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Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12847-52. doi: 10.1073/pnas.1408035111. Epub 2014 Aug 18.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.

Author information

1
Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
2
Restituo LLC, Cambridge, MA 02138;
3
Department of Oral Medicine, Infection and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA 02115;
4
Tissue Engineering Laboratories, Veterans Affairs Boston Healthcare System, Boston, MA 02130; and Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
5
Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; hammond@mit.edu.

Abstract

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.

KEYWORDS:

biomaterial; controlled drug release; layer-by-layer; regenerative medicine; wound healing

PMID:
25136093
PMCID:
PMC4156697
DOI:
10.1073/pnas.1408035111
[Indexed for MEDLINE]
Free PMC Article

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