Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration

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dc.catalogadorjca
dc.contributor.authorChávez, Myra N.
dc.contributor.authorFuchs, Benedikt
dc.contributor.authorMoellhoff, Nicholas
dc.contributor.authorHofmann, Daniel
dc.contributor.authorZhang, Lifang
dc.contributor.authorSelão, Tiago Toscano
dc.contributor.authorGiunta, Riccardo E.
dc.contributor.authorEgaña, José Tomás
dc.contributor.authorNickelsen, Jörg
dc.contributor.authorSchenck, Thilo L.
dc.date.accessioned2024-02-27T16:02:45Z
dc.date.available2024-02-27T16:02:45Z
dc.date.issued2021
dc.description.abstractImpaired wound healing represents an unsolved medical need with a high impact on patients´ quality of life and global health care. Even though its causes are diverse, ischemic-hypoxic conditions and exacerbated inflammation are shared pathological features responsible for obstructing tissue restoration. In line with this, it has been suggested that promoting a normoxic pro-regenerative environment and accelerating inflammation resolution, by reinstating the lymphatic fluid transport, could allow the wound healing process to be resumed. Our group was first to demonstrate the functional use of scaffolds seeded with photosynthetic microorganisms to supply tissues with oxygen. Moreover, we previously proposed a photosynthetic gene therapy strategy to create scaffolds that deliver other therapeutic molecules, such as recombinant human growth factors into the wound area. In the present work, we introduce the use of transgenic Synechococcus sp. PCC 7002 cyanobacteria (SynHA), which can produce oxygen and lymphangiogenic hyaluronic acid, in photosynthetic biomaterials. We show that the co-culture of lymphatic endothelial cells with SynHA promotes their survival and proliferation under hypoxic conditions. Also, hyaluronic acid secreted by the cyanobacteria enhanced their lymphangiogenic potential as shown by changes to their gene expression profile, the presence of lymphangiogenic protein markers and their capacity to build lymph vessel tubes. Finally, by seeding SynHA into collagen-based dermal regeneration materials, we developed a viable photosynthetic scaffold that promotes lymphangiogenesis in vitro under hypoxic conditions. The results obtained in this study lay the groundwork for future tissue engineering applications using transgenic cyanobacteria that could become a therapeutic alternative for chronic wound treatment. STATEMENT OF SIGNIFICANCE: In this study, we introduce the use of transgenic Synechococcus sp. PCC 7002 (SynHA) cyanobacteria, which were genetically engineered to produce hyaluronic acid, to create lymphangiogenic photosynthetic scaffolds for dermal regeneration. Our results confirmed that SynHA cyanobacteria maintain their photosynthetic capacity under standard human cell culture conditions and efficiently proliferate when seeded inside fibrin-collagen scaffolds. Moreover, we show that SynHA supported the viability of co-cultured lymphatic endothelial cells (LECs) under hypoxic conditions by providing them with photosynthetic-derived oxygen, while cyanobacteria-derived hyaluronic acid stimulated the lymphangiogenic capacity of LECs. Since tissue hypoxia and impaired lymphatic drainage are two key factors that directly affect wound healing, our results suggest that lymphangiogenic photosynthetic biomaterials could become a treatment option for chronic wound management.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.actbio.2021.03.033
dc.identifier.issn1742-7061
dc.identifier.urihttps://doi.org/10.1016/j.actbio.2021.03.033
dc.identifier.urihttp://europepmc.org/abstract/med/33753313
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/81328
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Egaña Erazo, Jose Tomas; 0000-0003-2624-6992; 1018715
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final143
dc.pagina.inicio132
dc.revistaActa Biomaterialia
dc.rightsacceso restringido
dc.subjectOxygen
dc.subjectHypoxia
dc.subjectHyaluronic acid
dc.subjectSynechococcus sp. PCC 7002
dc.subjectLymphatic endothelial cells
dc.subjectBiomaterials
dc.subjectLymph vessels
dc.subject.ddc510
dc.subject.deweyMatemática física y químicaes_ES
dc.titleUse of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration
dc.typeartículo
dc.volumen126
sipa.codpersvinculados1018715
sipa.trazabilidadORCID;2024-01-15
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