title: Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.
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.
authors.affiliation: Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Nisarg J
authors.initials: NJ
authors.lastname: Shah
authors.affiliation: Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Md Nasim
authors.initials: MN
authors.lastname: Hyder
authors.affiliation: Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Mohiuddin A
authors.initials: MA
authors.lastname: Quadir
authors.affiliation: Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Noémie-Manuelle
authors.initials: NM
authors.lastname: Dorval Courchesne
authors.affiliation: Restituo LLC, Cambridge, MA 02138;
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Seeherman
authors.affiliation: Department of Oral Medicine, Infection and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Boston, MA 02115;
authors.forename: Myron
authors.initials: M
authors.lastname: Nevins
authors.affiliation: 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.
authors.forename: Myron
authors.initials: M
authors.lastname: Spector
authors.affiliation: Department of Chemical Engineering and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; hammond@mit.edu.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D019386:Alendronate / Q000494:pharmacology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D001672:Biocompatible Materials / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D004195:Disease Models, Animal; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D008567:Membranes, Artificial; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044968:Regenerative Medicine / Q000379:methods*; D012886:Skull / Q000187:drug effects* / Q000293:injuries; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D008567:Membranes, Artificial; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019386:Alendronate
keywords: biomaterial; controlled drug release; layer-by-layer; regenerative medicine; wound healing