Evaluation of Fibrin-Based Interpenetrating Polymer Networks as Potential Biomaterials for Tissue Engineering

Abstract

Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts. We further evaluated their biocompatibility ex vivo with a chick embryo organotypic culture model. Subcutaneous implantations of the matrices were subsequently conducted on nude mice to investigate their biocompatibility in vivo. Our preliminary data highlighted that our biomaterials were non-cytotoxic (viability above 90%). The organotypic culture showed that the IPN matrices induced higher cell adhesion (across all the explanted organ tissues) and migration (skin, intestine) than the control groups, suggesting the advantages of using a biomimetic, yet mechanically-reinforced IPN-based matrix. We observed no major inflammatory response up to 12 weeks post implantation. All together, these data suggest that these fibrin-based IPNs are promising biomaterials for tissue engineering.

Polysaccharide-Based Bioink Formulation for 3D Bioprinting of an In Vitro Model of the Human Dermis

“…A proof of the suitability of the prepared model of the dermis through 3D printing of the developed bioink formulation, are the patches of the keratinocyte (epidermal layer) that formed on the surface of the base bioprinted dermal construct (see Supplementary Materials, Figure S4). However, to confirm bioactive features of our dermal construct to attract and retain a large number of keratinocytes, some additional cell adhesion assessment on hSF-laden should be performed by using, for example, an arbitrary index inversely proportional to the cell detachment kinetics [67]. Furthermore, scanning electron microscopy (SEM) was performed in order to indirectly evaluate the interaction between the keratinocytes attached to the scaffold surface.…”

Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

“…This phase‐separated structure allows to obtain a bulking agent (e.g., for bladder) that takes advantages of collagen mechanical properties and of the facility of fibrin molecular engineering (in these cases fibrin was functionalized with a fusion protein containing IGF‐1, an MMP‐cleavable bridge and a Factor XIII substrate). Interpenetrating networks . “Ideal” IPNs should be co‐continuous networks of, for example, fibrin and another component; their composition should be roughly homogeneous at any level of scale, that is, taking molecule A and molecule B at a given composition, the same A/B ratio should be found at a macroscopic, microscopic or nanoscopic scale (Figure C, left). In real cases, IPNs may have a degree of phase separation (Figure C, middle), and this may extend to the point of one component being segregated in isolated domains (Figure C, right) .…”

“…Interpenetrating networks . “Ideal” IPNs should be co‐continuous networks of, for example, fibrin and another component; their composition should be roughly homogeneous at any level of scale, that is, taking molecule A and molecule B at a given composition, the same A/B ratio should be found at a macroscopic, microscopic or nanoscopic scale (Figure C, left). In real cases, IPNs may have a degree of phase separation (Figure C, middle), and this may extend to the point of one component being segregated in isolated domains (Figure C, right) .…”

Gelatin interpenetration in poly N‐isopropylacrylamide network reduces the compressive modulus of the scaffold: A property employed to mimic hepatic matrix stiffness

“…Using such a combination allows obtaining biocompatibility and proffer tunability to other physicochemical properties (Jain et al, ). One such instance is utilization of interpenetrating polymer networks that have been widely used to improve the mechanical strength of scaffolds for various tissue engineering applications, for example skin, bone, cartilage, and so forth (Chung et al, ; Gsib et al, ; Rennerfeldt et al, ; Van Vlierberghe et al, ). The stiffness of normal liver ranges from approximately 0.6 to 2 kPa, and could increase to approximately 20 kPa in a diseased state like cirrhosis (Yeh et al, ).…”