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

Artzi, Natalie; Oliva, Nuria; Puron, Cristina; Shitreet, Sagi; Artzi, Shay; Ramos, Adriana Bon; Groothuis, Adam; Sahagian, G. Gary; Edelman, Elazer R.

doi:10.1038/nmat3095

Cited by 193 publications

(185 citation statements)

References 25 publications

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“…These results are consistent with previous studies that use other techniques to document how in vivo fate of biomaterial implants is dependent on the composition, dimensions, in situ environment, and degradation products (13,15,(26)(27)(28). In the context of hydrogel biomaterial implants specifically, the MRI results are in close agreement with the work of Artzi et al (15); they also showed that implant geometry significantly affects the in vivo degradation patterns of the implant. Using block and mesh cylinders made with differing surface area-tovolume ratios, they demonstrated that bulky disk-shaped implants were much slower to be resorbed in situ.…”

Section: Significancesupporting

confidence: 91%

“…Although VEGF has been used exogenously to promote in vivo angiogenesis, superior results were obtained when the factor was protected, localized, and temporally controlled at the site of implantation (7,10,11). The hypothesis underlying this study is that degradation and resorption characteristics of the implant may be influenced by its surface area-to-volume ratio and mode of implantation, and hence the release properties of the proangiogenic factors within the implant site can be optimized accordingly (12)(13)(14)(15). As a case in point, an injectable strategy whereby the hydrogel precursor solution is injected and crosslinked in situ allows an even and contiguous dispersion of the hydrogel within the injury interstitial space for better host integration.…”

mentioning

confidence: 97%

“…With the optimization of a hydrogel scaffold requiring more information of the transient steps of integration, techniques to continuously monitor the degradation of a scaffold using fluorescence labeling have been described (15,19,20). However, in vivo fluorescence monitoring of biomaterials often results in a diffuse signal that does not allow for accurately determining the implant volume or its exact anatomical placement.…”

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confidence: 99%

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

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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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Section: Significancesupporting

confidence: 91%

mentioning

confidence: 97%

mentioning

confidence: 99%

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

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Other methods detect the released drug amount in blood samples, e.g., by HPLC [13] or radioactivity measurements of the labeled drug [14]. Recently, in vivo imaging techniques have become available that are able to track the in vivo behavior of fluorescently labeled substances and can be used for biodegradation and biodistribution studies [15][16]. In comparison to conventional in vivo studies, these imaging systems are advantageous because individual animals can be monitored over an extended period of time.…”

Section: Introductionmentioning

confidence: 99%

Comparison of in vitro and in vivo protein release from hydrogel systems

Wöhl-Bruhn

Badar

Bertz

et al. 2012

Journal of Controlled Release

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“…Intelligent hydrogel-based matrix designs would enable the programming of the nanoparticles´ release kinetics to occur in response to extrinsic factors such as light, temperature or pH. This can be combined with the ability to track the release using optical imaging, making these hydrogels ideal candidates for the local delivery of siRNAs [154][155][156].…”

Section: Route Of Administrationmentioning

confidence: 99%

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 2 inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. *Manuscript Click here to view linked References

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

Cited by 193 publications

References 25 publications

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

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

Comparison of in vitro and in vivo protein release from hydrogel systems

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

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