Novel strategy for multi-material 3D bioprinting of human stem cell based corneal stroma with heterogenous design.

Three-dimensional (3D) bioprinting offers an automated, customizable solution to manufacture highly detailed 3D tissue constructs and holds great promise for regenerative medicine to solve the severe global shortage of donor tissues and organs. However, uni-material 3D bioprinting is not sufficient for manufacturing heterogenous 3D constructs with native-like microstructures and thus, innovative multi-material solutions are required. Here, we developed a novel multi-material 3D bioprinting strategy for bioprinting human corneal stroma. The human cornea is the transparent outer layer of your eye, and vision loss due to corneal blindness has serious effects on the quality of life of individuals. One of the main reasons for corneal blindness is the damage in the detailed organization of the corneal stroma where collagen fibrils are arranged in layers perpendicular to each other and the corneal stromal cells grow along the fibrils. Donor corneas for treating corneal blindness are scarce, and the current tissue engineering (TE) technologies cannot produce artificial corneas with the complex microstructure of native corneal stroma. To address this, we developed a novel multi-material 3D bioprinting strategy to mimic detailed organization of corneal stroma. These multi-material 3D structures with heterogenous design were bioprinted by using human adipose tissue -derived stem cells (hASCs) and hyaluronic acid (HA) -based bioinks with varying stiffnesses. In our novel design of 3D models, acellular stiffer HA-bioink and cell-laden softer HA-bioink were printed in alternating filaments, and the filaments were printed perpendicularly in alternating layers. The multi-material bioprinting strategy was applied for the first time in corneal stroma 3D bioprinting to mimic the native microstructure. As a result, the soft bioink promoted cellular growth and tissue formation of hASCs in the multi-material 3D bioprinted composites, whereas the stiff bioink provided mechanical support as well as guidance of cellular organization upon culture. Interestingly, cellular growth and tissue formation altered the mechanical properties of the bioprinted composite constructs significantly. Importantly, the bioprinted composite structures showed good integration to the host tissue in

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© 2023 The Authors.

Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Heli Skottman reports financial support was provided by Jane and Aatos Erkko Foundation. Anni Mörö reports financial support was provided by 10.13039/501100002341Academy of Finland. Susanna Miettinen reports financial support was provided by 10.13039/501100002341Academy of Finland. Paula Puistola reports financial support was provided by 10.13039/501100003125Finnish Cultural Foundation. Paula Puistola reports financial support was provided by 10.13039/501100013510Eye and Tissue Bank Foundation. Anni Mörö reports a relationship with StemSight Oy that includes: equity or stocks. Heli Skottman reports a relationship with StemSight Oy that includes: equity or stocks. Anni Mörö has patent #PCT/FI2022/050,403 pending to Assignee. Based on the Act on the Right in Inventions in Finland, all authors employed by Tampere University have given all rights to the University and thus have declared no competing interests. Anni Mörö and Heli Skottman are co-founders and shareholders in StemSight Ltd without any connection to the technology and results reported in this manuscript. The other authors declare no conflicts of interests.