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Edited by Kristi S. Anseth, Howard Hughes Medical Institute, University of Colorado, Boulder, CO, and approved July 23, 2014 (received for review May 1, 2014)
Significance
A critical challenge in the field of tissue repair is effective bone repair and reconstruction. The clinical standard of extracting bone from another area in the body or from donors is severely hampered by short supply, pain, and concerns about disease transmission. In this study, we developed a polymer-based nanolayered coating that carries active biological drugs in physiologically relevant amounts for tissue repair, with tunable release properties to induce bone repair. Using a rodent model, we observed that these coatings yield mature, mechanically stable bone that bridges large defects and restores the native form. This system is a potent strategy for safe and precise tissue repair and has the potential to significantly boost successful outcomes for bone repair.
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.
Footnotes
- ↵1To whom correspondence should be addressed. Email: hammond{at}mit.edu.
Author contributions: N.J.S., M.N.H., and P.T.H. conceived the idea and designed the study; N.J.S., M.N.H., M.A.Q., and N.-M.D.C. performed experiments; N.J.S., M.N.H., M.A.Q., N.-M.D.C., H.J.S., M.N., M.S., and P.T.H. analyzed data; and N.J.S., M.N.H., M.A.Q., N.-M.D.C., H.J.S., M.N., M.S., and P.T.H. wrote the paper.
Conflict of interest statement: H.J.S. is an employee at Bioventus LLC, owns stock in, and is a paid consultant for, Pfizer, Inc.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1408035111/-/DCSupplemental.
Adaptive growth factor delivery for bone repair
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