>> Research Projects >> Nanostructured Biomaterials

1. Modification of nanostructured biomaterials to optimize their biomedical applications.

Adaptation (or incorporation) of nanostructured materials into biomedical devices and systems has been of great interests in recent years.  Through the modification of existing nanostructured materials, one can control and tailor the properties of such materials in a predictable manner, and impart them with biological properties and functionality to better suit their integration with biomedical systems. These modified nanostructured materials can bring new and unique capability to a variety of biomedical applications ranging from implant engineering and modulated drug delivery, regenerative medicine,  to clinical biosensors and diagnostics.

One direction we are working on is to improve the bonding strength between nano-bioceramics and polymer matrix. Other’s data demonstrated that by mixing biodegradable polymer with nanophase bioceramics,  the mechanical  strength, biodegradability, osteoconductivity and osteoinductivity of the scaffold/implant can be improved significantly. However, a common problem with nanoceramic-polymer composites is the weak binding strength between the nanoceramic filler and the polymer matrix since they are two different categories of materials and cannot form covalent bonds between them during the mixing process. In most cases, the mechanical strength of the composites is compromised due to the phase separation of the nanoceramic filler from the polymer matrix. To overcome this problem, we activated nanoHA powder surfaces either by grafting functional groups (e.g., nanoHA-NH2 and nanoHA-COOH) or creating a biodegradable polymer coating at nanoscale thickness (Fig. 1). The treated nanoHA powders bind to the polymer matrix via covalent bonds and enhance the mechanical properties of the resultant composites.
 
Figure 1. High Resolution Transmission Electron Microscopy (HRTEM) images show the uncoated nanoHA (A), nanoHA with biodegradable coating (B), and nanoHA with nondegradable coating (C.).

The other direction is to modify the surface of nano-carbon tube arrays to improve their performances for biosensor application. 

2. Fabrication of nanostructured biomaterials for tissue regeneration.

We are also using nano-particles for the delivery of bioactive molecules. In one of our studies, prolyl hydroxylase inhibitors were loaded into degradable nanoparicles (Fig. 2) and were shown to suppress fibrous scar formation in skin and in brain tissue, and also promote angiogenesis. The rationale behind this study is that prolyl hydroxylases have long been understood to stabilize secreted collagen.   In our study, prolyl hydroxylase inhibitors (PHIs) were incorporated into degradable nano-carrier and used to activate the PHD-signaling pathway in a localized and controlled fashion in vivo.  Nanoparticles that incorporate PHIs induce a robust angiogenesis response subcutaneously and in brain tissue (Fig. 3).  In addition, less fibroses and collagen disposition was noted in the PHI-treated tissue.  The dual utility of these agents in both promoting angiogenesis and suppressing fibrosis suggest high potential in therapeutic uses.


Figure 2: PHI loaded biodegradable nanoparticles.

 
Figure 3. Blood vessels neighboring the nano-particle encapsulation delivery device at two weeks post-implantation. The number of blood vessel branches around the PHI delivering device (B) was significantly higher than that for blank control (A), suggesting that PHI promotes angiogenesis in CNS tissue. RECA-1 positive endothelial cells and blood vessels were stained in green. 

3. Fabrication of Loose Nanofiber Array for Tissue Regeneration.

It has been shown that nanofibers have many favorable characteristics as tissue engineering scaffolds.  Alignment of fibers in scaffolds allows directional guidance, which is an important characteristic when repairing tissues such as nerves, tendons, and muscles. Aligned nano-fibrous scaffolds can be fabricated by electrospinning onto a fast rotating mandrel. However, the as-fabricated scaffold is in a very dense matt form due to the adhesion between each individual fibers during the fabrication process.  The dense matt form of scaffold can only allow cells grow on the surface of the dense matt and greatly prevented cell penetrate inside the scaffold. If used for neural repair, for example, regenerating neurites can only grow on the surface and greatly limited the possible number of regenerating neurites in a confined volume.  Therefore, researchers are facing great difficulties in applying electrospun nanofibers for neural repair in vivo. To solve this problem, a novel method of fabricating loose 3-dimensional bundles of aligned nanofibers was developed in our lab and is evaluating in vitro and in vivo for nerve, tendon, ligament, and skeletal muscle regeneration.


Figure 4. 3-D array of aligned individual nanofibers.