MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Moos Tower, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
Department of Diagnostic and Biological Sciences, University of Minnesota, Moos Tower, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
Mater Sci Eng C Mater Biol Appl. 2021 Jun;125:112108. doi: 10.1016/j.msec.2021.112108. Epub 2021 Apr 16.
Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e., non-responsive to biological cues. However, tissue remodeling necessary for implant integration features an ever-changing milieu of cells that demands a responsive biomaterial surface for temporal synchronization of interactions between biomaterial and tissue. Here, we successfully synthesized a multi-functional, dynamic coating on titanium by co-immobilizing GL13K antimicrobial peptide and an MMP-9 - a matrix metalloproteinase secreted by bone-remodeling osteoclasts - responsive peptide. Our co-immobilized peptide surface showed potent anti-biofilm activity, enabled effective osteoblast and fibroblast proliferation, and demonstrated stability against a mechanical challenge. Finally, we showed peptide release was triggered for up to seven days when the multi-peptide coatings were cultured with MMP-9-secreting osteoclasts. Our MMP-9 cleavable peptide can be conjugated with osteogenic or immunomodulatory motifs for enhanced bone formation in future work. Overall, we envisage our multifunctional, dynamic surface to reduce infection rates of percutaneous bone-anchored devices via strong anti-microbial activity and enhanced tissue regeneration via temporal synchronization between biomaterial cues and tissue responses.
将多种生物活性功能化到牙科和骨科植入物上,以获得具有改善的生物性能和降低感染率的表面,这是很理想的。虽然迄今为止已经探索了许多方法,但几乎所有功能化的表面都是静态的,即对生物信号没有反应。然而,组织重塑是植入物整合所必需的,其特征是细胞的微环境不断变化,这就需要一种响应性生物材料表面,以实现生物材料与组织之间相互作用的时间同步。在这里,我们通过共固定 GL13K 抗菌肽和 MMP-9(一种由骨重塑破骨细胞分泌的基质金属蛋白酶)响应肽,成功地在钛上合成了一种多功能的动态涂层。我们的共固定肽表面表现出强大的抗生物膜活性,能够有效促进成骨细胞和纤维细胞的增殖,并表现出对机械挑战的稳定性。最后,当多肽涂层与分泌 MMP-9 的破骨细胞共培养时,我们表明肽释放可以持续长达七天。在未来的工作中,我们可以将 MMP-9 可切割肽与成骨或免疫调节基序结合,以增强骨形成。总的来说,我们设想我们的多功能动态表面可以通过强大的抗菌活性降低经皮骨锚定装置的感染率,并通过生物材料线索和组织反应之间的时间同步来增强组织再生。