Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants

• Published in: Advanced materials (Weinheim) 2019-01, Vol.31 (1), p.e1803895-n/a
• Main Authors: Edri, Reuven, Gal, Idan, Noor, Nadav, Harel, Tom, Fleischer, Sharon, Adadi, Nofar, Green, Ori, Shabat, Doron, Heller, Lior, Shapira, Assaf, Gat‐Viks, Irit, Peer, Dan, Dvir, Tal
• Format: Article
• Language: English
• Subjects: Animals; autologous; Bioengineering; Cell Differentiation; Cellular Reprogramming; decellularized hydrogels; Differentiation (biology); Endothelial Cells - cytology; Endothelial Cells - immunology; Endothelial Cells - transplantation; Extracellular Matrix - immunology; Extracellular Matrix - metabolism; Humans; Hydrogels; Hydrogels - chemistry; Immune system; Implants; induced pluripotent stem cells; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - cytology; Myocytes, Cardiac - immunology; Myocytes, Cardiac - transplantation; non‐immunogenic; Omentum - cytology; Omentum - immunology; Omentum - metabolism; Prostheses and Implants; Rejection; Scaffolding; Spinal cord; Stem cells; Swine; Tissue Engineering; Tissue Scaffolds; Transplantation, Autologous; Transplants & implants
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.201803895

Despite incremental improvements in the field of tissue engineering, no technology is currently available for producing completely autologous implants where both the cells and the scaffolding material are generated from the patient, and thus do not provoke an immune response that may lead to implant rejection. Here, a new approach is introduced to efficiently engineer any tissue type, which its differentiation cues are known, from one small tissue biopsy. Pieces of omental tissues are extracted from patients and, while the cells are reprogrammed to become induced pluripotent stem cells, the extracellular matrix is processed into an immunologically matching, thermoresponsive hydrogel. Efficient cell differentiation within a large 3D hydrogel is reported, and, as a proof of concept, the generation of functional cardiac, cortical, spinal cord, and adipogenic tissue implants is demonstrated. This versatile bioengineering approach may assist to regenerate any tissue and organ with a minimal risk for immune rejection. Fatty tissues are extracted from patients and the cellular and a‐cellular materials are separated. While the cells are reprogrammed to induced pluripotent stem cells (iPSCs), the extracellular matrix is processed to a personalized, nonimmunogenic hydrogel. The iPSCs are encapsulated within the hydrogel and differentiated to engineer autologous cardiac, cortical, dopaminergic, spinal cord, and adipogenic implants.