One‐Step Labeling of Collagen Hydrogels with Polydopamine and Manganese Porphyrin for Non‐Invasive Scaffold Tracking on Magnetic Resonance Imaging

Abstract

Biomaterial scaffolds are the cornerstone to supporting 3D tissue growth. Optimized scaffold design is critical to successful regeneration, and this optimization requires accurate knowledge of the scaffold's interaction with living tissue in the dynamic in vivo milieu. Unfortunately, non‐invasive methods that can probe scaffolds in the intact living subject are largely underexplored, with imaging‐based assessment relying on either imaging cells seeded on the scaffold or imaging scaffolds that have been chemically altered. In this work, the authors develop a broadly applicable magnetic resonance imaging (MRI) method to image scaffolds directly. A positive‐contrast “bright” manganese porphyrin (MnP) agent for labeling scaffolds is used to achieve high sensitivity and specificity, and polydopamine, a biologically derived universal adhesive, is employed for adhering the MnP. The technique was optimized in vitro on a prototypic collagen gel, and in vivo assessment was performed in rats. The results demonstrate superior in vivo scaffold visualization and the potential for quantitative tracking of degradation over time. Designed with ease of synthesis in mind and general applicability for the continuing expansion of available biomaterials, the proposed method will allow tissue engineers to assess and fine‐tune the in vivo behavior of their scaffolds for optimal regeneration.

In Vivo Imaging of Composite Hydrogel Scaffold Degradation Using CEST MRI and Two‐Color NIR Imaging

“…Hence, developing non‐invasive means for monitoring hydrogel degradation is highly desirable to further optimize scaffolded cell therapy . Hydrogels and other composite scaffolds have previously been labeled with near‐infrared (NIR) fluorescent dyes, carbon nanodots, radiopaque X‐ray contrast agents, 1 H MRI contrast agents, or perfluorocarbon 19 F MRI tracers11e,12 in order to detect their location and immediate dispersion. However, these labels cannot report directly on hydrogel biodegradation and would also need additional regulatory clearance for clinical use.…”

Ultrasmall Superparamagnetic Iron Oxide Labeled Silk Fibroin/Hydroxyapatite Multifunctional Scaffold Loaded With Bone Marrow-Derived Mesenchymal Stem Cells for Bone Regeneration

“…Wang et al utilized CT to noninvasively dynamic monitor biodegradable polymers regarding the microstructure of tissue engineering constructs labeled with gold nanoclusters (Wang et al, 2020). Recent image-guided tissue engineered approaches highlight the superiority of MRI for providing functional information about the biological response of implanted material (Hartman et al, 2002;Szulc and Cheng, 2019). Nevertheless, only few MRI studies have focused on in vivo imaging of musculoskeletal tissue implants longitudinally.…”

MRI method for labeling and imaging decellularized extracellular matrix scaffolds for tissue engineering

“…To label the dECM bladder scaffolds with MnPNH 2 a published protocol using a bio-inspired adhesive, polydo pamine (PDA), was used and modified. 11 The scaffolds were first immersed in either PBS (1×; pH 7.4) or Tris-HCl (10 mM; pH 9.6) before addition of dopamine hydrochloride (0, 0.1, 1.0, 5.0 mg/mL) for 24 h at room temperature with shaking. The scaffolds were then rinsed with PBS (1×; pH 7.4) and incubated with MnPNH 2 (0.4 mM or 4 mM) in PBS (1×; pH 7.4) at 37°C overnight with shaking.…”

“…A positive‐contrast manganese porphyrin (MnPNH 2 ) contrast agent is exploited for its efficient contrast enhancement and thermodynamic and kinetic stability, the latter being an especially key safety consideration. Similar to the method described by Szulc and Cheng for collagen hydrogels, the synthesis and labeling methods presented herein are facile and represent a flexible platform for further refinement and modification. We present the feasibility of our approach for labeling and imaging a range of decellularized tissue types currently investigated for regeneration using the dECM approach, including the bladder, lungs, and tracheal smooth muscle and cartilage.…”

“…A second scenario is when an entire decellularized organ is implanted, in which case labeling the implant would serve not to enable visualization (standard MR imaging suffices) but to permit monitoring of scaffold structure and content as it gets modified and degraded during integration. Whether we aim to replace part of or an entire organ, a potentially useful approach for labeling dECM material is one taken to label biomaterial gels with imaging contrast agents, with recent examples described for imaging collagen gels 11,12 and gel atin hydrogels 13 on MRI. To date, a method to label and vi sualize dECM scaffolds noninvasively on MRI has not been investigated.…”