materials have been developed as potential carriers for cells or therapeutic agents for cartilage repair. In particular, injectable and biodegradable materials hold promise for cartilage tissue engineering due to the ease of administration and their biomimetic properties. In this thesis, an injectable hydrogel based on oligo(poly(ethylene glycol)) in conjunction with cells and gelatin microparticles loaded with growth factors is examined. First, bovine chondrocytes were encapsulated in hydrogel composites based on the biodegradable polymer, oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (MP) loaded with transforming growth factor-beta1 (TGF-beta1). The results demonstrated that the presence of loaded gelatin microparticles promoted cell proliferation while maintaining a chondrocytic phenotype. A following study investigated OPF hydrogel composites encapsulating gelatin microparticles as the delivery vehicle for rabbit marrow mesenchymal stem cells (MSCs). Gene expression results showed that chondrocyte-specific gene expression of type II collagen and aggrecan were only evident in groups containing TGF-beta1-loaded MPs and varied with TGF-beta1 concentration in a dose dependent manner. OPF with two different repeating units (PEG 10K and PEG 3K) were then prepared for encapsulation of rabbit MSCs and TGF-beta1-loaded MPs to examine the effect of swelling ratio on chondrogenic differentiation of encapsulated rabbit MSCs both with and without TGF-beta1. The result demonstrated OPF hydrogel composites with the higher swelling ratio resulted in the higher level of chondrocyte-specific gene expressions. Finally, OPF hydrogel composites were evaluated as the delivery matrix for dual growth factors (TGF-beta1 and IGF-1) for in vitro chondrogenic differentiation of encapsulated MSCs. The presence of IGF-1-loaded MPs promoted the aggregation of rabbit MSCs encapsulated in hydrogels. Additionally, rabbit MSCs had the upregulation of the chondrocyte-specific genes such as collagen type II and aggrecan only in the presence of TGF-beta1-loaded MPs.