However, their inherent disadvantages such as high cost, difficulty to be accurately released and short half-life in vivo limit their applications in clinical practice. basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF-1) ) have been applied to incorporate with 3D-printed scaffold to induce better adipogenesis and angiogenesis. Accordingly, several endogenous angiogenic factors (e.g. It is well established that the efficiency of adipogenic differentiation and sufficient vascularization are crucial for successful adipose tissue reconstruction. Nevertheless, the activity of adipose tissue regeneration mediated by this single-component GelMA scaffold is not significant enough for clinical application. proved that both human primary mature adipocytes and adipose-derived stem cells could survive well in the 3D-printed GelMA hydrogels with the phenotype of adipocytes. Among several hydrogels used for 3D-printed scaffolds (alginate, hyaluronic acid, collagen, silk fibroin, chitosan, etc.), gelatin methacrylate anhydride (GelMA) is a promising candidate in adipose tissue engineering due to its ease of crosslinking by ultraviolet (UV) irradiation, low antigenicity and good biocompatibility. polycaprolactone), the 3D printing of hydrogels represents an advantageous alternative because of their extracellular matrix-mimicking structural network and good biomimetics of adipose tissue mechanical properties. Compared to conventional scaffolds made of thermoplastic materials (e.g. Three-dimensional (3D)-printed scaffold-guided adipose tissue engineering is attracting more and more attention as a promising technique to repair injured breasts, especially for large-volume defects, in which the scaffold is utilized as a ‘bridge’ to facilitate cellular interactions and tissue formation. Therefore, the development of an innovative treatment strategy with high activity for adipose tissue regeneration and precise structure control ability for implanted construct is urgently needed. Besides, since breast reconstruction is particularly personalized, additional breast plastic surgery is usually required after the treatments of these strategies due to the lack of precise shape control. All these disadvantages increase the risk of delayed adipose tissue regeneration and failure of breast repair. Although current strategies, including lipofilling, autologous-tissue flap transplantation and silicone prostheses implantation, have been widely practiced for breast reconstruction, they have numerous drawbacks and limitations, such as uncontrollable resorption of fats, source limitation of autologous-tissue flap and capsule contracture of silicone prosthesis. The restoration of adipose tissue is required in many clinical scenarios, such as mastectomies following breast cancer, which usually result in the absence of breast tissue and cause severe psychological and physiological burdens to patients. These findings suggest that 3D-printed GelMA/CS composite scaffolds might be a good candidate for adipose tissue engineering. Moreover, the composite scaffold promoted vascularized adipose tissue restoration under the skin of nude mice in vivo. The in vitro experiments showed that the composite hydrogel scaffolds could not only be customized with controllable architectures, but also significantly stimulated both 3T3-L1 preadipocytes and human umbilical vein endothelial cells in multiple cell behaviors, including cell adhesion, proliferation, migration and differentiation. Here, a composite hydrogel scaffold was prepared by three-dimensional (3D) printing technology, applying gelatin methacrylate anhydride (GelMA) as printing ink and calcium silicate (CS) bioceramic as an active ingredient for breast adipose tissue regeneration. However, the therapeutic effect of current clinical strategies is not satisfying due to the high demand of personalized customization and the timely vascularization in the process of adipose regeneration. The increased number of mastectomies, combined with rising patient expectations for cosmetic and psychosocial outcomes, has necessitated the use of adipose tissue restoration techniques.
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