A First in Human Trial Implanting Microalgae Shows Safety of Photosynthetic Therapy for the Effective Treatment of Full Thickness Skin Wounds

Abstract

Insufficient oxygen supply represents a relevant issue in several fields of human physiology and medicine. It has been suggested that the implantation of photosynthetic cells can provide oxygen to tissues in the absence of a vascular supply. This approach has been demonstrated to be successful in several in vitro and in vivo models; however, no data is available about their safety in human patients. Here, an early phase-1 clinical trial (ClinicalTrials.gov identifier: NCT03960164, https://clinicaltrials.gov/ct2/show/NCT03960164) is presented to evaluate the safety and feasibility of implanting photosynthetic scaffolds for dermal regeneration in eight patients with full-thickness skin wounds. Overall, this trial shows that the presence of the photosynthetic microalgae Chlamydomonas reinhardtii in the implanted scaffolds did not trigger any deleterious local or systemic immune responses in a 90 days follow-up, allowing full tissue regeneration in humans. The results presented here represent the first attempt to treat patients with photosynthetic cells, supporting the translation of photosynthetic therapies into clinics.Clinical Trial Registration:www.clinicaltrials.gov/ct2/show/NCT03960164, identifier: NCT03960164.

Selection of a suitable photosynthetically active microalgae strain for the co-cultivation with mammalian cells

“…Although the culture conditions, 30°C and a simple mix medium of mammalian cell culture and algal medium (50:50 mixture), were a compromise for both species, the expression of the hypoxia-inducible factor HIF-1α in the fibroblasts could be reduced by the presence of microalgae. Follow-up studies of this team demonstrated the biocompatibility, safety and potential applicability of microalgae-laden commercial collagen scaffolds for photosynthetic therapies in a mouse full skin defect as well as in a first clinical trial comprising eight patients with full thickness skin wounds ( Schenck et al, 2015 ; Chávez et al, 2016 ; Obaíd et al, 2021 ).…”

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

“…This approach has been described by our group in recent in vitro ( Hopfner et al, 2014 ; Centeno-Cerdas et al, 2018 ; Chávez et al, 2021 ) and in vivo ( Schenck et al, 2015 ; Chávez et al, 2016 ) studies, and further confirmed by other independent groups, highlighting its potential application in several medical fields, including tissue engineering and regeneration ( Yamaoka et al, 2012 ; Evron et al, 2015 ; Haraguchi et al, 2017 ; Chen et al, 2020 ), heart ischemia ( Cohen et al, 2017 ), and tumor treatment ( Huo et al, 2020 ; Liu et al, 2020 ; Qiao et al, 2020 ). Moreover, an ongoing clinical trial is confirming its safety for tissue regeneration in humans ( Obaíd et al (2021) accepted for publication. ClinicalTrials.gov Identifier: NCT03960164).…”

Oxygenation therapies for improved wound healing: current trends and technologies

“…Together these results suggest the clinical translation potential of photosynthetic biomaterials. 105…”