Professor Zhao Ansha of Southwest Jiaotong University Pioneers 'Implant-Free' Interventional Therapy Using Hydrogel to Fundamentally Address Postoperative Hyperplasia

Blood vessels are the vital channels of the human body, connecting various organs and supplying oxygen and nutrients around the clock. Their importance is self-evident.

However, blood vessels are actually very fragile. Poor lifestyle habits, excessive stress, and air pollution can all trigger vascular diseases. Common conditions include coronary heart disease, cerebrovascular disease, and lower extremity atherosclerotic occlusive disease. Mild cases require long-term medication for control, while severe cases can be life-threatening.

According to the latest released"Report on Cardiovascular Health and Diseases in China 2021"shows that the current number of prevalent cases of cardiovascular disease (CVD) in China is330 million, and the prevalence rate continues to rise. In China, there are 13 million stroke patients, 11.39 million patients with coronary heart disease, and 45.3 million patients with lower extremity arterial disease. Stroke and ischemic cardiomyopathy have become the leading causes of death among patients with vascular diseases in China.

Currently, the most widely used treatment for vascular diseases is percutaneous coronary intervention (PCI). In China, the number of PCI procedures performed solely for coronary heart disease reached an astonishing 915,000 in 2018, and this figure continues to rise.

Professor Zhao Ansha of Southwest Jiaotong UniversityWith over two decades of focus on the research and development of vascular interventional materials, she has identified that current percutaneous coronary intervention (PCI) therapies still present challenges such as high procedural complexity and elevated costs. Most critically, because PCI requires the implantation of stents or balloons from outside the body into the patient, it inevitably causes varying degrees of physical trauma and may even trigger complications. In severe cases, these complications carry the risk of requiring secondary surgeries. Consequently, she decided to develop a non-implantable interventional device to address this issue.

After multiple experiments, she choseHydrogels with Simple Preparation, Ease of Use, Versatile Efficacy, and In Vivo DegradabilityAs an interventional material, we ultimately developed a "high-adhesion hydrogel coating capable of rapidly repairing vascular injury and promoting vascular remodeling," thereby enabling implant-free interventional procedures.

So, why did Professor Zhao Ansha choose hydrogels as her material of choice? With a proven track record in successful technology translation and having completed numerous industry-sponsored projects, how does she plan to navigate the translational pathway for hydrogels?“Sci-Tech China” The 2nd Biomedical High-Value Patent Project Selection ActivityInvitation,VBOrange BureauwithProf. Zhao AnshaEngaged in an in-depth conversation.

To combat vascular diseases, humans made efforts long ago and invented endovascular intervention through continuous attempts.

The first vascular intervention took place in Germany in 1929, when Forssmann proposed the concept of inserting a catheter for angiography and successfully advanced a catheter from his antecubital vein into the atrium on himself. This “whimsical and absurd act” broke through the forbidden zone of vascular surgery.

As times change, various interventional materials have revealed certain drawbacks to varying degrees. Through the filter of time and clinical experience, stent- and balloon-based interventions are now predominantly used in vascular interventional procedures.

The vascular stents currently in clinical use have undergone four generations of innovation compared to the original vascular stents.

The first generation isBare-Metal Stent. The original intention behind the invention of this stent was also very simple: to provide “support.” By supporting and expanding the blood vessel, it helps alleviate the problem of localized vascular stenosis.

However, its drawbacks are quite evident: the material of bare-metal stents can easily irritate blood vessels, causing smooth muscle proliferation and leading to restenosis. This necessitates multiple subsequent surgical interventions for repair, thereby inflicting unnecessary physical harm on patients.

Therefore, during the development of second-generation stents, there was a conscious effort to address the issue of “restenosis,” but no effective solution could fundamentally resolve this problem. Ultimately, researchers decided to attach# Combating Hyperplasiamedications were used for relief, and under the effect of these drugs, the incidence of hyperplasia indeed decreased. From this point on, vascular stents began to gain wider acceptance.

However, subsequent clinical observations revealed that the drug could cause adverse effects, such as damage to endothelial cells on the vascular surface, leading to complications like late-stage thrombosis or endothelial dysfunction. Consequently, research on third-generation stents has focused on modifying the drugs used in second-generation devices.

However, regardless of the generation, the first three generations of stents inevitably cause varying degrees of secondary trauma to blood vessels. To address this critical issue, an increasing number of researchers have begun exploring whether implant-free or short-term implantation strategies can be achieved to minimize unnecessary harm to patients. While some researchers have gradually shifted their focus to biodegradable stents to enable short-term implantation as much as possible, Professor Zhao Ansha has decided to go a step further by achievingPCI Without Implantation。

Professor Zhao Ansha'sSouthwest Jiaotong University: One of the earliest institutions in China to conduct research on cardiovascular materials, and inAdvanced Materials Technology Research FieldIt is also among the best. Therefore, Professor Zhao Ansha’s research group has consistently focused on addressing critical pain points in healthcare and leading the development of the vascular interventional materials industry. They have conducted research on first-, second-, third-, and even fourth-generation vascular stents. This time, they aim to once again lead the industry by pioneering research on implant-free solutions, thereby providing new perspectives for their peers.

Drawing inspiration from polymer materials, they ultimately selected hydrogels—non-toxic, readily biodegradable, and capable of drug loading—for their research. Currently, the hydrogels under investigation have been granted a series of invention patents, and a liquid spray-type adjuvant based on these hydrogels has been developed and entered clinical trials.

Professor Zhao Ansha's Evaluation of Hydrogel Applications“Ushering in the Era of Implant-Free PCI”, but in fact, the advantages of hydrogels go far beyond simply being “biodegradable.”

First, as a hydrophilic polymer material with a network structure, hydrogels possess excellent biocompatibility and ion transport capabilities, and have been widely applied in medical fields such as biomimetic materials and artificial tissues. Professor Zhao Ansha, through literature review and clinical investigation, found thatHydrogels exhibit excellent biocompatibility with vascular tissues., it is embedded and integrated into the inner wall of blood vessels through bonding with tissues, effectively reducing implantation trauma and maintaining good vascular compliance.

Therefore, the use of hydrogels as intravascular interventional materials essentially prevents hyperplasia, thereby addressing the root cause of restenosis.

Secondly,Hydrogels Exhibit Strong Adhesiveness, which can rapidly control hemorrhage following extensive vascular trauma. In cases of severe trauma, such as aortic rupture or penetrating cardiac injuries, massive blood loss poses a significant threat to the patient's life. Under these circumstances, traditional suture-based repair carries a high risk of exsanguination and may even be life-threatening. However, spraying hydrogel onto the affected area can quickly seal the bleeding site, thereby significantly improving the patient's chances of survival.

Additionally,Biomimetic extracellular matrix hydrogels can also induce regeneration of the damaged intima., thereby achieving vascular repair. Specifically, for vessels with atherosclerotic plaques or in cases of aortic dissection, when the hydrogel is delivered to the affected site, its extracellular matrix-mimicking properties actively induce the aggregation of endogenous stem cells to repair vascular lesions, or activate the body’s intrinsic repair potential, thereby promoting superior tissue healing.

Finally, Professor Zhao Ansha also utilized the fact that hydrogels canSustained-Release Drugcharacteristics, nitric oxide (NO) was incorporated into the hydrogel to promote endothelial growth and prevent thrombosis; rapamycin was added to inhibit intimal hyperplasia and prevent stenosis; and statins were included to facilitate intimal repair and prevent atherosclerosis (AS) recurrence, thereby further enhancing the vascular reparative efficacy of the hydrogel.

In summary, the hydrogel developed by Professor Zhao Ansha can “kill multiple birds with one stone,” addressingRepair, Regeneration, and Treatment of Vascular Diseases。

In addition to their high performance, hydrogels are also much easier to handle than stents or balloon implants. Professor Zhao Ansha told VCBeat’s Chengguo Bureau, “Based on our current research on hydrogels, they show promising application prospects in both the diagnosis and treatment of vascular diseases. Most importantly, hydrogels are very convenient to use during surgical procedures. For exposed, superficial vascular injuries, they can beAdministered directly via topical application or injection.. Meanwhile, vascular lesions deep within the body can be treated by advancing a guidewire via arterial puncture into the vessel to reach the specified lesion site for spray application. This convenient procedure can effectively improve surgical success rates, offering greater potential for patient recovery.”

A few years ago, the “vascular stent with functions to regulate intimal hyperplasia and promote endothelial regeneration and repair,” developed by Professor Huang Nan from the same research team as Professor Zhao Ansha, was successfully translated into clinical practice. By 2021, it had been applied in approximately 192,000 patients, marking a successful transition from source-innovation basic research to large-scale clinical application. This valuable experience has also provided Professor Zhao Ansha with insights into the translation of scientific achievements.

Professor Zhao Ansha told VCBeat’s Orange Fruit Bureau: “Professor Huang Nan opted for a one-time technology transfer when commercializing his vascular stent. Approximately three years into the commercialization, data feedback from the partnering manufacturer demonstrated that the stent achieved excellent clinical outcomes. The partner promptly contacted us, expressing interest in further collaboration. However, due to the terms of the one-time transfer agreement and various other factors, we were unable to upgrade the vascular stent and also missed the window for filing international patents—a regret we still hold to this day. Drawing on these experiences, we are particularly keen toSeeking highly specialized partners for long-term collaboration, rather than one-off transfers."This approach will enable our hydrogel to reach the market sooner, while not affecting its future upgrades and replacements."

Overall, Professor Zhao Ansha, our partner, put forward four requirements:Sustainable, specialized, market-savvy, and capable.

In Professor Zhao Ansha’s view, scientific research achievements are never accomplished overnight; they require a prolonged period of meticulous refinement. Therefore, it is preferable for collaborators to maintain long-term partnerships, thereby providing a sustained and stable incubation environment for research outcomes.

Furthermore, scientific achievements are not “static” once developed; researchers can further upgrade and enhance their performance based on clinical data feedback. Therefore, stable, long-term collaborative partners are crucial for subsequent development.

Furthermore, partners must possess a certain level of expertise and understand the application market and potential of hydrogels. The hydrogel currently developed by Professor Zhao Ansha is classified as a Class III medical device, which demands high professional specialization. If collaborators lack understanding in this field, they will naturally fail to appreciate that the research requires an extended period for optimization. This misalignment in expectations would hinder effective communication and significantly compromise the outcomes of the collaboration.

Furthermore, as Professor Zhao Ansha has long been based in the laboratory, there may be informational biases regarding market and clinical needs. Therefore, Professor Zhao also requires partners to integrate market demands, ensuring that scientific achievements directly address market pain points and resolve clinical challenges.

Professor Zhao Ansha stated, “In some of our previous translational experiences, we took quite a few detours. I believe the most critical aspect of collaboration is fostering mutual understanding and working toward a common goal. Currently, our primary expectation is to translate hydrogel technology into clinical applications to address practical challenges, thereby ensuring satisfaction among both patients and society.”