Targeted protein delivery:carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds  

作　　者：Constantin Edi Tanase Omar Qutachi Lisa J.White Kevin M.Shakesheff Andrew W.McCaskie Serena M.Best Ruth E.Cameron 

机构地区：[1]Department of Materials Science and Metallurgy,University of Cambridge,Cambridge Centre for Medical Materials,Cambridge,27,Charles Babbage Road,CB30FS,UK [2]Centre for Biomolecular Sciences,School of Pharmacy,University of Nottingham,University Park,Nottingham NG72RD,UK [3]Division of Trauma&Orthopaedic Surgery,Department of Surgery,University of Cambridge,Box 180,Addenbrooke’s Hospital,Hills Road,Cambridge CB20QQ,UK [4]Present address:School of Pharmacy,De Montforte University,Leicester LE19BH,UK

出　　处：《Regenerative Biomaterials》2019年第5期279-287,共9页再生生物材料（英文版）

基　　金：the European Research Council[ERC Advanced Grant 3205983D-E];the Medical Research Council,Arthritis Research UK,Reumafonds and the UKRMP。

摘　　要：Tissue engineering response may be tailored via controlled,sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional(3D)ice-templated collagen scaffolds.However,the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored.Here,we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide)microparticles.We probe the effects of subsequent N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride crosslinking on protein release,using microparticles with different internal protein distributions.Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug.The scaffolds display a homogeneous microparticle distribution,and a reduction in pore size and percolation diameter with increased microparticle addition,although these values did not fall below those reported as necessary for cell invasion.The protein distribution within the microparticles,near the surface or more deeply located within the microparticles,was important in determining the release profile and effect of crosslinking,as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold.Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release.Protein located within the bulk of the microparticles,was protected from the crosslinking reaction and no delay in the overall release profile was seen.

关 键 词：collagen scaffolds PLGA microparticles FITC-BSA EDC crosslinking pore size percolation diameter 

分 类 号：R31[医药卫生—基础医学]