| Surface modification is an effective approach to promote the bone regeneration after biomaterial implantation. Bone regeneration is highly dependent on microenvironments of the extracellular matrix (ECM). ECM comprises micro/nanostructured networks facilitating cell attachment and growth. ECM also contains signaling biomolecules that regulate cell activity and bone regeneration. This work focuses on designing a biomimetic microenvironment with multiple features of natural ECM on the surfaces of implants, which have both micro/nano stuctures and growth factor release system so as to improve osteointegration of implants.Bone morphology protein-2 (BMP-2) encapsulated chitosan/chondrotin sulfate nanoparticles(CHI/CS NPs) are developed to enhance ectopic bone formation on biphasic calcium phosphate (BCP) scaffolds. BMP-2 contained CHI/CS NPs were prepared by a simple and mild polyelectrolyte complexation process. It does not involve harsh organic solvents and high temperature, and therefore retain growth factors activity. These NPs were immobilized on BCP scaffolds, and realize the sustained release of growth factors from the scaffolds. The bare BCP scaffolds, NP loaded scaffolds (BCP-NP), and NPs loaded and polydopamine-coated scaffolds (BCP-Dop-NP) were seeded BMSC to evaluate the osteoinductivity of the scaffolds. BMSC culture results indicate that all scaffolds favor cell adhesion, proliferation, and differentiation. The BMP encapsulated NPs on BCP scaffolds provide a favorable environment for proliferation and differentiation of BMSC, and the released BMP-2 plays a key factor in the early stages of osteogenic differentiation.Afterwards, bare BCP, BCP-NP and BCP-Dop-NP scaffolds were implanted into rabbits intramuscularly to evaluate the ectopic bone formation of scaffolds. In vivo results indicate that BCP-NP and BCP-Dop-NP scaffolds enhance more ectopic bone formation than bare BCP scaffolds, which demonstrates that BMP-2 encapsulated polysaccharide NPs are effective to improve the osteoinductivity of the scaffolds.Porous scaffolds for tissue regeneration are often functionalized with extracellular matrix (ECM) proteins to enhance surface/cell interactions and tissue regeneration. However,continuous coatings produced by commonly used surface modification strategies might preclude cells from contacting and sensing the chemical and physical cues of the scaffold.Here we show that poly dopamine nanoparticles (PDA-NPs) tightly adhere on various scaffolds to form nanostructures, and the coverage can be finely tuned. Furthermore, the PDA-NPs have good affinity to a variety of proteins and peptides. Thus, the PDA-NPs act as anchor to immobilize signal biomolecules on scaffolds, and consequently promote cell activity and tissue regeneration. (3-tricalcium phosphate (TCP) scaffolds decorated with PDA-NPs demonstrate excellent osteoinductivity and bone regeneration performance due to the protein affinity of PDA-NPs and the intrinsic bioactive characteristics of TCP scaffolds.The PDA-NPs enhance the adsorbtion of ECM proteins on TCP scaffolds, and also realize the sustained release of BMP-2. Besides, PDA-NPs and their adsorbed BMP-2 synergistically enhance the activity of BMSCs in vitro, as well as induce new bone formation in vivo. In summary, PDA-NPs with excellent adhesiveness protein affinity is a versatile platform to modify porous scaffolds while not compromise the biological functions of the scaffolds, and might have potential applications in tissue regeneration.Bio-adhesive microporous architectures mimicking the functions of natural extracellular matrix (ECM) were prepared by self-assembling polydopamine (PDA) microcapsules, which not only favor cell adhesion and growth, but also facilitate growth factor immobilization and release. PDA coated polystyrene (PS) microspheres are synthesized by polymerization of dopamine on sulfonated PS microspheres and then assembled using positively charged CHI layers as link agents. After the PS core templates were removed, microporous architectures composed of PDA microcapsules were obtained. The produced microporous PDA architectures have high capability of adsorbing BMP-2 and realize the sustained release of BMP-2. More importantly, the bio-adhesive micro architecture and its immobilized BMP-2 synergistically enhance the activity and osteogenetic differentiation of bone marrow mesenchymal stem cells (BMSCs). Both super cell adhesion and BMP-2 immobilization ability of these architectures are attributed to the intrinsic adhesive nature of PDA and the porous architectures by assembly of PDA microcapsules. The bio-adhesive microporous PDA architectures with both cell affinitive and GF release features have a great potential to mimic natural ECM for modifying various medical devices in the fields of tissue engineering and regenerative medicine.Nanostructured architectures were produced on Ti surfaces by layer-by layer (LbL)self-assembling of polysaccharide coated BSA nanoparticles (BNPs), which creates cellular microenvironments mimicking natural extracellular matrix. The BMP-2 encapsulated BNPs were prepared by a desolvation method, and were further coated by chitosan (CHI) coatings to obtain positively charged NPs (CBNPs). Vancomycin (Van) encapsulated CBNPs were obtained by the same method and were subsequently coated by oxidized alginate (OALG) to obtain negatively charged NPs (OCBNPs). The CBNPs and OCBNPs were assembled Ti surfaces to construct nanostructured coatings via electrostatic and covalent interactions. The nanostructured architectures realize the sustained release of BMP-2 and Van for a long term.Bone marrow stromal cells (BMSCs) culture tests confirmed that the bare nanostructured architectures intrinsically facilitate attachment, proliferation, and differentiation of cells,which is attributed to the nanosize porous structures that are in the same size of cellular filopodia. Incorporating BMP-2 into the nanostructured architectures significantly enhance osteogenetic differentiation of BMSCs, which reveals the synergistic effects of nanostructures and growth factors on cell activity. The antibacterial tests indicated that controlled release of Van has good antibacterial ability against S. epidermidis, while does not affect the normal biological activity of BMSCs.CaP/polymer biomimetic structures were constructed with high drug loading ability and strong adhesive properties. Firstly, hydroxyapatite nanoparticles (HA-NPs) were prepared by the chemical synthesis method. Then, the HA-NPs were coated with poly dopamine (PDA)layers to obtain PDA-coated HA-NPs (PHA). Adhesive PDA nanoparticles (PDA-NPs) were synthesized by oxidation and self-polymerization of dopamine. Then, the PHA-NPs and PDA-NPs are assembled on Ti surfaces to construct nanostructured coatings due to the adhesion of PDA-NPs. The produced nano architectures have high capability of adsorbing BMP-2 and realize the sustained release of BMP-2 for a long period. Finally, BMSCs culture confirmed that the bare nanostructured coatings intrinsically facilitate attachment of cells,which is attributed to the adhesive properties of PDA and the nanoscale porous structures of coatings. The in vivo study show that the HA and BMP-2 synergistically enhance on cell activity and bone regeneration. |
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