For patients suffering from traumatic injuries that leave behind “volumetric” gaps — where significant bone and blood vessels are lost — the clock is always ticking. Without a nearby blood supply, cells in the center of a large injury cannot survive, often leading to permanent tissue loss or failed grafts.
A team of eight scientists at The University of Texas at San Antonio has discovered a potential “perfect recipe” to address this challenge. By blending two natural proteins found in the human body, the researchers created a specialized scaffold that allows bone and blood vessels to grow simultaneously at an accelerated rate.
The study, published in the journal Biomaterials Advances, identifies a 50:50 ratio of collagen and fibrin as the ideal environment for tissue repair.
The Lego blocks of healing
The technology relies on what scientists call interpenetrating polymer networks, or IPNs. In simpler terms, it is a microscopic support structure where different materials are entangled to create a stable foundation for new growth.
“An IPN network is two things that are entangled like a giant mess of Legos,” said Teja Guda, PhD, the Jacobson Distinguished Professor of Innovation and Entrepreneurship in the Department of Biomedical Engineering and Chemical Engineering at UT San Antonio and the study’s corresponding author. “We are leaving all the building blocks there and letting the cells build whatever Lego structure they like the most.”
In this biological “Lego” set, one material is fibrin, the protein the body uses to form blood clots immediately after an injury. The other is collagen, the primary structural protein found in bones and other tissues.
Seeding the scaffold with MVFs and MSCs
To turn these protein gels into living tissue, the research team “seeded” the hydrogels with two critical types of biological starters: microvascular fragments (MVFs) and mesenchymal stem cells (MSCs). The MVFs have the capacity to grow into blood vessels, while the MSCs can, with the right environmental cues, grow into bone.
The researchers integrated these components by mixing the living MVFs and MSCs directly into the liquid protein solution before it underwent gelation. This 3D encapsulation ensured the cells were suspended throughout the entire depth of the scaffold rather than just sitting on the surface.
Balancing blood and bone
Standard medical treatments for severe bone loss typically involve autografts, where bone is harvested from another part of the patient’s body, or allografts, which use processed bone from a donor. These traditional grafts often fail to integrate because they lack an immediate blood supply to nourish the new tissue. Without rapid vascularization, the transplanted bone can become necrotic, leading to a high rate of clinical failure in complex trauma cases.
The challenge for UT San Antonio researchers was finding the right balance between the two proteins to support both blood vessel and bone regeneration. Fibrin is excellent at recruiting the cells needed to form blood vessels, a process called angiogenesis. Collagen provides the mechanical strength needed to guide the development of bone, or osteogenesis.
“Whenever you have an injury where you are losing volume, you not only lose the tissue itself, but you’re also losing blood vasculature,” said Gennifer Chiou, a postdoctoral fellow at UT San Antonio and the study’s lead author. “We’re looking at how we can regenerate both the tissue and the vessel itself within specifically bone tissue.”
The team tested five different ratios of the two proteins. They found that while gels with more fibrin supported faster vessel sprouting, they lacked the stability needed for long-term bone growth. Conversely, high-collagen gels were too stiff for vessels to penetrate easily.
The 50:50 blend struck an ideal balance. The MVFs were able to sprout and branch out into a robust, interconnected network. Simultaneously, the MSCs developed in a stable environment, expressing the specific genetic markers needed to mature into bone-forming cells. This dual-growth approach ensures that as the new bone forms, it is continuously supplied with the blood and nutrients it needs to remain viable.
From the lab to the clinic
Because the materials used in the study — collagen, fibrin and the patient’s own blood vessels — are all naturally occurring in the body, the researchers believe the technology faces fewer regulatory hurdles than synthetic alternatives.
“There is almost nothing new in our material,” Guda said. “It’s your collagen, it’s your blood vessels, it’s your fibrin. The end goal is to provide evidence that will guide how clinicians think about healing wounds.”
The team hopes to proceed to preclinical trials in the near future, which will provide further support for the treatment to one day become standard practice.
Other authors on the paper include Sarah Stagg, Gabriela Gonzales, Liliana Danford, Isaiah Arredondo, Rena Bizios and Joo L. Ong.
