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Linking of Bone Morphogenetic Protein‐2 To Resorbable Fracture Plates for Enhancing Bone Healing
Author(s) -
Shibuya Terry Y.,
Wadhwa Ashish,
Nguyen Kevin H.,
Panossian Abraham M.,
Kim Sanghun,
Wong Hausin,
Feinberg Steven,
Damisah Eyiyemisi C.,
Camilon P Ryan,
Bang Hoang
Publication year - 2005
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/01.mlg.0000183692.27532.5b
Subject(s) - covalent bond , carbodiimide , bone morphogenetic protein 2 , alkaline phosphatase , chemistry , horseradish peroxidase , bone morphogenetic protein , bone healing , staining , biochemistry , in vitro , enzyme , anatomy , organic chemistry , biology , genetics , gene
Objective: To test whether bone morphogenetic protein (BMP)‐2 may be covalently linked to resorbable fracture repair plates using an ester‐hydrolysis reaction and determining whether the linked compound can facilitate bone growth. Study Design: Laboratory in vitro experiments. Method: Resorbable fracture repair plates were partially hydrolyzed using varying concentrations of acid or base. This intermediate was then reacted with EDAC (1‐ethyl‐3[‐3‐dimethylamino propyl carbodiimide) to form an EDAC intermediate, which was then reacted with either horseradish peroxidase (HRP), interleukin (IL)‐2, or BMP‐2. Compound binding to the plate was confirmed by immunofluorescent staining. Confirmation of protein function was determined by the following assays: HRP's ability to cleave peroxide, IL‐2's ability to stimulate lymphocytes, and BMP‐2's ability to stimulate C3H10T1/2 cells to generate alkaline phosphatase. Results: Three compounds (HRP, IL‐2, and BMP‐2) were successfully linked to plates as confirmed by immunofluorescence staining or functional testing. Compounds demonstrated better covalent linking to plates under basic conditions. HRP, IL‐2, and BMP‐2 retained function after binding as measured by cleaved peroxide levels, lymphocytes proliferation, and alkaline phosphatase production. Conclusions: Covalent linking of compounds such as HRP, IL‐2, and BMP‐2 to resorbable plates is possible and represents a novel protein delivery technique. BMP‐2 covalently linked to resorbable plates may be used to facilitate bone healing. Covalent linking of compounds to plates represents a novel method for delivering concentrated levels of growth factors to a specific site and potentially extending their half‐life. Further investigation into this application for bone healing may lead to quicker healing.