The Experimental Therapy of Brain Injury by Tissue Engineering with Hyaluronic Acid Based Scaffold

Stroke causes death and severe disability highly and often result in cavity formation in the brain. The complexity of the CNS makes efforts to repair injuries very difficult. Tissue engineering in combination with stem cell transplantation has the potential to fill such a cavity and replace lost neurons. In our study, a three dimensional hyaluronic acid (HA) based hydrogel was created as a biodegradable tissue engineering scaffold to mimic the structure and components of the extracellular matrix (ECM) in the brain. The molecules of poly‐L‐lysine (PLL) were immobilized on the backbone of the hydrogel for improving cell adherence and compatibility with brain tissue. In addition, a pH sensitivity antibody releasing system was developed by covalently attaching the antibody of Nogo receptor (Ab‐NgR) to the hyaluronic acid (HA) hydrogel, delivering the antibody to the injured brain, which can bind to multiple inhibitory myelin proteins, such as Nogo‐66, and promote neural regeneration. The modified hydrogel would be suitable for the acidosis in the brain tissue after injury. The antibody delivery system or the modified hydrogel was shown to have strong action to induce the growth of axons from the dorsal root ganglia in vitro, in addition to helping the cell adherence and survival. After implanting to the adult rat model of ischemia with occlusion of the middle cerebral artery, this antibody delivery system showed to have promotion function with regard to regeneration of neural cells in the host brain and improvement of behavior in those ischemic models. After implantation of this polymer hydrogel into the injured area of the brain of rat models, it was clearly shown that the hydrogel had good compatibility with the brain tissue and inhibitory action for genesis of glial scar. Also, the hydrogel could correctly bridge the tissue defects and form a permissive interface with the host tissue to favour axonal ingrowth and angiogenesis. The HA hydrogel scaffolds modified by ab‐NgR and PLL are therefore appealing for cell delivery and tissue development in the brain following stroke.The work was supported by the National Natural Science Foundation of China (Grant Nos. 30700210, 30670656, 30570578), the National Basic Research Program of China (Grant No. 2007CB947704), and the Beijing Committee of Science and Technology (No. Z0005187040311).