In Situ 3D Bioprinting Living Photosynthetic Scaffolds for Autotrophic Wound Healing

Abstract

Three-dimensional (3D) bioprinting has been extensively explored for tissue repair and regeneration, while the insufficient nutrient and oxygen availability in the printed constructs, as well as the lack of adaptive dimensions and shapes, compromises the overall therapeutic efficacy and limits their further application. Herein, inspired by the natural symbiotic relationship between salamanders and algae, we present novel living photosynthetic scaffolds by using an in situ microfluidic-assisted 3D bioprinting strategy for adapting irregular-shaped wounds and promoting their healing. As the oxygenic photosynthesis unicellular microalga (Chlorella pyrenoidosa) was incorporated during 3D printing, the generated scaffolds could produce sustainable oxygen under light illumination, which facilitated the cell proliferation, migration, and differentiation even in hypoxic conditions. Thus, when the living microalgae-laden scaffolds were directly printed into diabetic wounds, they could significantly accelerate the chronic wound closure by alleviating local hypoxia, increasing angiogenesis, and promoting extracellular matrix (ECM) synthesis. These results indicate that the in situ bioprinting of living photosynthetic microalgae offers an effective autotrophic biosystem for promoting wound healing, suggesting a promising therapeutic strategy for diverse tissue engineering applications.

Structural and biological engineering of 3D hydrogels for wound healing

“…Microfluidic techniques can control single or multiple fluids in microscale channels ranging from tens to hundreds of microns [ 90 ]. The combination of microfluidic technologies and traditional 3D printing platforms allows for fine control of the compositional and structural features of tissue engineering scaffolds throughout the printing process [ 90 ].…”

“…Because an oxygenic photosynthetic unicellular microalga ( Chlorella pyrenoidosa ) was introduced during 3D printing, the resulting constructs could continuously supply oxygen under light irradiation, promoting cell proliferation, migration, and differentiation, even under hypoxia. By reducing local hypoxia, enhancing angiogenesis, and encouraging extracellular matrix (ECM) formation, the microalgae-laden scaffolds printed directly into diabetic wounds greatly sped up chronic wound closure [ 90 ].…”

The development of live microorganism-based oxygen shuttles for enhanced hypoxic tumor therapy

“…Zhao et al. designed a Chlorella -based live scaffold that adapted to irregularly shaped wounds and promoted their healing using an in situ microfluidic-assisted 3D bioprinting strategy [ 94 ]. Because photosynthetic protein nucleoli were introduced during 3D printing, this scaffold produced sustainable oxygen under light and promoted cell proliferation, migration and differentiation even under low oxygen conditions.…”

Development of in situ bioprinting: A mini review

“…However, these oxygen-generating compounds cannot sustain sufficient oxygen release over the entire healing process (Shiekh et al, 2020;Guan et al, 2021). To address this issue, Wang et al incorporated living photosynthetic microalgae into their bioink to deliver a continuous supply of oxygen to the target tissue after in situ bioprinting (Wang et al, 2022). The microalgae-laden bioink enhanced chronic wound healing in mice after illuminating the bioprinted scaffold with LED light.…”