Fabrication Of Dopamine-Modified Biomacromolecule Gradient Scaffolds And Property Regulation

With increasing of bone defects such as bone trauma,osteomyelitis,bone tumor,more types and higher performances of bone repair scaffolds are required.Native bone consists of complex gradient structures.The traditional bone repair scaffolds with uniform structures could not effectively support the regeneration of bone tissue.In addition,the interaction between scaffolds and cells or tissues is clinically vital for long-term performances of bone repair scaffolds.However,the traditional bone repair scaffolds still lack the cell recognition sites,resulting in the weak binding to the surrounding tissues.This drawback is not conducive to cell adhesion,proliferation and tissue regeneration.Therefore,preparation of the ideal bone repair scaffolds not only need to mimic the gradient structures of native bone but also need to effectively improve the interaction with cells and tissues.Herein,dopamine(DA)with superior adhesion and excellent reactivity was used to modifiy biomacromolecules.Then,the modified biomacromolecules were compounded with nanomaterials to fabricate the dopamine-modified gradient scaffolds.The micro-architecture including pore sizes,porosities and the properties of mechanical properties,degradation rates,mineralization properties,drug loading and release properties,biocompatibilities,cell adhesion and osteogenic activities of gradient scaffolds were investigated in detail.1.Fabrication of polydopamine/dopamine-modified alginate gradient scaffolds and property regulationIn this study,dopamine-modified alginate(Alg-DA)with excellent adhesion property was synthesized by grafting DA onto Alg.Using the self-polymerization of DA,polydopamine nanoparticles(PDA NPs)with controlled particle sizes were prepared.Alg-DA with different concentrations were compounded with PDA NPs,and then the PDA/Alg-DA gradient scaffolds were fabricated through freeze-drying method.To study the effects of DA and PDA NPs on the structures and properties of each layer of gradient scaffolds,Alg,PDA/Alg,Alg-DA and PDA/Alg-DA homogenous scaffolds were also prepared by freeze-drying.Scanning electron microscopy(SEM)results showed that the pore structures of gradient scaffolds were regular,and the pore sizes displayed gradient distribution.The individual layers were seamlessly integrated with one another.A high degree of pore interconnectivity throughout the construct could also be observed,with a high porosity about 76%.The compressive modulus of PDA/Alg-DA gradient scaffolds reached 0.93 MPa when the strain was 10%.The degradation,mineralization and drug loading and release properties of the scaffolds were further investigated.The results showed that the degradation rates of gradient scaffolds were approximately 14% after degrating 35 days,and these scaffolds possessed good mineralization performances which could effectively promote the deposition of calcium phosphate.Moreover,PDA/Alg-DA gradient scaffolds had high drug loading rates and could realize the slow release of drugs.The results of MTT assay and FDA staining indicated that the gradient scaffolds displayed good cytocompatibilities and high cell viabilities.SEM images showed that cells were firmly adhered to the surface and the internal pores of gradient scaffolds,indicating good cell adhesion of the scaffolds.The effects of DA and PDA NPs on the structures and properties of PDA/Alg-DA gradient scaffolds were also studied,and the results showed that the pore sizes,porosities and the degradation rates of gradient scaffolds were reduced after modifying with DA and PDA NPs,while the mechanical properties,mineralization performances,drug loading and release properties and cell adhesion were significantly improved.2.Fabrication of hydroxyapatite/dopamine-modified alginate gradient scaffolds and property regulationTo improve the mechanical property and osteogenic activity,hydroxyapatite was introduced compound with Alg-DA to fabricate gradient scaffolds.Quaternized chitosan(QCS)with high charge density was synthesized by reacting chitosan(CS)with 3-chloro-2-hydroxypropyltrimethylammonium chloride(CHPTAC)in alkali/urea aqueous solution.Biomimetic synthesis had drawn extensive attention because it could simulate the process of hydroxyapatite(HA)nucleation and growth occurred in native bone.In this work,a novel quaternized chitosan-templated hydroxyapatite(QCHA)was synthesized by biomimetic strategy in the presence of QCS as template.The QCHA/Alg-DA gradient scaffolds were fabricated through freeze-drying method.The microstructures,porosities,mechanical properties,degradabilities,mineralization performances,drug loading and release properties,biocompatibilities,cell adhesion and osteogenic properties were investigated in detail.The resultant QCHA/Alg-DA gradient scaffolds were found to have continuous pore structures,and the pore sizes were gradient distribution which decreased with the increase of QCHA.The gradient scaffolds also showed a high level of porosity about 72%.The gradient scaffolds displayed good mechanical properties,and the compressive modulus of the individual layer increased with the increase of QCHA.When the strain was 10%,the compressive modulus reached 1.70 MPa.The degradation rates of gradient scaffolds were approximately 30% after degrating 35 days,which were suitable to new bone regenation.The mineralization properties of gradient scaffolds were excellent,which could accelerate the deposition of calcium phosphate on the scaffolds.The interactions between Alg-DA and drugs made the gradient scaffolds had high immobilization capabilities and achieved slow release of drugs.In addition,QCHA/Alg-DA gradient scaffolds also possessed good biocompatibilities which were conducive to cell adhesion and proliferation.The results of animal experimental indicated that the gradient scaffolds had good histocompatibilities and osteogenetic activities,which were advantageous to the regeneration and reconstruction of bone tissue.In this study,two kinds of dopamine-modified biomacromolecule gradient scaffolds mimicked the inherent gradient structure of native bone were fabricated through good structure design.These gradient scaffolds were shown to have gradient pore structures,high levels of porosities,good mechanical properties,appropriate degradation rates,good immobilization and release properties as well as excellent mineralization performances.Moreover,the high cell viabilities,good cell adhesion and good osteogenic activities were evident,demonstrating the potential of these gradient scaffolds as an advanced strategy for bone defect repair.