Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation

Hyeong Jin Cho, Sajeesh Kumar Madhurakkat Perikamana, Ji Hye Lee, Jinkyu Lee, Kyung-Mi Lee, Choongsoo S. Shin, Heungsoo Shin

Research output: Contribution to journalArticle

88 Citations (Scopus)

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/cm2, 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.

Original languageEnglish
Pages (from-to)11225-11235
Number of pages11
JournalACS Applied Materials and Interfaces
Volume6
Issue number14
DOIs
Publication statusPublished - 2014 Jul 23

Fingerprint

Nanofibers
Bone
Proteins
Coatings
polydopamine
Defects
Bone Morphogenetic Protein 2
Osteoblasts
Fibroblasts
Phosphatases
Stem cells
Alkaline Phosphatase
Calcium

Keywords

  • bone morphogenic proteins
  • electrospinning
  • guided bone regeneration
  • nanofibers
  • osteogenic differentiation
  • polydopamine

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation. / Cho, Hyeong Jin; Madhurakkat Perikamana, Sajeesh Kumar; Lee, Ji Hye; Lee, Jinkyu; Lee, Kyung-Mi; Shin, Choongsoo S.; Shin, Heungsoo.

In: ACS Applied Materials and Interfaces, Vol. 6, No. 14, 23.07.2014, p. 11225-11235.

Research output: Contribution to journalArticle

Cho, Hyeong Jin ; Madhurakkat Perikamana, Sajeesh Kumar ; Lee, Ji Hye ; Lee, Jinkyu ; Lee, Kyung-Mi ; Shin, Choongsoo S. ; Shin, Heungsoo. / Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation. In: ACS Applied Materials and Interfaces. 2014 ; Vol. 6, No. 14. pp. 11225-11235.
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AB - 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/cm2, 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.

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