The Study Of Hyaluronic Acid Based Scanffold For Central Nervous System Tissue Engineering

The regeneration of central nervous system (CNS) is world wide puzzle.Compared with skin, muscle, liver and peripheral nervous system, CNS haslimited ability to restore itself. Tissue engineering is one of promisingstrategies to promote the regeneration of CNS. By mimicing the structure andcomponents of the extracellular matrix (ECM) of the central nervous system,hyaluronic acid based hydrogel was studied as the tissue engineering scaffoldfor CNS. Because previous work showed that pure HA was ineffective assubstrate for nerve fiber growth because of a lack of cell adherence, lamininand poly-d-lysine (PDL) were immobilized on the backbone of the hydrogels.The in vitro cell culture study showed that 3D hydrogel could promote celladhesion and to support cell growth and to retain the differentiated function.After implantation into the injure brain of rat model, the polymer hydrogelcould correctly bridge the tissue defects, form a permissive interface with thehost tissue to favour cell ingrowth and angisgenesis.A new antibody (IgG) releasing system has been developed by covalently attachingIgG to the biodegradable hyaluronic acid (HA) hydrogel via the hydrolyticallyunstable hydrazone linkage, aiming to deliver the antibody of CNS regenerationinhibitors to the injured brain. Furthermore, pH sensitive linkage-hydrozone has beenformed between hydrogel and antibody. At low pH, the antibodies released quite fast.However, the antibodies released much slower in neutral and alkaline environment.Clinical and laboratory investigations have suggested that traumatic brain injury canproduce metabolic acidosis and reductions in cellular pH. Acidosis of the brain istypically transient, the pH recovers to physiological levels in hours. Therefore, releaserate of the antibody in this delivery system can be regulated with the changing pH oftraumatic brain tissue environment.The antibody delivery system administered to neuron cell adherence andsurvival. Furthermore it could release antibody and induce neurite outgrowth invitro. After implanting to the adult rat model of middle cerebral arteryocclusion, the antibody delivery system promoted the regeneration andimproved functional recovery dramatically in adult rat model. The β-tublin-Шpositive neurons were found in the hydrogel implanted into the brain.