Adipose tissue, acting as an endocrine organ, releases various molecules that play a significant role in the repair of other damaged tissues, including the skin. This suggests that adipose tissue could be reengineered to help regenerate damaged organs. Three-dimensional (3D) bioprinting technology has revolutionized regenerative medicine by allowing the creation of functional and engineered 3D tissues and organs, including adipose tissues. However, existing tissue biofabrication techniques are unable to replicate the dense structure and lipid droplets characteristic of native adipose tissues, which limits the therapeutic application of 3D-printed adipose tissues. To address this challenge, researchers have developed a new adipose tissue biofabrication approach, as detailed in a study published in Advanced Functional Materials.

The key innovation in this study, led by researchers at Pusan National University (Busan, Korea), was the creation of a hybrid bioink that combines 1% adipose-derived decellularized extracellular matrix and 0.5% alginate. This hybrid bioink was designed to restrict the migration of preadipocytes, which are precursor cells to fat cells, while simultaneously promoting their differentiation. In conventional culture conditions, preadipocytes tend to proliferate and migrate, which hinders the formation of lipid droplets—critical for adipose tissue functions. The hybrid bioink developed in this study preserves the physiological properties of adipose tissue. Additionally, the researchers determined that a diameter of ≤ 600 µm was optimal for ensuring the delivery of sufficient nutrients and oxygen to the fabricated adipose tissue. Moreover, bioprinted adipose tissues with a spacing of ≤ 1000 µm enhanced adipogenesis through paracrine signaling. These optimized 3D bioprinted adipose tissues also accelerated the migration of skin cells in vitro by modulating the expression of proteins involved in cell migration, including MMP2, COL1A1, KRT5, and ITGB1.

To assess the in vivo effects of the bioprinted adipose tissues, the researchers prepared a tissue assembly that combined adipose and dermis modules. This assembly was then implanted into mice with skin wounds. The results showed that the tissue assembly significantly promoted wound healing by enhancing re-epithelialization, tissue remodeling, and blood vessel formation. Furthermore, the assembly regulated the expression of proteins involved in skin cell differentiation. These findings highlight the potential of bioprinting as a pivotal technology in precision medicine and regenerative healthcare, driving advancements in medical innovation. With the expected commercialization of 3D bioprinting technology leading to considerable market growth in customized tissue manufacturing, hospitals and research institutions are likely to increasingly adopt personalized bioprinting systems for patient treatments and medical studies. According to the researchers, the method developed in this study holds multiple implications for the future of tissue engineering and regenerative medicine.

“The 3D bioprinted endocrine tissues enhanced skin regeneration, indicating their potential applications in regenerative medicine,” said lead author Jae-Seong Lee. “While current fat grafting procedures suffer from low survival rates and gradual resorption, our hybrid bioinks enhance endocrine function and cell viability, potentially overcoming these limitations. This approach could be particularly valuable for treating chronic wounds such as diabetic foot ulcers, pressure sores, and burns.” 

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