3D printed PLCL/hydrogel complex scaffolds using decellularized adipose tissue development
Adipose tissue regeneration has been studied for many patients who had a burn defect, traumatic injury and mastectomy to improve their quality of life. The number of surgical operations is increasing due to the increase in the number of patients newly diagnosed with breast cancer. Although the studies on adipose tissue regeneration using natural polymer and synthetic polymer have been done, but disadvantages such as fast degradation rate and mismatch of mechanical properties still exist. So we set up three strategies to overcome the limits of previous researches. First, poly (lactide-co-caprolactone) (PLCL), very elastic and biocompatible polymer, was synthesized to provide proper mechanical properties and three dimensional structure for adipose tissue engineering. It also provide a stable tertiary structure to prevent the fast degradation while the adipose tissue regenerate. Secondly, to induce adipogenic differentiation and neo-vascularization for large sized tissue, decellularized extracellular matrix (dECM) was used to promote angiogenesis for efficient blood supply. Lastly, 3D printing technique was used to fabricate a patient-specific scaffold.<br /> The PLCL and adipose tissue derived dECM hydrogel was printed through dual nozzle system and the complex construct composed of PLCL and hydrogel was fabricated (15 mm x 15 mm x 4.0 mm). Flexibility and stretchability of the PLCL copolymer were maintained after 3D printing. Adipose tissue derived dECM based hydrogel was prepared as a biocompatible bioink. Since 1:3-adECM: collagen showed the best cell viability and printability than other ratio of hydrogels, it was used for further experiments. We evaluated angiogenesis and macrophage infiltration of the samples while in vivo experiments and investigated the potential for adipose tissue regeneration. A lot of matured blood vessels were observed more in the Hydrogel-PLCL complex constructs than in PLCL only scaffolds. Moreover, the higher expression of M2 macrophage for tissue repair and of adipogenic differentiation relative genes was measured in the Hydrogel-PLCL complex constructs by immunofluorescent analysis and real-time PCR, respectively. Based on these results, we anticipate that our constructs will be a promising alternative for adipose tissue regeneration.