Djordjevic Ivan, Pokholenko Oleksandr, Shah Ankur Harish, Wicaksono Gautama, Blancafort Lluis, Hanna John V, Page Samuel J, Nanda Himansu Sekhar, Ong Chee Bing, Chung Sze Ryn, Chin Andrew Yuan Hui, McGrouther Duncan, Choudhury Muntasir Mannan, Li Fang, Teo Jonathan Shunming, Lee Lui Shiong, Steele Terry W J
School of Materials Science and Engineering, Nanyang Technological University, 639798, Singapore.
Departamento de Química and Instituto de Química Computacional i Catálisis. Facultad de Ciències, Universidad de Girona, C/M.A. Capmany 69, 17003, Girona, Spain.
Biomaterials. 2020 Nov;260:120215. doi: 10.1016/j.biomaterials.2020.120215. Epub 2020 Jul 11.
Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a multipurpose platform for tissue mending. A fresh approach to bonding wet substrates has yielded a synthetic biomaterial that overcomes the drawbacks of free-radical and nature-inspired bioadhesives. A food-grade liquid polycaprolactone grafted with carbene precursors yields CaproGlu. The first-of-its-kind low-viscosity prepolymer is VOC-free and requires no photoinitiators. Grafted diazirine end-groups form carbene diradicals upon low energy UVA (365 nm) activation that immediately crosslink tissue surfaces; no pre-heating or animal-derived components are required. The hydrophobic polymeric environment enables metastable functional groups not possible in formulations requiring solvents or water. Activated diazirine within CaproGlu is uniquely capable of crosslinking all amino acids, even on wet tissue substrates. CaproGlu undergoes rapid liquid-to-biorubber transition within seconds of UVA exposure-features not found in any other bioadhesive. The exceptional shelf stability of CaproGlu allows gamma sterilization with no change in material properties. CaproGlu wet adhesiveness is challenged against current unmet clinical needs: anastomosis of spliced blood vessels, anesthetic muscle patches, and human platelet-mediating coatings. The versatility of CaproGlu enables both organic and inorganic composites for future bioadhesive platforms.
受对具有弹性体材料特性的强力组织粘合剂的临床需求驱动，人们寻求摒弃传统交联化学方法，打造一个用于组织修复的多功能平台。一种全新的粘合湿基材的方法产生了一种合成生物材料，它克服了自由基和天然灵感生物粘合剂的缺点。一种接枝有卡宾前体的食品级液态聚己内酯可生成CaproGlu。这种首创的低粘度预聚物不含挥发性有机化合物，且无需光引发剂。接枝的重氮端基在低能量紫外线A（365纳米）激活后形成卡宾双自由基，可立即交联组织表面；无需预热或使用动物源成分。疏水性聚合物环境使得在需要溶剂或水的配方中无法实现的亚稳官能团成为可能。CaproGlu中的活化重氮能够独特地交联所有氨基酸，即使是在湿组织基材上。CaproGlu在紫外线A照射几秒钟内即可从液体快速转变为生物橡胶，这是其他任何生物粘合剂都不具备的特性。CaproGlu出色的储存稳定性使其能够进行伽马灭菌，且材料性能不变。CaproGlu的湿粘性针对当前未满足的临床需求进行了验证：拼接血管的吻合、麻醉肌肉贴片以及人类血小板介导涂层。CaproGlu的多功能性为未来的生物粘合剂平台带来了有机和无机复合材料。
