Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery

Zhang, Yu; Sun, Yi; Xia, Yang; Hilborn, Jöns; Heerschap, Arend; Ossipov, Dmitri

doi:10.1002/mabi.201400117

Cited by 52 publications

(39 citation statements)

References 24 publications

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“…Similarly, iron oxide nanoparticles have been incorporated into HA hydrogels as magnetic resonance imaging (MRI) contrast agents. Ossipov and co-workers [82] have developed multifunctional HA hydrogels composed of iron oxide nanoparticle hybridized HA nanogels utilizing a chemoselective hydrazone coupling reaction. Upon the enzymatic degradation of hydrogels by hyaluronidase, the release of nanogels led to a decrease in the concentration of iron oxide nanoparticles within the matrix, which allows the real-time monitoring of hydrogel degradation via MRI.…”

Section: Microstructured Gag Gels Nanoparticle-containing Gag Gelmentioning

confidence: 99%

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

et al. 2016

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Glycosaminoglycans (GAGs) govern important functional characteristics of the extracellular matrix (ECM) in living tissues. Incorporation of GAGs into biomaterials opens up new routes for the presentation of signaling molecules, providing control over development, homeostasis, inflammation and tumor formation and progression. This review discusses recent approaches to GAG-based materials, highlighting the formation of modular, tunable biohybrid hydrogels by covalent and non-covalent conjugation schemes, including both theory-driven design concepts and advanced processing technologies. Examples of the application of the resulting materials in biomedical studies are provided. For perspective, we highlight solid-phase and chemoenzymatic oligosaccharide synthesis methods for GAG-derived motifs, rational and high-throughput design strategies for GAG-based materials and the utilization of the factor-scavenging characteristics of GAGs.

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Section: Microstructured Gag Gels Nanoparticle-containing Gag Gelmentioning

confidence: 99%

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

et al. 2016

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“…Other groups have shown similar iron oxide nanoparticulate composite polymers, but, as many of these are designed for hyperthermic drug delivery and often involve bulk polymerization or more rapidly hydrolyzed materials, the potential lifetime of an iron-included polymeric microdevice utilizing covalent incorporation remains unclear. 42−44 Furthermore, due to the discretized nature of our low concentration microstructured composites and the use of slow-acting permanent magnetic fields, we have not seen evidence of environmental damage or heating due to the motion of the microrods. This includes no observed temperature change in a Matrigel culture loaded with magnetic microrods and exposed to a high frequency oscillating electromagnetic field (data not shown) and no evidence of microstructure translocation or structural damage to a gel scaffold in the presence of strong magnetic fields over long incubation periods of 4–15 h (Figure 4).…”

Section: Discussionmentioning

confidence: 92%

Novel Functionalization of Discrete Polymeric Biomaterial Microstructures for Applications in Imaging and Three-Dimensional Manipulation

Pinney

Melkus

Cerchiari

et al. 2014

ACS Appl. Mater. Interfaces

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Adapting ways to functionalize polymer materials is becoming increasingly important to their implementation in translational biomedical sciences. By tuning the mechanical, chemical, and biological qualities of these materials, their applications can be broadened, opening the door for more advanced integration into modern medical techniques. Here, we report on a method to integrate chemical functionalizations into discrete, microscale polymer structures, which are used for tissue engineering applications, for in vivo localization, and three-dimensional manipulation. Iron oxide nanoparticles were incorporated into the polymer matrix using common photolithographic techniques to create stably functional microstructures with magnetic potential. Using magnetic resonance imaging (MRI), we can promote visualization of microstructures contained in small collections, as well as facilitate the manipulation and alignment of microtopographical cues in a realistic tissue environment. Using similar polymer functionalization techniques, fluorine-containing compounds were also embedded in the polymer matrix of photolithographically fabricated microstructures. The incorporation of fluorine-containing compounds enabled highly sensitive and specific detection of microstructures in physiologic settings using fluorine MRI techniques (19F MRI). These functionalization strategies will facilitate more reliable noninvasive tracking and characterization of microstructured polymer implants as well as have implications for remote microstructural scaffolding alignment for three-dimensional tissue engineering applications.

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“…However, many scaffolding materials are designed to biodegrade, as host cells invade the material and gradually replace it [10], hence becoming indistinguishable from host tissue. In these cases, MR contrast agents can be integrated into, for instance, hyaluronic acid (HA)-based hydrogels, to afford a specific visualization of their location and degradation [18, 19]. …”

Section: Introductionmentioning

confidence: 99%

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

et al. 2017

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Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity. In vitro imaging indicated a robust concentration-dependent detection of the ECM precursor and hydrogel at 1.8 and 3.6 ppm, which broadly corresponded to chondroitin sulfate and fibronectin. This detection was robust to changes in pH and improved at 37 °C. In vivo implantation of ECM hydrogel into the stroke cavity in a rat model corresponded macroscopically to the distribution of biomaterial as indicated by histology, but mismatches were also evident. Indeed, CEST imaging detected an endogenous “increased deposition”. To account for this endogenous activity, pre-implantation images were subtracted from post-implantation images to yield a selective visualization of hydrogel distribution in the stroke cavity and its evolution over 7 days. The CEST detection of ECM returned to baseline within 3 days due to a decrease in fibronectin and chondroitin sulfate in the hydrogel. The distribution of ECM hydrogel within the stroke cavity is hence feasible in vivo, but further advances are required to warrant a selective long-term monitoring in the context of biodegradation.

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Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery

Cited by 52 publications

References 24 publications

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

Novel Functionalization of Discrete Polymeric Biomaterial Microstructures for Applications in Imaging and Three-Dimensional Manipulation

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

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