Adipose tissue, recognized as an endocrine organ, plays a crucial role in regulating the repair processes of various damaged tissues, including the skin. This unique function suggests that adipose tissue could be engineered to regenerate other damaged organs. Three-dimensional (3D) bioprinting technology has significantly impacted regenerative medicine by enabling the creation of engineered and functional 3D organs and tissues, including adipose tissues. However, existing biofabrication techniques have struggled to replicate the native structure and densely packed lipid droplets of adipose tissue, limiting the therapeutic potential of 3D-printed adipose tissue.

To address this challenge, a team of researchers led by Assistant Professor Byoung Soo Kim from Pusan National University in Korea has developed an innovative biofabrication method for adipose tissue. Their findings, published online on February 2, 2025, in Advanced Functional Materials, describe a new hybrid bioink that overcomes some of the key limitations of current tissue biofabrication methods. The bioink combines 1% adipose-derived decellularized extracellular matrix (dECM) with 0.5% alginate. This hybrid bioink significantly restricts the migration of preadipocytes, the precursors to fat cells, while simultaneously promoting their differentiation into mature adipocytes.

Dr. Kim explains, “Under conventional culture conditions, preadipocytes tend to proliferate and migrate, which hinders the formation of lipid droplets essential for adipose tissue function. The hybrid bioink we developed helps maintain the physiological properties of adipose tissue while limiting these unwanted behaviors.”

Another key element of the study is the optimization of tissue structure for improved nutrient and oxygen delivery. The research suggests that a tissue diameter of ≤ 600 µm ensures sufficient nourishment for the bioprinted adipose tissue. Additionally, when the adipose tissues were arranged with a spacing of ≤ 1000 µm, they promoted adipogenesis through paracrine signaling, an important process for tissue growth and regeneration.

The optimized 3D-printed adipose tissues demonstrated promising in vitro results, particularly in their ability to enhance skin cell migration by modulating the expression of key cell migration-related proteins such as MMP2, COL1A1, KRT5, and ITGB1. To investigate the potential of this technology in vivo, the researchers created a tissue assembly consisting of both adipose and dermal modules and implanted it into mice with skin wounds. The results were striking—this tissue assembly accelerated wound healing by inducing re-epithelialization, remodeling of the tissue, blood vessel formation, and regulation of proteins related to skin cell differentiation.

These findings underscore the potential of 3D bioprinting as a pivotal technology in the field of precision medicine and regenerative healthcare. As the commercialization of 3D bioprinting technology progresses, it is expected to significantly impact the market for customized tissue manufacturing, with hospitals and research institutions increasingly adopting personalized bioprinting systems for patient treatment and medical research.

According to lead author Jae-Seong Lee, “The 3D bioprinted endocrine tissues show considerable promise in enhancing skin regeneration, making them valuable for regenerative medicine. Unlike current fat grafting methods, which suffer from low survival rates and gradual resorption, our hybrid bioinks enhance endocrine function and cell viability. This approach could help address chronic wound issues such as diabetic foot ulcers, pressure sores, and burns.”

This groundbreaking research paves the way for more effective and sustainable treatments in regenerative medicine, offering hope for improved healing and tissue regeneration in the future.

By Impact Lab