Biomineralized biomimetic organic/inorganic hybrid hydrogels based on hyaluronic acid and poloxamer

• Published in: Carbohydrate polymers 2015-08, Vol.126, p.130-140
• Main Authors: Huh, Hyun Wook, Zhao, Linlin, Kim, So Yeon
• Format: Article
• Language: English
• Subjects: Biomimetics; Biomineralization; Bone Substitutes - administration & dosage; Bone Substitutes - chemistry; Bone Substitutes - metabolism; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug Liberation; Humans; Hyaluronic acid; Hyaluronic Acid - administration & dosage; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; Hyaluronoglucosaminidase - metabolism; Hydrogel; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - metabolism; Injections; Models, Molecular; Poloxamer; Poloxamer - administration & dosage; Poloxamer - chemistry; Poloxamer - metabolism; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Propylene Glycols - administration & dosage; Propylene Glycols - chemistry; Propylene Glycols - metabolism; Temperature
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.03.033

•Biomineralized organic/inorganic hybrid HA/poloxamer hydrogels were prepared.•We investigated their feasibility as injectable hydrogel system to improve bone regeneration.•After biomineralization, a hydroxylapatite crystalline formation was observed in the hydrogels.•The hydrogel was injectable at 25°C, whereas it had a more rigid structure as temperature increased.•The drug release of the hydrogels was dependent on the DLC, water content, and biomineralization. A biomineralized hydrogel system containing hyaluronic acid (HA) and poloxamer composed of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO–PPO–PEO) block copolymer was developed as a biomimetic thermo-responsive injectable hydrogel system for bone regeneration. Using HA and poloxamer macromers with polymerizable residues, organic/inorganic HA/poloxamer hydrogels with various compositions were prepared and subjected to a biomineralization process to mimic the bone extracellular matrix. An increase in HA content within the hydrogels enhanced intermolecular chelation with calcium ions, leading to an increase in nucleation and growth of calcium phosphate in the hydrogels. After the biomineralization procedure, a crystalline formation was observed within and on the surface of the hydrogel. All of the HA/poloxamer hydrogel samples exhibited relatively high water content of greater than 90% at 25°C, and the water content was influenced by the HA/poloxamer composition, biomineralization, and temperature. In particular, the HA/poloxamer hydrogel was injectable through a syringe without demonstrating appreciable macroscopic fracture at room temperature, whereas it was more opaque and adopted a more rigid structure as the temperature increased because of the increasing hydrophobicity of poloxamer. The enzymatic degradation behavior of the hydrogels depended on the concentration of hyaluronidase, HA/poloxamer composition, and biomineralization. The release kinetics of model drugs from HA/poloxamer hydrogels was primarily dependent on the drug loading content, water content, biomineralization of the hydrogels, and ionic properties of the drug. These results indicate that biomineralized HA/poloxamer hydrogel is a promising candidate material for a biomimetic hydrogel system that promotes bone tissue repair and regeneration via local delivery of drugs.