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

Abstract

The progression of liver disease from normal to cirrhotic state is characterized by modulation of the stiffness of the extracellular matrix (ECM). Mimicking this modulation in vitro scaffold could provide a better insight into hepatic cell behavior. In this study, interpenetrating poly(N‐isopropylacrylamide‐co‐gelatin) cryogels were synthesized in 48 different compositions to yield scaffolds of different properties. It was observed that a high concentration of N‐isopropylacrylamide (NIPAAm) leads to the formation of small pores while gelatin interpenetration on poly‐NIPAAm framework renders porous structure. Swelling properties and porosity of the gels decreased with an increase in NIPAAm concentration owing to the increased compactness of the gels. Gelatin interpenetration relaxed the gels and enhanced these properties. An increase in gelatin concentration led to a reduction in compressive moduli indicating that gelatin interpenetration in the poly‐NIPAAm network softens the cryogel. With the increase in NIPAAm concentration, the effect of gelatin interpenetration in reducing the compressive moduli expanded. The cytocompatibility studies indicated that the gels are cell‐adherent and compatible with HepG2. Furthermore, biochemical and real‐time polymerase chain reaction studies revealed that HepG2 and Huh‐7 cells cultured on scaffolds mimicking the ECM stiffness of normal liver (1.5–2.5 kPa) exhibited optimum liver‐specific functionalities. Increasing the stiffness to fibrotic (4–9 kPa) and cirrhotic (10–20 kPa) ECM decreases the functionality.

A bioartificial liver support system integrated with a DLM/GelMA-based bioengineered whole liver for prevention of hepatic encephalopathy via enhanced ammonia reduction

“…More importantly, 5% GelMA, once solidified within DLM, provides biologically relevant stiffness and biomechanical properties resembled to native liver ECM in vivo 33,34 . Studies have shown that the stiffness in ECM can promote stem cell differentiation 35 , maintain cell functionality 36 , and reverse aged oligodendrocyte progenitor cells 37 . With this physiologically relevant stiffness and mechanical support, hepatocytes can be well immobilized within DLM with good cell viability (more than 90%), cell engraftment and cell…”

Three dimensional polyvinyl alcohol scaffolds modified with collagen for HepG2 cell culture

“…Some domain in collagen (like Phe-Hyp-Gly unit) can act as ligands for the integrin family receptors of cell surface, and potentially activate specific biological signals to promote cell attachment and proliferation. 43 In this work, HepG2 cells were used to detect the biological performance of the PVA/COL (0.8%) and PVA scaffolds. The SEM images intuitively displayed the growth and distribution of cells on the scaffolds.…”

Construction of tissue-customized hydrogels from cross-linkable materials for effective tissue regeneration

“…8 For instance, poly(hydroxyethyl methacrylate) (PHEMA), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(ethylene glycol)-diacrylate (PEGDA), polycaprolactone (PCL), poly(acryl amide)/ poly(acrylic acid), gelatin methacryloyl (GelMA), poly(propylene fumarate) (PPF), poly(oligo ethylene glycol methacrylate) (POEGMA), and poly(N-isopropylacrylamide) (PNIPAM) are the typical synthesized materials that have been widely adopted to produce tissue-engineering hydrogels. 7,8,65,69,72,75,76,134,181 These synthetic materials are often modified macromers that present elongated degradation rates and make tissue engineering more tunable. 182,183 For example, thio-b ester-modified PEGDA hydrogels provide tunable degradation rates without changing the network of the PEGDA hydrogel.…”