Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

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

Nisarg J. Shah, Md. Nasim Hyder, Mohiuddin A. Quadir, Noémie-Manuelle Dorval Courchesne, Howard J. Seeherman, Myron Nevins, Myron Spector, and Paula T. Hammond
PNAS first published August 18, 2014; https://doi.org/10.1073/pnas.1408035111
Nisarg J. Shah
aDepartment of Chemical Engineering and
bThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Md. Nasim Hyder
aDepartment of Chemical Engineering and
bThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mohiuddin A. Quadir
aDepartment of Chemical Engineering and
bThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noémie-Manuelle Dorval Courchesne
aDepartment of Chemical Engineering and
bThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Howard J. Seeherman
cRestituo LLC, Cambridge, MA 02138;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Myron Nevins
dDepartment of Oral Medicine, Infection and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Myron Spector
eTissue Engineering Laboratories, Veterans Affairs Boston Healthcare System, Boston, MA 02130; and
fDepartment of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paula T. Hammond
aDepartment of Chemical Engineering and
bThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: hammond@mit.edu
  1. 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)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

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.

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

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.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Adaptive growth factor delivery for bone repair
Nisarg J. Shah, Md. Nasim Hyder, Mohiuddin A. Quadir, Noémie-Manuelle Dorval Courchesne, Howard J. Seeherman, Myron Nevins, Myron Spector, Paula T. Hammond
Proceedings of the National Academy of Sciences Aug 2014, 201408035; DOI: 10.1073/pnas.1408035111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Adaptive growth factor delivery for bone repair
Nisarg J. Shah, Md. Nasim Hyder, Mohiuddin A. Quadir, Noémie-Manuelle Dorval Courchesne, Howard J. Seeherman, Myron Nevins, Myron Spector, Paula T. Hammond
Proceedings of the National Academy of Sciences Aug 2014, 201408035; DOI: 10.1073/pnas.1408035111
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (4)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
Yellow emoticons
Learning the language of facial expressions
Aleix Martinez explains why facial expressions often are not accurate indicators of emotion.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490