We present a handheld skin printer that enables the in situ formation of biomaterial and skin tissue sheets of different homogeneous and architected compositions. When manually positioned above a target surface, the compact instrument (weight <0.8 kg) conformally deposits a biomaterial or tissue sheet from a microfluidic cartridge. Consistent sheet formation is achieved by coordinating the flow rates at which bioink and cross-linker solution are delivered, with the speed at which a pair of rollers actively translate the cartridge along the surface. We demonstrate compatibility with dermal and epidermal cells embedded in ionically cross-linkable biomaterials (e.g., alginate), and enzymatically cross-linkable proteins (e.g., fibrin), as well as their mixtures with collagen type I and hyaluronic acid. Upon rapid crosslinking, biomaterial and skin cell-laden sheets of consistent thickness, width and composition were obtained. Sheets deposited onto horizontal, agarose-coated surfaces were used for physical and in vitro characterization. Proof-of-principle demonstrations for the in situ formation of biomaterial sheets in murine and porcine excisional wound models illustrate the capacity of depositing onto inclined and compliant wound surfaces that are subject to respiratory motion. We expect the presented work will enable the in situ delivery of a wide range of different cells, biomaterials, and tissue adhesives, as well as the in situ fabrication of spatially organized biomaterials, tissues, and biohybrid structures.

The current standard of care for patients with severe large-area burns consists of autologous skin grafting or acellular dermal substitutes. While emerging options to accelerate wound healing involve treatment with allogeneic or autologous cells, delivering cells to clinically relevant wound topologies, orientations, and sizes remains a challenge. Here, we report the one-step in-situ formation of cell-containing biomaterial sheets using a handheld instrument that accommodates the topography of the wound. In an approach that maintained cell viability and proliferation, we demonstrated conformal delivery to surfaces that were inclined up to 45 degrees with respect to the horizontal. In porcine pre-clinical models of full-thickness burn, we delivered mesenchymal stem/stromal cell-containing fibrin sheets directly to the wound bed, improving reepithelialization, dermal cell repopulation, and neovascularization, indicating that this device could be introduced in a clinical setting improving dermal and epidermal regeneration.

surfaces and may not be applicable to fabrication of 3D wrinkled surfaces. The fi rst strategy may introduce local stress concentrations on 3D surface as the substrate is globally stretched and thus may form undesired wrinkles on the surface. The second one has the potential to create wrinkles on curved surfaces, but it generates wrinkles on the surfaces without 3D spatial control. [ 35,36 ] Methods that can facilely make 3D microstructured surfaces with tunable and controllable wrinkles are still not available, essentially limiting their applications to planar surface. Given the distinctive morphology of wrinkles and its proven functional roles in various 2D applications, creation of artifi cial 3D wrinkled surfaces, mimicking the diverse morphologies of wrinkles on nonplanar surfaces appearing in nature, may offer enhanced surface platforms and extend current 2D applications into a new dimension.Here, we demonstrate the formation of spatially tunable and controllable wrinkles on 2D/3D microstructured surfaces. In this microfabrication, fi rst we use photolithography to create polymeric 3D features with conformal partially-cured-polymer (PCP) layers by applying precisely controlled UV exposure. By projecting UV light via a photomask, we polymerize a prepolymer solution of poly(ethylene glycol) diacrylate (PEG-DA) in between a glass substrate and a PDMS slit channel ( Figure S1, Supporting Information) to create the 2D and 3D surfaces. The initial presence of oxygen in the prepolymer solution inhibits the polymerization until the oxygen is gradually depleted by the UV-initiated free radicals. [ 37 ] Because of the continuous diffusion of oxygen from the surrounding environment via the PDMS while no oxygen has penetrated from the glass, nonuniform polymerization across the channel height occurs and a PCP layer is created. The polymerization starts from the glass side and grows with a partially cured outer layer where the oxygen is being consumed by the UV-initiated free radicals (see the simulation of the polymerization progress in Figure S2, Supporting Information). When the UV is turned off, the polymerization stops and a photomask-defi ned 2D/3D microstructure is formed with a cured-body (foundation) and a PCP layer. This PCP layer is comprised of a semi-crosslinked PEG polymer network and uncured monomers trapped inside the network. The layer thickness is determined by the UV exposure time ( Figure S2, Supporting Information). After applying the photolithography, we gently rinse the sample to remove the uncured monomers, while retain those monomers trapped in the PCP layer. Finally, we treat the sample surface with plasma to create 2D/3D wrinkled microstructures (see Experimental Section). The charged ions of the plasma crosslink the PCP layer and slightly modify its mechanical properties, turning the PCP layer into a thin crust. Moreover, the continuous plasma also expands the thin crust, thus introduces in-plane compressive stresses in the Surface wrinkles are ubiquitous in nature and are used as a strategy ...