3D-printed bone scaffold with glowing blood vessels and hydrogels

3D-Printed Bone Scaffolds: The Future of Healing?

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Combining cutting-edge 3D printing with bioactive hydrogels and cell co-culture to revolutionize bone regeneration and prevascularization for better healing."

Vascularization, the development of blood vessels, is crucial for the success of large bone constructs in bone tissue engineering. It ensures that the newly formed bone tissue receives an adequate supply of oxygen and nutrients, facilitating its growth and integration with the host tissue. However, achieving sufficient vascularization in engineered bone grafts remains a significant challenge.

To address this challenge, researchers are exploring innovative strategies that combine 3D printing with hydrogel-based prevascularization techniques. This approach involves creating porous bone scaffolds using 3D printing, coating them with bioactive hydrogels containing human adipose-derived mesenchymal stem cells (ADMSC) and human umbilical vein endothelial cells (HUVEC), and then co-culturing these cells to promote vascularization.

This article delves into a study that utilizes this combined approach to generate pre-vascularized bone constructs. It examines how 3D printing, bioactive hydrogels, and cell co-culture work together to enhance bone regeneration and vascularization, offering new possibilities for treating large bone defects and improving patient outcomes.

How Does the Combination of 3D Printing, Hydrogels, and Cell Co-Culture Enhance Bone Regeneration?

3D-printed bone scaffold with glowing blood vessels and hydrogels

The study's methodology involved several key steps. First, researchers encapsulated ADMSC and HUVEC within bioactive hydrogels made from hyaluronic acid (HA) and gelatin. These hydrogels provided a supportive environment for the cells, allowing them to interact and form capillary-like networks.

Next, the cell-laden hydrogels were coated onto 3D-printed polycaprolactone/hydroxyapatite (PCL/HAp) scaffolds. These scaffolds provided structural support and mimicked the natural bone environment, encouraging cell attachment and growth. The constructs were then cultured in hybrid media to assess vascularization and osteogenesis.

Here are the key techniques that promote faster healing:

Cell Encapsulation: ADMSC and HUVEC are mixed and then loaded inside silicone molds and exposed to UV light.
Cellular Spheroid Encapsulation: ADMSC or ADMSC-HUVEC cell spheroids are created and then encapsulated within hydrogels and kept in hybrid media.
Composite Constructs: 3D printing of PCL/HAp scaffolds and incorporation of cell-laden hydrogels that are either ADMSC or ADMSC-HUVEC. ADMSC-HUVEC can also be surface seeded onto PCL/Hap scaffolds.

Finally, the prevascularized constructs were implanted into nude mice to evaluate their in vivo vascularization capacity and functionality. The results demonstrated that the 3D co-cultured ADMSC-HUVEC constructs generated capillary-like networks within the porous scaffolds, promoting in vitro vascularization without significantly affecting osteogenesis. Moreover, the hydrogel systems facilitated microvessel and lumen formation, encouraging anastomosis of human-origin vascular networks with the host's vasculature.

What Does This Mean for the Future of Bone Defect Treatments?

The findings of this study highlight the potential of prevascularized 3D printed scaffolds with anatomical shapes for healing larger bone defects. By combining 3D printing precision with the bioactive properties of hydrogels and cell co-culture, researchers can create constructs that not only provide structural support but also actively promote vascularization and integration with the host tissue.

This approach represents a significant step forward in bone tissue engineering, offering a promising solution to the challenges associated with large bone defect treatments. The ability to generate patient-specific scaffolds with enhanced vascularization could lead to improved patient outcomes, reduced complications, and faster healing times.

Further research and development in this area could pave the way for clinical translation, bringing the benefits of prevascularized 3D printed bone scaffolds to patients in need of bone reconstruction and regeneration.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1002/jbm.b.33994, Alternate LINK

Title: Prevascularization Of 3D Printed Bone Scaffolds By Bioactive Hydrogels And Cell Co-Culture

Subject: Biomedical Engineering

Journal: Journal of Biomedical Materials Research Part B: Applied Biomaterials

Publisher: Wiley

Authors: Mitchell A. Kuss, Shaohua Wu, Ying Wang, Jason B. Untrauer, Wenlong Li, Jung Yul Lim, Bin Duan

Published: 2017-09-13

Everything You Need To Know

How does the combination of 3D printing, hydrogels, and cell co-culture improve bone regeneration?

The combination of 3D printing, bioactive hydrogels, and cell co-culture significantly enhances bone regeneration by creating a supportive environment for cell growth and promoting vascularization. 3D printing allows for the creation of porous bone scaffolds, typically using PCL/HAp, providing structural support. These scaffolds are then coated with bioactive hydrogels, often made from hyaluronic acid (HA) and gelatin, which encapsulate ADMSC and HUVEC. The hydrogels offer a favorable environment for the cells to interact and form capillary-like networks. Finally, cell co-culture, the simultaneous culture of ADMSC and HUVEC, further enhances vascularization. This collaborative approach ensures the newly formed bone tissue receives adequate oxygen and nutrients, fostering its growth and integration with the host tissue, leading to better healing outcomes.

Why is vascularization so important in bone tissue engineering?

Vascularization is the development of blood vessels within the newly formed bone tissue. It is critical for the success of large bone constructs because it ensures the delivery of oxygen and nutrients necessary for bone tissue to grow and integrate with the host tissue. Without sufficient vascularization, the newly formed bone tissue may not survive, leading to graft failure. The article highlights the importance of vascularization and how techniques like cell co-culture of ADMSC and HUVEC, encapsulated within bioactive hydrogels, and integrated with 3D-printed PCL/HAp scaffolds, aim to address this challenge by promoting the formation of capillary-like networks within the bone grafts.

What is the role of 3D printing in this bone regeneration process?

3D printing is utilized to create porous bone scaffolds, most often using PCL/HAp, which mimic the natural bone structure. This provides a physical framework that supports cell attachment and growth, which encourages bone regeneration. The precision of 3D printing allows for the creation of scaffolds with specific shapes and sizes, which is crucial for treating large bone defects. The scaffolds are then coated with bioactive hydrogels. These hydrogels, which encapsulate ADMSC and HUVEC, act as a delivery system, releasing cells into the scaffold and promoting vascularization and osteogenesis. This integrated approach of 3D printing and hydrogels ensures that the construct not only provides structural support but also actively promotes the biological processes of bone healing.

What is the significance of bioactive hydrogels in this process?

Bioactive hydrogels, such as those made from hyaluronic acid (HA) and gelatin, play a critical role by providing a supportive environment for the encapsulated ADMSC and HUVEC. These hydrogels mimic the extracellular matrix, encouraging cell attachment, proliferation, and differentiation. They facilitate the interaction of the cells, promoting the formation of capillary-like networks, which is essential for vascularization. They also release cells into the scaffold environment. The use of bioactive hydrogels enhances the overall effectiveness of the bone regeneration process, by creating a favorable environment for the cells and promoting vascularization.

What are the potential implications for the future of bone defect treatments?

The implications for the future of bone defect treatments are significant. The study's findings suggest that prevascularized 3D-printed scaffolds can be used for healing larger bone defects. By combining 3D printing with bioactive hydrogels and cell co-culture, researchers can create constructs that not only provide structural support but also actively promote vascularization and integration with the host tissue. This approach has the potential to revolutionize treatments for large bone defects. This can lead to improved patient outcomes by accelerating the healing process and enhancing the success rate of bone grafting procedures. This could reduce recovery times and improve the quality of life for individuals with bone injuries or diseases.