Effective Immobilization of BMP-2 Mediated by Polydopamine Coating on Biodegradable Nanofibers for Enhanced in Vivo Bone Formation

Abstract

Although bone morphogenic proteins (BMPs) have been widely used for bone regeneration, the ideal delivery system with optimized dose and minimized side effects is still active area of research. In this study, we developed bone morphogenetic protein-2(BMP-2) immobilized poly(l-lactide) (PLLA) nanofibers inspired by polydopamine, which could be ultimately used as membranes for guided bone regeneration, and investigated their effect on guidance of in vitro cell behavior and in vivo bone formation. Surface chemical analysis of the nanofibers confirmed successful immobilization of BMP-2 mediated by polydopamine, and about 90% of BMP-2 was stably retained on the nanofiber surface for at least 28 days. The alkaline phosphatase activity and calcium mineralization of human mesenchymal stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively small dose was highly active following implantation to the critical-sized defect in the cranium of mice; radiographic analysis demonstrated that 77.8 ± 11.7% of newly formed bone was filled within the defect for a BMP-2-immobilized groups at the concentration of 124 ± 9 ng/cm(2), as compared to 5.9 ± 1.0 and 34.1 ± 5.5% recovery, for a defect-only and a polydopamine-only group, respectively. Scanning and transmission electron microscopy of samples from the BMP-2 immobilized group showed fibroblasts and osteoblasts with nanofiber strands in the middle of regenerated bone tissue, revealing the importance of interaction between implanted nanofibers and the neighboring extracellular environment. Taken together, our data support that the presentation of BMP-2 on the surface of nanofibers as immobilized by utilizing polydopamine chemistry may be an effective method to direct bone growth at relatively low local concentration.

Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications

“…Further microscopic analysis revealed the stability of polydopamine nanofiber surfaces and interaction between the modified nanofibers and host ECM ( Figure 5D, bottom side). 66 Enamel and dentin are major calcified components of dental tissue consisting of significant amounts of minerals with an organic matrix (mainly collagen) and water. Polydopamine coating has been utilized for mineralization of enamel and dentin since catecholamine moieties present in polydopamine exhibit high affinity to minerals and show accelerated hydroxyapatite crystal growth.…”

“…In another study, polydopamine-coated nanofibers implanted in mouse cranial defects showed the stable presence of a coated polydopamine layer, and further microscopic analysis revealed that host cells and regenerated collagen fibers closely interacted with the polydopamine surface throughout the nanofiber region with no signs of inflammation ( Figure 5D, bottom side). 66 Furthermore, applications of polydopamine in the area of medical devices have been explored. Gao et al developed heparin-immobilized PLLA membranes coated with polydopamine for hemodialysis, and in vitro experiments showed significant clearance of urea and lysozymes while 90% of BSA was retained, suggesting that surface heparinization through polydopamine improved material hemocompatibility and decreased the hemolysis ratio.…”

“…(D) Micro-CT revealed that PD-PLLA-BMP-2 scaffolds promoted greater bone regeneration than did unmodified PLLA nanofibers. TEM showed biocompatibility of polydopamine-coated nanofibers via the strong interaction of endogenous cells with regenerated collagen (Col; collagen, NF; PLLA nanofiber, PD; polydopamine layer) 66. …”

Polydopamine‐Modified Black Phosphorous Nanocapsule with Enhanced Stability and Photothermal Performance for Tumor Multimodal Treatments

“…PDA, produced by the oxidative polymerization of DA under weakly alkaline conditions, has been employed as a promising coating in the biological field due to their excellent biocompatibility, biodegradation, and pH response at low pH values 13. PDA coating can form extraordinary adhesion on nearly any substrate surfaces and further couple secondary biopolymers with amines/thiols via Michael addition or Schiff base reactions 14. Besides, PDA also has strong NIR absorbility and high photothermal conversion efficiency.…”

Electrochemical impedance and spectroscopy study of the EDC/NHS activation of the carboxyl groups on poly(ε-caprolactone)/poly(m-anthranilic acid) nanofibers

“…AFM images of PCL/P3ANA and albumin immobilized nanofibers were represented in Figure 7. The surface of PCL/P3ANA nanofibers retained its topography after covalent immobilization of albumin indicating the EDC and/or NHS were not assembled or remained [6,30]. In correlation with FTIR-ATR, EDX and BCA, AFM images also indicates that the highest amount of albumin bound to nanofibers activated with 50/50 mM of EDC/NHS.…”