Incorporating nanocrystalline cellulose into a multifunctional hydrogel for heart valve tissue engineering applications

Abstract

Functional tissue engineered heart valves (TEHV) have been an elusive goal for nearly 30 years. Among the persistent challenges are the requirements for engineered valve leaflets that possess nonlinear elastic tissue biomechanical properties, support quiescent fibroblast phenotype, and resist osteogenic differentiation. Nanocellulose is an attractive tunable biological material that has not been employed to this application.In this study, we fabricated a series of photocrosslinkable composite hydrogels mNCC-MeGel (mNG) by conjugating TEMPO-modified nanocrystalline cellulose (mNCC) onto the backbone of methacrylated gelatin (MeGel). Their structures were characterized by FTIR, 1 HNMR and uniaxial compression testing. Human adiposederived mesenchymal stem cells (HADMSC) were encapsulated within the material and evaluated for valve interstitial cell phenotypes over 14 days culture in both normal and osteogenic media. Compared to the MeGel control group, the HADMSC encapsulated within mNG showed decreased alpha smooth muscle actin (αSMA) expression and increased vimentin and aggrecan expression, suggesting the material supports a quiescent fibroblastic phenotype. Under osteogenic media conditions, HADMSC within mNG hydrogels showed lower expression of osteogenic genes, including Runx2 and osteocalcin, indicating resistance toward calcification. As a proof of principle, the mNG hydrogel, combined with a viscosity enhancing agent, was used to 3D bioprint a tall, self-standing tubular structure that sustained cell viability.Together, these results identify mNG as an attractive biomaterial for TEHV applications.

Bacterial Cellulose-Based Blends and Composites: Versatile Biomaterials for Tissue Engineering Applications

“…Thanks to its nanofibrillar network, BC can connect with a variety of polymers to form nanocomposites that possess desirable characteristics and processable qualities pertaining to the demands of cardiovascular TE [ 160 ]. Ma et al [ 164 ] fabricated a chain of photocrosslinkable composite hydrogels mNCC-MeGel (mNG) by conjugating TEMPO-modified nanocrystalline cellulose (mNCC) onto the backbone of methacrylated gelatin (MeGel). The mNCC-MeGel (mNG) nanocomposite displayed enhanced mechanical properties.…”

Conductive and Semiconductive Nanocomposite‐Based Hydrogels for Cardiac Tissue Engineering

“…Therefore, this study demonstrated the efficiency of synthesized composite hydrogels for engineered multilayer heart valve engineering. [ 77 ]…”

“…Therefore, this study demonstrated the efficiency of synthesized composite hydrogels for engineered multilayer heart valve engineering. [77] In another study, Hinderer et al created an electrospinning scaffold consisting of PLA and PEGdma that was compatible with the structure and mechanical properties of the native valve matrix. They introduced important structural valves of the heart valve (collagen type I and Versicane) to the scaffold.…”

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

“…232 Interestingly, photocrosslinkable hydrogels constructed using GelMA and nanocellulose have exhibited non-linear biomechanics, suppressed osteo-induction, and improved quiescent fibroblast phenotype for the engineering of heart valves. 233…”