Access Type

Open Access Dissertation

Date of Award

1-1-2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Weiping Ren

Abstract

Orthopedic implants might not directly unite with bones especially in compromised patients even if they have been appropriately fixed. The lack of early osseointegration would lead to the failure of the orthopedic implant. A “bone-like” implant surface is urgently needed to accelerate osseointegration. Electrospun nanofiber (NF) is a promising implant coating due to its highly porous nanoscale structure. It mimics the collagen I nanofibrous network of bone tissue; meanwhile it has been widely used as a drug delivery device. However, its compact and dense structure is not ideal for cell growth. Our strategy was to develop a functional three-dimensional (3D) NF implant coating to enhance osseointegration. Firstly, based on a coronal discharge effect 3D polycaprolactone (PCL) NF-zero, -low, -mid, and –high were fabricated by a self- developed automatic 3D NF collector with different collector movement speeds. Simply, the properties of the 3D PCL NFs were altered by the different speeds of the collector movement. The thickness, pore sizes/volumes, porosity and surface roughness of NFs were proportional to the moving speeds; and the fiber stiffness was increased by a faster movement due to higher fiber crystallinity. Cells should be very sensitive to the changes of living environments. With the aim to investigate how cells choose their preferred environments and to define the optimal NFs for drug release, we cultured pre-osteoblast MC3T3-E1 cells, pre- osteoclast RAW cells and rat adipose derive stem cells (ASCs) on the four types of NFs and studied the proliferation, distribution and differentiation of these cells. The looser structure, higher surface roughness and stiffness of the NF-high enhanced the proliferation and distribution of preosteoblasts and ASCs. Additionally, they had a positive effect on the differentiation of pre-osteoblast cells. Interestingly, the RAW cells preferred the dense NFs and had a higher proliferation. Combining the results above, we chose NF-high as the optimal NF for the drug delivery device study. Finally, we imported PLGA to the previously developed PCL/PVA coaxial system to accelerate degradation and developed strontium doped coaxial 3D PCL/PLGA (1:1)-PVA nanofibers. The coaxial NFs enabled the control of strontium release. The Sr2+ was released from the coaxial NFs over 2 months and the concentration was relatively constant. The released Sr2+ had a positive effect on the proliferation and differentiation of preosteoblast cells in both indirect cell contact and direct cell contact studies. We believe these coaxial NFs have a great potential as implant coatings. We will test the osseointegration efficiency of NF coated Titanium implants in a rat tibia defect model in the future.

Comments

This is a revised thesis, submitted with permission from the Graduate School of Wayne State.

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