Krell Ethan S, Ippolito Joseph A, Montemurro Nicholas J, Lim Phillip H, Vincent Richard A, Hreha Jeremy, Cottrell Jessica, Sudah Suleiman Y, Muñoz Maximilian F, Pacific Kristen P, Benevenia Joseph, OʼConnor J Patrick, Lin Sheldon S
*Department of Orthopaedics, Rutgers New Jersey Medical School, Newark, NJ; †Department of Biological Sciences, Seton Hall University, South Orange, NJ; and ‡Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ.
J Orthop Trauma. 2017 Mar;31(3):168-174. doi: 10.1097/BOT.0000000000000748.
This study examined the efficacy of calcium sulfate (CaSO4) as a carrier for intramedullary delivery of zinc chloride (ZnCl2) to treat fracture healing in a BB Wistar rat model. A non-carrier-mediated injection of 3.0 mg/kg of ZnCl2 has previously been shown to enhance fracture healing.
A heterogeneous mixture of ZnCl2 and CaSO4 was administered into the intramedullary femoral canal and a mid-diaphyseal femur fracture was created unilaterally. Early and late parameters of fracture healing were assessed using biomechanical testing, radiographic scoring, quantitative histomorphometry (for percentage of new cartilage and bone within the fracture callus), and long-term histologic evaluation.
Fractures treated with 1.0 mg/kg of ZnCl2/CaSO4 demonstrated a significantly higher maximum torque to failure compared with both CaSO4 (P = 0.048) and saline (P = 0.005) controls at 4 weeks postfracture (396.4 versus 251.3 versus 178.7 N mm, respectively). Statistically significant increases in torsional rigidity, effective shear modulus, and effective shear stress were also found, as well as a 3.5 times increase in radiographic score (based on bone union). Histologic examination of the fracture callus indicated enhanced chondrogenesis at day 14 postfracture, with increased percent cartilage for the ZnCl2/CaSO4 group compared with saline (P = 0.0004) and CaSO4 (P = 0.0453) controls. Long-term radiographic and histologic evaluation revealed no abnormal bone formation or infection up to 12 weeks postoperatively.
The effective dose of ZnCl2 augmentation for the enhancement of fracture healing in rats was reduced 3-fold in this study compared with previous findings. Furthermore, CaSO4 acted synergistically with ZnCl2 to increase the mechanical strength and stability at the fracture site.
本研究在BB Wistar大鼠模型中检测了硫酸钙（CaSO4）作为氯化锌（ZnCl2）髓内给药载体以治疗骨折愈合的疗效。先前已证明非载体介导的3.0 mg/kg ZnCl2注射可促进骨折愈合。
将ZnCl2和CaSO4的异质混合物注入股骨髓腔内，并单侧制造股骨干中段骨折。使用生物力学测试、影像学评分、定量组织形态计量学（用于骨折痂内新软骨和骨的百分比）以及长期组织学评估来评估骨折愈合的早期和晚期参数。
与硫酸钙（P = 0.048）和生理盐水（P = 0.005）对照组相比，在骨折后4周，用1.0 mg/kg ZnCl2/CaSO4治疗的骨折显示出显著更高的最大破坏扭矩（分别为396.4、251.3和178.7 N·mm）。还发现扭转刚度、有效剪切模量和有效剪应力有统计学意义的增加，以及影像学评分（基于骨愈合）增加了3.5倍。骨折痂的组织学检查表明，在骨折后第14天软骨形成增强，与生理盐水（P = 0.0004）和硫酸钙（P = 0.0453）对照组相比，ZnCl2/CaSO4组的软骨百分比增加。长期影像学和组织学评估显示，术后12周内无异常骨形成或感染。
与先前的研究结果相比，本研究中增强大鼠骨折愈合的ZnCl2有效剂量降低了3倍。此外，CaSO4与ZnCl2协同作用，增加了骨折部位的机械强度和稳定性。
