Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration

Abstract

The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy.

Oxygen delivering biomaterials for tissue engineering

“…In a subsequent study, algae were genetically engineered to secrete vascular endothelial growth factor (VEGF) to promote vascularization as well as provide O 2 in tissue constructs. 75 When the algae-incorporating collagen gels were implanted subcutaneously into mice, scaffolds with genetically modified algae had longer vessel formation, more CD31 positive cells, and higher levels of VEGF after 7 days post implantation. To further evaluate the regenerative potential of these photosynthetic biomaterials, more work is needed to determine whether the algae induced an inflammatory or immune response in vivo .…”

REDV–polyethyleneimine complexes for selectively enhancing gene delivery in endothelial cells

“…25 Gene therapy, which has been widely applied in anti-tumor agents and bone tissue engineering, could also provide an alternative and promising option to promote endothelialization from the transfected ECs. 1,[26][27][28][29][30][31][32][33][34][35] Besides the commonly used vascular endothelial growth factor (VEGF) gene, the ZNF580 gene is also a good choice due to the fact that the overexpression of the ZNF580 gene in EA.hy926 cells leads to the enhanced expression of the VEGF protein, and the migration and proliferation of the cells. 36 As the half-time of therapeutic DNAs could be limited to a few minutes resulting from potential degradation by endonucleases in physiological fluids and the extracellular space, 20 gene carriers play an important role for successful gene transfection, especially for ECs which are one of the most difficult cell types to be transfected.…”

The Potential of Algal Biotechnology to Produce Antiviral Compounds and Biopharmaceuticals

“…Thus far the following cytokines have been targeted: High mobility group protein B1 (HMGB1), Tumor necrosis factor α (TNF-α), Tumor necrosis factor-related apoptosis inducing ligand (TRAIL), Human vascular endothelial growth factor (VEGF), Human interferon β1 (IFN-β1), and IFN-α2a. The former was produced in D. salina , while the rest were produced in C. reinhardtii [ 184 , 185 , 186 ]. Nevertheless, this group of biopharmaceuticals has been characterized at very preliminary stages with the exception of IFN-α2a, which showed inhibitory effects on the propagation of the Vesicular stomatitis virus and malignant cells in vivo [ 187 ].…”