Speaker
Description
Introduction
One of the most significant challenges in organ bioengineering is developing functional vascular networks. Proper vascularization is critical for transporting oxygen, nutrients, and signaling molecules, while also removing waste. In bionic organs, poor vessel formation limits nutrient exchange and cell migration, reducing transplant quality and long-term survival [1], [2]. The traditional use of mature endothelial cells is restricted by their low proliferation and limited angiogenic capacity. Endothelial progenitor cells - particularly endothelial colony-forming cells (ECFCs) - exhibit greater angiogenic potential. This study explores vascularization strategies in a 3D bioprinted pancreas model to advance the functionality of bioengineered organs.
Materials and Methods
A prototype of a bionic pancreas was created using 3D bioprinting, incorporating bioink composed of decellularized extracellular matrix (dECM), pancreatic cells, endothelial cells, and fibroblasts. The selection of biomaterials for the 3D bioprinting of a bionic pancreas integrated with a flow system was guided by comprehensive hemocompatibility assessment tests to ensure optimal interaction with blood components and minimize the risk of thrombogenic or immunological responses. A central pre-designed vascular channel was included to mimic native vasculature. The printed construct was placed in a perfusion bioreactor, simulating physiological flow. After several days of incubation, samples were fixed and analyzed by immunohistochemistry (IHC) using markers such as CD31, insulin, vimentin, and glucagon to evaluate vascular and islet formation. To determine the optimal conditions for vessel formation, microfluidic models with different concentrations of endothelial cells to fibroblasts were designed. Furthermore, isolation and co-culture techniques were improved to enhance the angiogenic potential of the endothelial population. Models are characterized by IHC and qPCR for the following markers: VEGF, Tie2 and Ang1.
Discussion
These early observations highlight the persistent difficulty of achieving sufficient vascularization in bioprinted organs. While the emergence of vessel-like structures is encouraging, further work is needed to improve vascular density and functionality. Adjusting the endothelial-to-fibroblast ratio and improving cell culture protocols could enhance vessel formation. Generating more angiocompetent endothelial populations is expected to support the development of stable and functional microvasculature. Continued optimization will be vital for improving transplant performance and advancing bioengineered organ systems toward clinical application. This study provides initial evidence of successful vascular integration and sets the stage for future investigations focused on enhancing vascular complexity and tissue viability.
Results
Preliminary analysis show microvessel-like structures forming from the central vascular channel in the bioprinted pancreas. These structures tested positive for CD31, indicating early capillary development. Although the number of vessels is limited, their alignment along the direction of perfusion suggests that mechanical flow may promote endothelial organization and sprouting. Microscopic images (to be shown) confirm the physical continuity between the main channel and newly formed vascular outgrowths.
References
[1] Zheng, K., Chai, M., Luo, B., Cheng, K., Wang, Z., Li, N., & Shi, X. (2024). Recent progress of 3D printed vascularized tissues and organs. Smart Materials in Medicine, 5(2), 183–195.
[2] Khan, O. F., & Sefton, M. V. (2011). Endothelialized biomaterials for tissue engineering applications in vivo. Trends in Biotechnology, 29(8), 379–387.
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