Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Abstract

Therapies that promote angiogenesis have been successfully applied using various combinations of proangiogenic factors together with a biodegradable delivery vehicle. In this study we used bimodal noninvasive monitoring to show that the host response to a proangiogenic biomaterial can be drastically affected by the mode of implantation and the surface area-to-volume ratio of the implant material. Fluorescence/MRI probes were covalently conjugated to VEGF-bearing biodegradable PEG-fibrinogen hydrogel implants and used to document the in vivo degradation and liberation of bioactive constituents in an s.c. rat implantation model. The hydrogel biodegradation and angiogenic host response with three types of VEGFbearing implant configurations were compared: preformed cylindrical plugs, preformed injectable microbeads, and hydrogel precursor, injected and polymerized in situ. Although all three were made with identical amounts of precursor constituents, the MRI data revealed that in situ polymerized hydrogels were fully degraded within 2 wk; microbead degradation was more moderate, and plugs degraded significantly more slowly than the other configurations. The presence of hydrogel degradation products containing the fluorescent label in the surrounding tissues revealed a distinct biphasic release profile for each type of implant configuration. The purported in vivo VEGF release profile from the microbeads resulted in highly vascularized s.c. tissue containing up to 16-fold more capillaries in comparison with controls. These findings demonstrate that the configuration of an implant can play an important role not only in the degradation and resorption properties of the materials, but also in consequent host angiogenic response.biomaterial scaffold | angiogenesis | hydrogel | contrast agents | tissue regeneration W ith progress in the field of regenerative medicine relying more on approaches that deliver cells and/or bioactive factors using minimally invasive procedures, functional donor-tohost integration remains a critical challenge. In this context, biodegradable hydrogel scaffolds provide certain advantages, such as excellent tissue compatibility, temporary protection from host inflammation, and controlled resorption based on cell-mediated degradation (1). Effective transport properties to and within an implanted hydrogel are critical in the design of cell-seeded scaffolds, where the delivery of nutrients and removal of waste products from regions deep within the implant can severely limit the use of a patch for only the smallest of grafts (i.e., <0.5 mm) (2-4). Therefore, a great deal of research in the field of regenerative medicine has been devoted to ameliorate the survival of the cells and tissues with implants that use proangiogenic factors.One strategy is to enhance the localized formation of vascularized networks to improve the perfusion of oxygen and nutrients to the intended region in the body (2, 4, 5). This process is regulated by a number of different growth factors that stimulate a complex angiogenic res...

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“…15 Recently, Heo et al developed fluorescencebased in vivo glucose sensing system, where they synthesized a glucose-response fluorescent microfibers with blue light emission for real-time intensity tracking via subcutaneous mouse model. 13 Besides biosensing applications, noninvasive fluorescence imaging has been extensively used for in vivo degradation tracking of the injected or implanted materials.…”

Biocompatibility of Pegylated Fibrinogen and Its Effect on Healing of Full-Thickness Skin Defects: A Preliminary Study in Rats

“…The gel precursor solution spread out in the wound quickly and homogenously and integrated in the whole wound area; an advantage that has been reported accordingly [33]. After 5 minutes exposure to UV light, the hydrogel polymerized with consistency of elastic gels as previously reported [21].…”

“…The surface erosion of the bulk implant started at day 8 [32]. The model, where the hydrogel was polymerized in situ, showed a complete disassembly of the PEGfibrinogen within 2 weeks, with an average of 90% material dissolved during the first week [33]. The rate of the PEG-fibrinogen degradation is highly dependent on the implantation site and the composition of the implant material.…”

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“…Additionally, the fibrinogen affords the scaffold proteolytic sensitivity for in situ biodegradation by cell activated protease activity [31]. It has been shown, that PEG-fibrinogen is degraded in vivo by surface erosion, with a remarkably low foreign body response [32,33].…”