Novel adipose tissue biofabrication approach paves the way for enhanced skin regeneration

The adipose tissue, which serves as an endocrine organ, releases various molecules that regulate the repair of other damaged tissues, including the skin. Hence, adipose tissues can potentially be reengineered to regenerate the damaged organs. Three-dimensional (3D) bioprinting technology has revolutionized regenerative medicine by enabling the generation of engineered and functional 3D organs or tissues, including adipose tissues. However, the currently used tissue biofabrication methods cannot replicate the native structure and densely packed lipid droplets of adipose tissues, hindering the therapeutic application of 3D-printed adipose tissues.

To overcome this limitation, a research team led by Assistant Professor Byoung Soo Kim from the Pusan National University, Korea, has developed a novel adipose tissue biofabrication approach. This paper was made available online on February 02, 2025 in Advanced Functional Materials. The highlight of this study was the development of a hybrid bioink, which is a combination of 1% adipose-derived decellularized extracellular matrix and 0.5% alginate. This hybrid bioink limited the migration of preadipocytes , the fat cell precursors, while promoting their differentiation. Dr. Kim states that "Under standard culture conditions, preadipocytes tend to proliferate and migrate, preventing the formation of lipid droplets that are essential for adipose tissue functions. The hybrid bioink developed in this study maintains the physiological properties of the adipose tissue." Additionally, a diameter of ≤ 600 µm was deemed to ensure sufficient nutrient and oxygen delivery for the fabricated adipose tissue. Furthermore, bioprinted adipose tissues arranged with a spacing of ≤ 1000 µm promoted adipogenesis via paracrine signaling. The optimized 3D bioprinted adipose tissues rapidly promoted the migration of skin cells in vitro by modulating the expression levels of cell migration-related proteins (MMP2, COL1A1, KRT5, and ITGB1).

To examine the in vivo effects of bioprinted adipose tissues, the authors prepared a tissue assembly comprising adipose and dermis modules. This tissue assembly was implanted into mice with skin wounds. The findings revealed that the tissue assembly promoted wound healing in mice by inducing re-epithelialization, tissue remodeling, and blood vessel formation and regulated the expression of skin cell differentiation-related proteins.

These results demonstrate bioprinting's potential as a core technology in precision medicine and regenerative healthcare, driving a new wave of medical innovation. With the commercialization of 3D bioprinting technology expected to fuel significant market growth in customized tissue manufacturing, hospitals and research institutes are likely to increasingly adopt personalized bioprinting systems for patient treatments and medical studies.

The method developed in this study has various implications. According to the lead author Jae-Seong Lee, "The 3D bioprinted endocrine tissues enhanced skin regeneration, indicating their potential applications in regenerative medicine. 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."