Cell-Imprinted Substrates Act as an Artificial Niche for Skin Regeneration

Abstract

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications.

Cell-Imprinted Substrates Modulate Differentiation, Redifferentiation, and Transdifferentiation

“…This nano-imprinted topography derived from natural chondrocyte shapes acts as a shape cue and physical confining driving force which stimulates differentiation of stem cells to chondrocytes. The same results 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 were obtained from cell-imprinted substrates as morphological templates based on mature human keratinocyte 20 . The data acquired from atomic force microscopy and field emission scanning electron microscopy revealed that the chondrocyte (or keratinocyte)-cell-imprinted PDMS casting procedure could imitate the surface morphology of the plasma membrane, at typical dimensions ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation.…”

“…After 3 h, 1 ml culture medium was added to cover the cells and incubation maintained for 2 weeks with medium exchange every 4 days. Gene expression analysis and immuno-staining were conducted in the same way as previously published 20 . Tables 1 and 2 show the list of primer sequences and antibodies, respectively.…”

Topology of internally constrained polymer chains

“…The chain is in its native state and fully folded when all native contacts are formed. The permutation in the connectivity is done using the Heap algorithm 17 to ensure all conformations are surveyed and this is done for all 5 Â 10 6 conformations with different topological arrangements. This is verified through obtaining equal values in each topological state.…”

“…We use a coarse-grained model of a linear self-avoiding polymer chain 17,18 to investigate how the topological states of the intrachain contacts are affected as the external molecule (chaperone) changes the chain's global topology. This is carried out by simulation setups in which the chaperone keeps the chain termini at a certain distance.…”

Nanomaterials, Scaffolds, and Skin Tissue Regeneration

“…Recently biomimetic materials for skin regeneration were fabricated through cell-imprinting during which mature human keratinocyte morphological templates 12.1 Biomaterials for Scaffolds and Skin Tissue were used [ 14 ]. The keratinocyte-imprinted polymeric nanostructure, prepared by casting, imitated very well the surface morphology of the plasma membrane.…”