Erratum: In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging

Abstract

The design of erodible biomaterials relies on the ability to program the in vivo retention time, which necessitates real-time monitoring of erosion. However, in vivo performance cannot always be predicted by traditional determination of in vitro erosion 1,2 , and standard methods sacrifice samples or animals 3 , preventing sequential measures of the same specimen. We harnessed non-invasive fluorescence imaging to sequentially follow in vivo material-mass loss in order to model the degradation of materials hydrolytically (PEG:dextran hydrogel) and enzymatically (collagen). Hydrogel erosion rates in vivo and in vitro correlated, enabling the prediction of in vivo erosion of new material formulations from in vitro data. Collagen in vivo erosion was used to infer physiologic in vitro conditions that mimic erosive in vivo environments. This approach enables rapid in vitro screening of materials, and can be extended to simultaneously determine drug release and material erosion from a drug-eluting scaffold, or cell viability and material fate in tissue-engineering formulations.Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms 3,10,11,12,13 . Chromatography tracks molecular weight changes 2,12 but cannot be applied to eliminable materials that do not undergo chain scission. Material environment affects erosion, and the material and degradation products may affect the environment in turn 14,15 . Thus, in vivo residence times and in vitro durability of three dimensional degradable structures differ 2 . HHS Public AccessWe developed a noninvasive imaging technique that tracks material erosion in vivo through a fluorescent tag covalently attached to components of model materials. Materials erosion was calculated from the decay in total material fluorescence signal using non-invasive In Vivo Imaging System (IVIS). Model hydrolytically degradable adhesive materials used herein are based on polyethylene glycol (PEG) amine and dextran aldehyde 16,17 . PEG replete with amine groups and oxidized dextran react at body temperature in a Schiff base reaction to form adhesive materials as aldehydes bind to tissue amines. The reaction is reversible and the material hydrolyzes to its polymeric components 16,17 . Although PEG polymers may undergo enzymatic degradation, significant fluid uptake and swelling dominate the degradation of our formulated PEG:dextran hydrogels, resulting in hydrolyticsensitive materials. As material shape dictates fluid uptake, we examined whether fluorescence tracking could distinguish the fate of PEG:dextran formulations cast in a series of shapes, sizes and varied PEG solid content. Compressed denatured type II collagen was used as a model for enzymatically degradable material whose erosion profile should change with implantation site and natural variation in enzyme content.To enable the use of tagged materials to ...

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

“…Studies of interactions between immune cells and ECM‐based scaffolds may provide important mechanistic insight, but translating these materials into the clinic ultimately requires analysis of response in vivo. Furthermore, local environments have a profound effect on cellular behavior, often causing discrepancies between in vitro and in vivo data . For example, pro‐healing effects of MDP hydrogels were observed in implant studies in vivo, which were unexpected based on in vitro observations of minimal enhancement of cell viability, adhesion, and morphology compared to MDPs engineered with ECM‐derived peptides .…”