Nanofibrous PLGA electrospun scaffolds modified with type I collagen influence hepatocyte function and support viability in vitro

Abstract

Culturing primary hepatocytes within a three-dimensional (3D) structure that mimics the natural liver environment is a promising strategy for extending the function and viability of hepatocytes in vitro. In the present study we generate porous PLGA nanofibers, that are chemically modified with extracellular matrix proteins, to serve as 3D scaffolds for the in vitro culture of primary human hepatocytes. Our findings demonstrate that the use of ECM proteins, especially type I collagen, in a porous 3D environment helps to improve the synthetic function of primary hepatocytes over time. We believe the work presented within will provide insights to readers for drug toxicity and tissue engineering applications.

Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques

“…However, hydrolysis is pH dependent and detrimental surface degradation may occur . Brown et al prepared nanofibrous PLGA electrospun scaffolds using the wet electrospinning technique . They hydrolyzed the surface of scaffolds by immersing in 0.01 m NaOH solutions.…”

“…They found that incorporation of collagen I on the surface of the PLGA nanofiber scaffolds resulted in higher hepatocyte‐specific gene expression, albumin secretion, and cytochrome P450 catalytic function in comparison with the scaffolds coupled to fibronectin and unmodified PLGA scaffolds. They concluded that cell‐laden collagen‐bonded PLGA nanofibrous scaffolds provided a specific microenvironment for long‐term in vitro survival and function of primary hepatocyte, which can be attributed to the presence of collagen I on the surface of nanofiber scaffolds …”

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

“…Moreover, the hepatic functions of the attached cells were not significantly changed. 106 Brown et al 107 modified a nanofibrous PLGA electrospun scaffold with a type I collagen coating. The modified scaffold led to 10-fold greater albumin secretion, 4-fold higher urea synthesis, and elevated transcription of hepatocyte-specific CYP450 genes in primary human hepatocytes compared to the unmodified PLGA scaffolds.…”

“…The modified scaffold led to 10-fold greater albumin secretion, 4-fold higher urea synthesis, and elevated transcription of hepatocyte-specific CYP450 genes in primary human hepatocytes compared to the unmodified PLGA scaffolds. 107 Similarly, Bierwolf et al 108 developed a collagen-coated PLLA electrospun nanofibrous scaffold which provide a good in vitro microenvironment for new tissue regeneration of primary rat hepatocytes. Application of novel materials for liver matrix scaffold construction and organogenesis were illustrated in Figure 3.…”

Structural Design, Fabrication and Evaluation of Resorbable Fiber-Based Tissue Engineering Scaffolds

“…Its widespread use is accredited to its ease of manipulation, cheap and accessible equipment needs, and its versatility. The technique can be applied to various materials, ranging from synthetic polymers such as PLA [103], PGA [104], PCL [105,106], PU [107,108], and their copolymers [109], to natural polymers such as collagen [110,111], elastin [112], gelatin [113] and chitosan [114]. Electrospun scaffolds have been applied in various tissue engineering applications, such as skin [115], bone [107,116], cartilage [113,117], tendon [118,119], ligament [118], nerve [105,120], blood vessel [121], cardiac tissue [122], and aortic valve [108].…”