Abstract
Biodegradable scaffolds have a major therapeutic advantage in regenerative medicine with their ability to include multiple compounds of drugs, growth factors and more recently, stem cells within the matrix. The scaffold can be programmed with mechanoresistive parameters targeted to the tissue to be replaced. Direct chemoattraction of in vivo stem cells to the implanted scaffold would be advantageous in the clinical setting. Large peptides such as vasculo-endothelial growth factor have demonstrated chemotaxis for angiogenesis from endothelial cells. This suggests other endogenous peptides may be present to directly attract stem cells to a scaffold. This exploratory study assessed if peptides from the blood peptidome would display chemotaxis to stem cells. Results showed that several short N-mer peptides demonstrated remarkable chemotaxis to blood and adipose tissue derived stem cells. Sodium alginate hydrogel was placed into 6-well, 24-well plate, and partitioned plates with channels between the wells. Connected wells were in series and spiked with peptides, biofluids containing stem cells and control wells. Images were recorded between three and nine days after incubation at 37°C. There were rapid migration and expansion of stem cells into the peptide wells. Cell analysis revealed activated stem cells on a number of parameters including autophagy, Ki67 and nitric oxide. Potentially, this enhanced method to bioscaffold design utilizing peptide chemoattraction could result in an improved approach for stem cell therapy and regenerative medicine applications. Specific patient groups (e.g. blood coagulation disorders) where surgery to acquire adipose tissue or bone marrow is contraindicated may benefit. In addition, the technology is portable and safe by using “on demand” peripheral blood derived stem cells and would be particularly suitable for specialized environments such as space medicine.
Highlights
Comprehensive tissue engineering encompasses diverse and developing fields that include biological scaffolds, drug delivery systems, nanoengineering and optimizing the extracellular matrix for cell signaling
Cell analysis and cytometry on the non-crosslinked hydrogel in this study showed cell health was maintained in the migration and expansion of both adipose derived stem cells (ADSCs) and hematopoietic stem cells (HSCs)
At the molecular and cellular level immune cells undergo rapid chemotaxis and migration to noxious by-products expressed by pathogens
Summary
Comprehensive tissue engineering encompasses diverse and developing fields that include biological scaffolds, drug delivery systems, nanoengineering and optimizing the extracellular matrix for cell signaling. An area of great interest has been seeding of the scaffold to enhance various mechanistic aspects of the framework for stem cell differentiation. Biodegradable microneedles have been explored for transdermal drug delivery systems with the outer coating and needle point comprised of natural compound materials such as crystalline hyaluronic acid, with the inner chamber housing the therapeutic drug [3]. One further novel concept has been impregnating a biodegradable 3D printed outer polylactic-glycolic acid shell enveloping a gel housing mesenchymal stem cells, for skin regeneration [4]. The researchers commented that the approach can only contain a minimal number of stem cells
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