A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy

Abstract

Cryo-hydrogels (cryogels) are polymer hydrogels formed at sub-zero temperatures. Bioscaffolds created from cryo-gels have interconnected macropores which allow for cell migration, tissue-ingrowth, unhindered diffusion of solutes and mass transport of therapeutics. In this study, we developed collagen based cryogel bioscaffolds and coated them with polydopamine using a simple two-step technique. Cryogel bioscaffolds were synthesized by collagen crosslinking at −20°C and exhibited a macroporous interconnected architecture with 75% ± 63% porosity. Two groups of pore sizes were observed: 300 ± 50 μm and 30 ± 10 μm in diameter. The addition of a polydopamine coating to cryogel bioscaffolds was confirmed using composition analysis. This resulted in a 41% ± 6 5% decrease in water uptake, 81% ± 10% decrease in swelling rate and 12% ± 3% decrease in their degree of dissolution (p < 0.05), with a 48% ± 2% increase in stiffness and 57% ± 5% increase in compressive strength (p < 0.05). Seeding adipose tissue-derived mesenchymal stem cells (AD-MSCs) into polydopamine coated-cryogel bioscaffolds resulted in cells demonstrating a 52% ± 4% increase in viability and 33% ±3% increase in proliferation when compared to ADMSCs seeded into uncoated-cryogel bioscaffolds (p < 0.05). In summary, our novel polydopamine coated-cryogel bioscaffold represents an efficient and low-cost bioscaffold platform to support MSC therapies.

Three‐dimensional cryogels for biomedical applications

“…It was also discovered that stem cells freshly isolated from cord blood and immediately seeded into cryogel bioscaffolds produced the best properties of cell adhesion, proliferation, differentiation, and survival (Jurga et al, ) compared with stem cells isolated at later differentiation and maturation time‐points. In addition, polydopamine‐coated collagen cryogels were also found to increase adipose‐derived MSC viability by 52% ± 4% and proliferation by 33% ± 3% compared with growth on control uncoated collagen cryogels (Razavi et al, ).…”

“…These collagen cryogels demonstrate high porosity and an interconnected bimodally-distributed (microporous and macroporous) architecture that behaves like a sponge, allowing for mass transport and control over cellular mechanisms. In addition, collagen-based cryogels have also been synthesized for applications of stem cell therapy Razavi et al, 2018, with studies showing human osteoblast-like cells being able to attach and spread along both homopolymeric collagen and heteropolymeric composite bioscaffolds (Rodrigues et al, 2013).…”

“…Cryogels can be coated with different molecules and biological factors to provide a suitable microenvironment for cell growth and maintenance in different bioengineering applications. Coating of cryogels can also affect the viability and proliferation potential of matrix-seeded cells (Razavi et al, 2018). For the controlled release of growth factors from cryogels, several biomaterial moieties can also be functionalized on cryogels (Raina et al, 2016) which are explained in this section.…”

“…Coating of cryogels can affect the viability and proliferation potential of matrix-seeded mesenchymal stem cells (MSCs). For example, Razavi et al (2018) previously showed the effects of polydopamine coating on collagen cryogels, and found that adipose-derived MSCs demonstrated an increase in viability and proliferation when grown on coated cryogels compared with control uncoated collagen cryogels. Additionally, the process of polydopamine coating is unique in that polydopamine is both pHand light-sensitive, so immersion of bioscaffolds in dopamine solution was required to be performed in the dark at pH 8.5 (Figure 4).…”

“…I G U R E 4 (a) Photographs, μ-CT, SEM images of an uncoated-and polydopamine coated-cryogel bioscaffold: In μ-CT images, the purple areas show the bioscaffold material and the dark areas refer to the void space, SEM images showing the existence of both small, large, and continuously interconnected macropores throughout the entire bioscaffold construct; (b) SEM images of AD-MSCs (indicated by white arrows) on the superficial layer and within the center of uncoated-and polydopamine coated-cryogel bioscaffolds at Day 10; (c) confocal images of AD-MSCs after 1 and 10 days seeding into uncoated-and polydopamine coated-cryogel bioscaffolds (direct contact) and culturing with the medium of uncoated-and polydopamine coated-cryogel bioscaffolds (indirect contact) and the results of AD-MSCs counting at Day 0, 1, and 10 showing the improved AD-MSCs proliferation when cryogel bioscaffolds were coated with polydopamine (reproduced with permission fromRazavi, M., Hu, S., & Thakor, A. S. (2018). A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy.…”