Principal Investigator

RECEIVED NJ COMMISSION ON SPINAL CORD RESEARCH As stated in the proposal, the broad, long-term objective of this research is to develop a force-actuating, implantable biomaterial to spur regeneration and growth of the spinal cord. Two general tissue engineering strategies have been employed in attempt to restore spinal cord function following trauma. The first and most prevalent is the development of biomaterials that serve as bioactive scaffolds to stimulate neurites to regenerate and grow through the injury site. The second strategy is to employ mechanical force, or traction, to axons at very slow rates and physically force the nerves to grow. The second technique has been used in vitro to generate neural tissue in the hope of ultimately "splicing" together the spinal cord. Specific Aim 1: To identify the force-actuating potential of DNA-crosslinked hydrogels. Hypothesis: Increasing the stiffness of the hydrogel by introducing more crosslinks will cause the hydrogel to shrink and exert force. Specific Aim 3: To determine the potential for the functionalized, force-actuating gels to control axon growth in vitro. We were granted one year of funding, beginning December 15, 2004. Therefore, two of the three stated specific aims were accomplished. Force-actuating potential of DNA-crosslinked hydrogels A special chamber of 20x5x5 mm was designed to perform the force actuation experiment. A porous polymer block was rigidly glued to one end of the chamber and another porous block was placed at the other end. A calibrated force transducer was glued to the free block. Sufficient room was provided in the chamber for the hydrogel to swell as shown in figure 1. Two designs of the DNA crosslinked hydrogel are considered, 01 and 03, with base lengths of 20:20:40 and 10: 10:20 for SA 1, SA2 and L2 crosslinker respectively. It was observed in a previous study that gelation at room temperature occurs at 50% crosslink for design 01 and at 30% crosslink for the design 03. This is used as a starting point and a 50% crosslinked 01 gel is cast inside the chamber. The gel gets interlaced in the porous polymer, thus attaching rigidly after gelation. 1X TE buffer is introduced in the chamber, until the gel is completely immersed, to swell the gel to equilibrium. After 2 hours of swelling, the TE buffer is drained out leaving just enough for keeping the gel hydrated. For the 03 gel, a 30% gel is cast in the chamber and …