The Preparation Of Injectable Composite Hydrogel With Microsphere Used As Cartilage Bionic Scaffold

In cartilage tissue engineering, the adapt environment which cartilage cells or tissue rely on is applied by biomedical scaffolds. The hydrogels are familiar with the nature extra cell matrix, and can be injected into defect location by syringe needle to realize the minimally invasive surgical technology in cartilage tissue engineering for the effective decrease of patients’operation burden. The hydrogels are one kind of very promising biomaterials in cartilage regeneration. Microspheres own preferable properties in drug delivery system, adjust the drug release rate to prolong the pharmacological function, decrease the times in drug supply to reduce the side effect, embed the drug to avoid the inactivation, also growth factors and cells can be embedded or implanted. We prepared injectable oxidative chondroitin sulfate (OCS)/ carboxymethyl chitosan (CMCS) hydrogel by Schiff base and gelatin microspheres loaded heparin by emulsification, and integrated gelatin microspheres into the hydrogel to the combination of micosphere’s drug delivery system and hydrogel’s injectability. We prepared injectable composite hydrogel systems with gelatin microspheres loaded heparin for cartilage regeneration engineering, and researched the composite hydrogels’ structure and properties. These work played important and significative role in the design and preparation of injectable hydrogel scaffolds used in cartilages’ repair and regeneration.Oxidative chondroitin sulfate (OCS) was obtained by adding sodium periodate (NaIO4) to chondroitin sulfate solution, the generated aldehyde group and the amino group in carboxymethyl chitosan molecule reacted through the schiff base. We prepared the injectable hydrogels based on the different volume ration (Vocs/Vcmcs). With the volume ration (Vocs/Vcmcs) decreased, the gelation time increased from about 1 min to about 2 min, the equilibrium swelling degree increased from 144% to 346%, the compressive modulus increased from about 2.6 kPa to about 4.0 kPa, also the hydrogels show more stable in PBS solution.The gelatin microspheres loaded heparin were prepared by emulsification, of which the prepared parameters were improved on the original basis. This method is easy to operate, owns high repeatability and spheres rate. The prepared gelatin microspheres showed the light yellow powders which were diffused seriatim. We observed the physical microstructure of gelatin microspheres by SEM, and measured the heparin encapsulation efficiency, the heparin loading capacity, and the drug release properties. Gelatin microspheres owned the porous structure and water absorption was about 280%. The embedded heparin effected the microspheres’ stability, excess loaded heparin accelerated the degradation behavior. The gelatin microspheres showed the sustained drug release effect, and the burst release happened in the initial stage.To combine the drug delivery release and the injectability operation, we integrated gelatin microspheres loaded 1% heparin into hydrogel (Vocs/Vcmcs=1:3) to prepare composite hydrogel system for cartilage repair and regeneration. The addition of microspheres influenced the whole systems’ gelation time, degradation stability, mechanical property and so on. With the increase of gelatin microspheres content, the composite hydrogels owned better compressive modulus, less degradation ratio while the gelation time became shorter and the maximum compressive deformation was decreased. The gelatin microspheres were coated by hydrogels which slowed down the heparin release rate, prolonged the drug effective and avoided the toxic side effect caused by burst release. The composite hydrogels with 3% microspheres showed more comprehensive physical properties and were more potential for the cartilage repair and regeneration.