Malcolm R DeBaun1, Brett P Salazar2, Yan Bai3, Michael J Gardner4, Yunzhi Peter Yang5, Chi-Chun Pan6, Alex Martin Stahl7, Seydesina Moeinzadeh2, Sungwoo Kim2, Elaine Lui6, Carolyn Kim6, Sien Lin2, L Henry Goodnough2, Harsh Wadhwa2. 1. Department of Orthopaedic Surgery, Duke University, NC, USA. 2. Department of Orthopaedic Surgery, Stanford University, CA, USA. 3. Department of Orthopaedic Surgery, Stanford University, CA, USA; School of Pharmacy, Chongqing Medical University, Chongqing, China. 4. Department of Orthopaedic Surgery, Stanford University, CA, USA. Electronic address: michaelgardner@stanford.edu. 5. Department of Orthopaedic Surgery, Stanford University, CA, USA; Department of Mechanical Engineering, Stanford University, CA, USA; Department of Bioengineering, Stanford University, CA, USA. Electronic address: ypyang@stanford.edu. 6. Department of Orthopaedic Surgery, Stanford University, CA, USA; Department of Mechanical Engineering, Stanford University, CA, USA. 7. Department of Chemistry, Stanford University, CA, USA.
Abstract
OBJECTIVES: High energy long bone fractures with critical bone loss are at risk for nonunion without strategic intervention. We hypothesize that a synthetic membrane implanted at a single stage improves bone healing in a preclinical nonunion model. METHODS: Using standard laboratory techniques, microspheres encapsulating bone morphogenic protein-2 (BMP2) or platelet derived growth factor (PDGF) were designed and coupled to a type 1 collagen sheet. Critical femoral defects were created in rats and stabilized by locked retrograde intramedullary nailing. The negative control group had an empty defect. The induced membrane group (positive control) had a polymethylmethacrylate spacer inserted into the defect for four weeks and replaced with a bare polycaprolactone/beta-tricalcium phosphate (PCL/β-TCP) scaffold at a second stage. For the experimental groups, a bioactive synthetic membrane embedded with BMP2, PDGF or both enveloped a PCL/β-TCP scaffold was implanted in a single stage. Serial radiographs were taken at 1, 4, 8, and 12 weeks postoperatively from the definitive procedure and evaluated by two blinded observers using a previously described scoring system to judge union as primary outcome. RESULTS: All experimental groups demonstrated better union than the negative control (p = 0.01). The groups with BMP2 incorporated into the membrane demonstrated higher average union scores than the other groups (p = 0.01). The induced membrane group performed similarly to the PDGF group. Complete union was only demonstrated in groups with BMP2-eluting membranes. CONCLUSIONS: A synthetic membrane comprised of type 1 collagen embedded with controlled release BMP2 improved union of critical bone defects in a preclinical nonunion model.
OBJECTIVES: High energy long bone fractures with critical bone loss are at risk for nonunion without strategic intervention. We hypothesize that a synthetic membrane implanted at a single stage improves bone healing in a preclinical nonunion model. METHODS: Using standard laboratory techniques, microspheres encapsulating bone morphogenic protein-2 (BMP2) or platelet derived growth factor (PDGF) were designed and coupled to a type 1 collagen sheet. Critical femoral defects were created in rats and stabilized by locked retrograde intramedullary nailing. The negative control group had an empty defect. The induced membrane group (positive control) had a polymethylmethacrylate spacer inserted into the defect for four weeks and replaced with a bare polycaprolactone/beta-tricalcium phosphate (PCL/β-TCP) scaffold at a second stage. For the experimental groups, a bioactive synthetic membrane embedded with BMP2, PDGF or both enveloped a PCL/β-TCP scaffold was implanted in a single stage. Serial radiographs were taken at 1, 4, 8, and 12 weeks postoperatively from the definitive procedure and evaluated by two blinded observers using a previously described scoring system to judge union as primary outcome. RESULTS: All experimental groups demonstrated better union than the negative control (p = 0.01). The groups with BMP2 incorporated into the membrane demonstrated higher average union scores than the other groups (p = 0.01). The induced membrane group performed similarly to the PDGF group. Complete union was only demonstrated in groups with BMP2-eluting membranes. CONCLUSIONS: A synthetic membrane comprised of type 1 collagen embedded with controlled release BMP2 improved union of critical bone defects in a preclinical nonunion model.
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