Orellana Bryan R, Hilt J Zach, Puleo David A
Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky.
J Biomed Mater Res B Appl Biomater. 2015 Jan;103(1):135-42. doi: 10.1002/jbm.b.33181. Epub 2014 Apr 30.
To help reduce the need for autografts, calcium sulfate (CS)-based bone graft substitutes are being developed to provide a stable platform to aid augmentation while having the ability to release a broad range of bioactive agents. CS has an excellent reputation as a biocompatible and osteoconductive substance, but addition of bioactive agents may further enhance these properties. Samples were produced with either directly loaded small, hydrophobic molecule (i.e., simvastatin), directly loaded hydrophilic protein (i.e., lysozyme), or 1 and 10 wt % of fast-degrading poly(β-amino ester) (PBAE) particles containing protein. Although sustained release of directly loaded simvastatin was achieved, direct loading of small amounts of lysozyme resulted in highly variable release. Direct loading of a larger amount of protein generated a large burst, 65% of total loading, followed by sustained release of protein. Release of lysozyme from 1 wt % of PBAE particles embedded into CS was more controllable than when directly loaded, and for 10 wt % of protein-loaded PBAE particles, a higher burst was followed by sustained release, comparable to the results for the high direct loading. Compression testing determined that incorporation of directly loaded drug or drug-loaded PBAE particles weakened CS. In particular, PBAE particles had a significant effect on the strength of the composites, with a 25 and 80% decrease in strength for 1 and 10 wt % particle loadings, respectively. CS-based composites demonstrated the ability to sustainably release both macromolecules and small molecules, supporting the potential for these materials to release a range of therapeutic agents.
为了减少自体移植的需求，正在开发基于硫酸钙（CS）的骨移植替代物，以提供一个稳定的平台来辅助骨增量，同时具备释放多种生物活性剂的能力。CS作为一种生物相容性和骨传导性物质享有盛誉，但添加生物活性剂可能会进一步增强这些特性。制备了分别直接负载小分子疏水分子（即辛伐他汀）、直接负载亲水性蛋白质（即溶菌酶）或含有1 wt%和10 wt%蛋白质的快速降解聚（β-氨基酯）（PBAE）颗粒的样品。虽然实现了直接负载的辛伐他汀的持续释放，但直接负载少量溶菌酶会导致释放高度可变。直接负载大量蛋白质会产生一个大的突释，占总负载量的65%，随后是蛋白质的持续释放。从嵌入CS的1 wt% PBAE颗粒中释放溶菌酶比直接负载时更可控，对于10 wt%负载蛋白质的PBAE颗粒，较高的突释之后是持续释放，这与高直接负载量的结果相当。压缩测试确定，直接负载药物或负载药物的PBAE颗粒的加入会削弱CS。特别是，PBAE颗粒对复合材料的强度有显著影响，对于1 wt%和10 wt%的颗粒负载量，强度分别降低25%和80%。基于CS的复合材料显示出可持续释放大分子和小分子的能力，支持了这些材料释放一系列治疗剂的潜力。
