Georgia Institute of Technology, Institute for Bioengineering and Bioscience, 315 Ferst Drive, Atlanta, GA 30332, USA.
Clin Orthop Relat Res. 2011 Nov;469(11):3111-7. doi: 10.1007/s11999-011-2012-x.
Bone defects and fracture nonunions remain a substantial challenge for clinicians. Grafting procedures are limited by insufficient volume and donor site morbidity. As an alternative, biomaterial scaffolds functionalized through incorporation of growth factors such as bone morphogenetic proteins (BMPs) have been developed and appear to regenerate the structure and function of damaged or degenerated skeletal tissue.
OBJECTIVES/PURPOSES: Our objectives were therefore to determine whether: (1) the addition of heparin alone to collagen scaffolds sufficed to promote bone formation in vivo; (2) collagen-heparin scaffold improved BMP-mediated bone regeneration; and (3) precomplexed heparin and BMP-2 delivered on collagen scaffold could restore long bone biomechanical strength.
We created bilateral surgical defects in the femora of 20 rats and filled the defects with PCL scaffolds with one of five treatments: collagen matrix (n = 5), collagen/heparin matrix (n = 7), collagen matrix + BMP-2 (n = 9), collagen/heparin matrix + BMP-2 (n = 9), or collagen matrix + BMP-2/heparin complex (n = 9). Bone formation was observed with radiographs and micro-CT analysis and biomechanical testing was used to assess strength.
The addition of heparin alone to collagen did not promote bone ingrowth and the addition of heparin to collagen did not improve BMP-mediated bone regeneration. Delivery of precomplexed BMP-2 and heparin in a collagen matrix resulted in new bone formation with mechanical properties similar to those of intact bone.
Our findings suggest delivery of precomplexed BMP-2 and heparin may be an advantageous strategy for treatment of clinically challenging bone defects.
骨缺损和骨折不愈合仍然是临床医生面临的重大挑战。移植物的应用受到体积不足和供体部位发病率的限制。作为替代方法，已开发出通过掺入骨形态发生蛋白（BMPs）等生长因子对生物材料支架进行功能化的方法，这些方法似乎可以再生受损或退化的骨骼组织的结构和功能。
我们的目的是确定以下几点：（1）单独向胶原支架中添加肝素是否足以促进体内骨形成；（2）胶原-肝素支架是否改善了 BMP 介导的骨再生；（3）在胶原支架上预先复合的肝素和 BMP-2 能否恢复长骨的生物力学强度。
我们在 20 只大鼠的股骨中创建了双侧手术缺损，并将 PCL 支架填充到缺损中，其中有五种治疗方法：胶原基质（n = 5）、胶原/肝素基质（n = 7）、胶原基质+ BMP-2（n = 9）、胶原/肝素基质+ BMP-2（n = 9）或胶原基质+ BMP-2/肝素复合物（n = 9）。通过 X 射线和微 CT 分析观察骨形成，通过生物力学测试评估强度。
单独向胶原中添加肝素不能促进骨内生长，向胶原中添加肝素也不能改善 BMP 介导的骨再生。在胶原基质中递送预先复合的 BMP-2 和肝素可导致新骨形成，其机械性能与完整骨相似。
我们的研究结果表明，递送预先复合的 BMP-2 和肝素可能是治疗临床上具有挑战性的骨缺损的有利策略。
