Self‐Folding 3D Silk Biomaterial Rolls to Facilitate Axon and Bone Regeneration

Abstract

Biomaterial scaffold designs are needed for self‐organizing features related to tissue formation while also simplifying the fabrication processes involved. Toward this goal, silk protein‐based self‐folding scaffolds to support 3D cell culture, while providing directional guidance and promotion of cell growth and differentiation, are reported. A simple and robust one‐step self‐folding approach is developed using bilayers consisting of a hydrogel and silk film in aqueous solution. The 3D silk rolls, with patterns transferred from the initially prepared 2D films, guide the directional outgrowth of neurites and also promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). The osteogenic outcomes are further supported by enhanced biomechanical performance. By utilizing this self‐folding method, cocultures of neurons and hMSCs are achieved by patterning cells on silk films and then converting these materials into a 3D format with rolling, mimicking aspects of the structure of osteons and providing physiologically relevant structures to promote bone regeneration. These results demonstrate the utility of self‐folded silk rolls as efficient scaffold systems for tissue regeneration, while exploiting relatively simple 2D designs programmed to form more complex 3D structures.

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

“…Silk fibroins in combination with HA nanocomposite particles can be adjusted to facilitate the formation of different bone types or required regeneration period [ 80 ]. Alternatively silk fibroins have been manipulated in vitro to form biomaterial rolls resembling the appearance of osteons, which enabled not only osteogenesis of human MSC (hMSC) but also the survival and directional growth of neurite processes [ 81 ]. Other examples include the development of bioglass functionalized gelatin nanofibrous scaffolds, which promoted ectopic bone formation in rats [ 64 ], and the use of the BMSC derived extracellular matrix in combination with a 3D-printed HA scaffold to promote strong osteogenic ability and appropriate “tissue-space” structure [ 82 ].…”

Photoacoustic Carbon Nanotubes Embedded Silk Scaffolds for Neural Stimulation and Regeneration

“…To prepare the CNT/silk scaffolds, 20-100 µg/mL of functionalized CNT solution was mixed with 2% (w/v) silk fibroin solution to obtain the solution for casting. The CNT/Silk scaffolds were then prepared through a cast-and-dry method (Figure 1a) to form films with a typical thickness of 32.54 ± 1.98 µm (Figure . S2a) or a 3D roll structure (Figure S2b) through the self-folding strategy we have previously reported [21] . All CNT/silk films used in following experiments were fabricated from solutions of 20 ug/mL functionalized CNT and 2% (w/v) silk fibroin, unless otherwise specified.…”

Four-Dimensional (Bio-)printing: A Review on Stimuli-Responsive Mechanisms and Their Biomedical Suitability

“…After being stimulated with temperature, the components in the droplets can be released [24]. Other macroscale materials with self-morphing [202], and self-folding properties have shown promise in tissue regeneration [203][204][205].…”