Dual Extrusion Patterning Drives Tissue Development Aesthetics and Shape Retention in 3D Printed Nipple-Areola Constructs.

Breast cancer and its most radical treatment, the mastectomy, significantly impose both physical transformations and emotional pain in thousands of women across the globe. Restoring the natural appearance of a nipple-areola complex directly on the reconstructed breast represents an important psychological healing experience for these women and remains an unresolved clinical challenge, as current restorative techniques render a flattened disfigured skin tab within a single year. To provide a long-term solution for nipple reconstruction, this work presents 3D printed hybrid scaffolds composed of complementary biodegradable gelatin methacrylate and synthetic non-degradable poly(ethylene) glycol hydrogels to foster the regeneration of a viable nipple-areola complex. In vitro results showcased the robust structural capacity and long-term shape retention of the nipple projection amidst internal fibroblastic contraction, while in vivo subcutaneous implantation of the 3D printed nipple-areola demonstrated minimal fibrotic encapsulation, neovascularization, and the formation of healthy granulation tissue. Envisioned as subdermal implants, these nipple-areola bioprinted regenerative grafts have the potential to transform the appearance of the newly reconstructed breast, reduce subsequent surgical intervention, and revolutionize breast reconstruction practices.

Liposomal SDF-1 Alpha Delivery in Nanocomposite Hydrogels Promotes Macrophage Phenotype Changes and Skin Tissue Regeneration.

Skin regeneration in chronic wounds is often delayed due to persistent inflammation induced by underlying conditions such as diabetes. This effect is mediated, in part, by macrophages present in the wound, which can be stimulated to adopt either pro- or anti-inflammatory phenotypes depending on the status of the local microenvironment. In this work, the prohealing chemokine stromal cell-derived factor-1 alpha (SDF-1α) is controllably released from a hydrogel-based biomaterial to promote skin tissue regeneration and wound closure. This innovative nanocomposite hydrogel system releases liposomal stromal cell-derived factor-1 alpha (lipoSDF) as a new treatment approach for dorsal full-thickness skin wounds in wild-type and diabetic mice. Using this strategy, the recruitment and polarization of macrophages primarily of the anti-inflammatory phenotype were observed, along with a decreased amount of open wound surface area in diabetic mice after 28 days. This was accompanied by histological observations of increased epidermal stratification and dermal angiogenesis. These findings represent an important step of investigation distinctive in its field for developing immunomodulatory biomaterials that are able to influence macrophage phenotype and promote healing as hydrogel-based wound dressings.

Fabrication of centimeter-sized 3D constructs with patterned endothelial cells through assembly of cell-laden microbeads as a potential bone graft.

Modular tissue engineering is a promising biofabrication strategy to create engineered bone grafts in a bottom-up manner, in which cell-laden micro-modules are prepared as basic building blocks to assemble macroscopic tissues via different integrating mechanisms. In this study, we prepared collagen microbeads loaded with human bone marrow derived mesenchymal stem cells (BMSCs) using a microfluidic approach. The cell-laden microbeads were characterized for size change, cell activity, osteogenesis, as well as their self-assembly properties to generate centimeter-sized constructs. Moreover, using the cell-laden beads as a supporting medium, induced pluripotent stem cell-derived endothelial cells (iPSC-EC) were patterned inside bead aggregates through extrusion-based 3D printing. This fabrication approach that combines modular tissue engineering and supports 3D printing has the potential to create 3D engineered bone grafts with a pre-existing, customized vasculature.