Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice

Abstract

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

“…cartilage, myocardium) [1][2] has significantly progressed in the past years starting by choosing a suitable biomaterial and competent cell source. Nevertheless, it is essential to control the process of angiogenesis and host response at the recipient site to ensure the functionality and survival of the engineered graft [3,4]. In this regard, many aspects need to be controlled according to specific purposes.…”

“…In this regard, many aspects need to be controlled according to specific purposes. For instance, the material degradation-rate needs to fit the envisioned application, allowing the desired ingrowth of host cells and extracellular matrix deposition (ECM) [3]. Furthermore, the prompt in vivo induction of angiogenesis is often mandatory (e.g.…”

In Vivo Examination of an Injectable Hydrogel System Crosslinked by Peptide–Oligosaccharide Interaction in Immunocompetent Nude Mice

“…Another very important aspect for developing injectable biomaterials is to monitor the biomaterial with methods compatible with clinical practice. Whereas histological and biochemical analyses can illustrate the interaction between biomaterials and host tissue, characterization with high‐resolution in vivo imaging technique such as computed tomography (µ‐CT), magnetic resonance imaging (MRI), and optical imaging, e.g., infrared (IR) fluorescence imaging, can provide information regarding the biomaterial in vivo noninvasively. Such analyses could be particularly interesting for long‐term monitoring, in which the native tissue and artificial material interact with each other over a period of weeks to months.…”

An orthotopic xenograft model for high-risk non-muscle invasive bladder cancer in mice: influence of mouse strain, tumor cell count, dwell time and bladder pretreatment

“…Multimodal imaging of tumor growth (BLI, MRI) and functional characteristics (PET) was performed as published elsewhere [ 21 – 24 ]. In brief, BLI (exposure times 1 s, 10 s, and 60 s) of anesthetized mice in prone position was performed using a dedicated small animal multimodal imaging system (In-Vivo Xtreme) 10–12 min after intraperitoneal injection of 200 μl of D-luciferin (15 mg/ml).…”