Hydrogel skin substitute
Dr. Amini-Nik and colleagues have developed a cellularized bilayer pullulan-gelatin hydrogel to help regenerate the skin. They have performed in vivo experiments to demonstrate that cellularized pullulan-gelatin first generation hydrogel promotes skin regeneration and wound healing in wounds such as burns and chronic wounds7.
"We not only need proper material in the scaffold of a skin substitute which can provide a niche for stem cells to grow and differentiate, but also we need a technology to bring the stem cells together in a special formation which facilitates their growth and differentiation," Dr. Amini-Nik says.
The skin is a rich reservoir for stem cells from different lineages, with stem cells going through differentiation, regarded as a possible mechanism for the impact on wound healing, Dr. Amini-Nik explains.
Mesenchymal stem cells (MSCs) have been studied for their effect on wound healing. There are various sources of MSCs such as the bone marrow, adipose tissue, and the umbilical cord. Investigators have turned to the umbilical cord as a possible source of MSCs that would be preferable over bone marrow and adipose tissue because the umbilical cord stem cells offer a high yield and a lower level of immunogenicity.
The value of human Wharton's jelly-derived MSCs had not been extensively studied in human normal skin. An investigation using an in vivo mouse model demonstrated that human Wharton's jelly-derived MSCs and their secretome offered improved wound healing8.
"Once the right stem cells and the right scaffold is available, we need a technology that can assemble stem cells in spatial composition similar to the skin," Dr. Amini-Nik explains.
Biomedical engineering colleagues at the University of Toronto have developed a microfluidic device which allows controllable incorporation of material and cells within a flowing biopolymer sheet. Three-dimensional soft material assemblies are feasible with the technology9.
Using this technology and in collaboration with the biomedical engineering team, Dr. Amini-Nik and colleagues aimed to design a "skin printer" which allows for the formation of a skin substitute and can accommodate multiple stem cell populations in well-defined regions within the same skin substitute.
Dr. Amini-Nik is working with colleagues to determine the optimal combination of stem cells and scaffolding to produce layers of skin with the prototype design.
Disclosure: Dr. Amini-Nik reports no relevant disclosures.
1Brem H, Stojadinovic O, Diegelmann RF, et al. Molecular markers in Patients with Chronic Wounds to Guide Surgical Debridement. Mol Med. 2007;13(1-2):30-9.
2Amini-Nik S, Cambridge, E, Yu W, et al. beta-Catenin-regulated myeloid cell adhesion and migration determine wound healing. J Clin Invest. 2014; 124(6):2599-610.
3 Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci. 2013;70(12):2059-81.
4Jeschke MG, Patsouris D, Stanojcic M, et al. Pathophysiologic Response to Burns in the Elderly. EBioMedicine. 2015; 2(10):1536-48.
5Jeschke MG, Pinto R, Costford SR, Amini-Nik S. Threshold age and burn size associated with poor outcomes in the elderly after burn injury. Burns. 2016;42(2):276-81.
6Nicholas MN, Jeschke MG, Amini-Nik S. Methodologies in creating skin substitutes. Cell Mol Life Sci. 2016;73(18): 3453-72.
7Nicholas MN, Jeschke MG, Amini-Nik S. Cellularized Bilayer Pullulan- Gelatin Hydrogel for Skin Regeneration. Tissue Eng Part A. 2016;22(9- 10):754-64.
8Arno AI, Amini-Nik S, Blit PH, et al. Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling. Stem Cell Res Ther. 2014;5(1):28.
9Leng L, McAlister A, Zhang B, Radisic M, Gunther A. Mosaic hydrogels: one-step formation of multi-scale soft materials. Adv Mater. 2012;24(27): 3650-8.