Bi-Tech Medical Solves the Clinical 'Assignment' on Prostate Cancer with an Innovative Hydrogel-Based Radiotherapy Protection Product

According to the American Association for Cancer Research (AACR) “AACR Cancer Progress Report 2023,” from October 1, 2022, to July 31, 2023, the U.S. Food and Drug Administration (FDA) approved 14 novel anticancer therapies, two new optical imaging agents, and 12 new indications for existing (“older”) anticancer therapies. With the rapid development of the biopharmaceutical industry, cancer treatment appears to have reached a new level.

As one of the three traditional pillars of cancer treatment, radiotherapy firmly maintains its position as a first-line therapy for various types of cancer. In terms of clinical application, radiotherapy offers advantages such as being painless, non-invasive, safe, minimally damaging, and broadly applicable, allowing it to play a role throughout the entire course of cancer management. Beyond serving as a palliative option for certain advanced-stage cancers, it is also the preferred primary treatment for malignancies such as nasopharyngeal carcinoma and an effective adjuvant therapy before or after surgery for various other cancers, thereby achieving a synergistic effect where “1+1>2.”

Prostate cancer is one of the most common malignant tumors in the male genitourinary system. With its incidence rate rising year by year, it has become one of the major threats to the health of elderly men. Most puzzlingly, publicly available data show that the five-year survival rate for prostate cancer in China is less than 70%, whereas in Europe and the United States, particularly in the U.S., the five-year survival rate approaches 100%.

“With global medical standards converging to near parity, why do such significant disparities in prostate cancer survival rates persist?” This is one of the research questions posed by hospitals to researchers, and was described by Professor Chen Si, a doctoral supervisor at the College of Materials Science and Engineering, Zhejiang University of Technology, as “a prescribed essay topic assigned by the hospital.”

Since its establishment, Zhejiang University of Technology has demonstrated its distinctive educational philosophy of “upholding the Zhejiang Spirit in education and engaging in interactive development with the region.” “Most of our laboratory projects are highly ‘grounded,’ aiming to directly address real-world problems in industry,” said Chen Si.

In 2015, Chen Si formally established a project team comprising doctoral and master’s students to address clinical needs using polymer materials. However, as early as before 2015, Chen Si and his team had already begun exploring the use of polymer materials to bridge the gap between industry and academia, enabling advanced research findings to be applied in industrial settings. In the course of serving the industry, they often encountered unexpected benefits—“materials developed for Project A might prove useful for Project B.”

In a series of research projects closely aligned with “local industrial needs,” Chen Si gradually adopted the overarching research strategy of “modifying structures to alter material properties, thereby enabling innovative applications,” aiming to bridge the entire chain from fundamental research to industrial commercialization. “After engaging deeply with the industry chain, I realized that a gap still exists between theory and practical application. While a substantial number of papers, research findings, and patents have been published in some highly popular fields, certain bottlenecks remain unresolved in actual industrial applications,” said Chen Si.

Hydrogels represent a typical case in point. As of April 20, 2024, a search for the keyword “hydrogel” in the Google Scholar database yielded 415,000 related publications since 2020; with 28,900 papers already published in 2024 alone, this underscores the rapid advancement of hydrogel research. Nevertheless, translating these achievements into industrial applications still faces numerous challenges.

In terms of functional characteristics, hydrogels exhibit biocompatibility, hydrophilicity, controlled drug release, and intelligent drug delivery, making them ideal carriers for a wide range of applications across industries such as industrial manufacturing, agriculture, and healthcare. Currently, the development of hydrogels is primarily directed toward high performance and multifunctionality, with gelators playing the decisive role.

“The safety and stability of hydrogels are critical to their industrial application. However, the designability of hydrogels often involves physical or chemical changes that are highly sensitive to external environmental conditions. Even minor deviations can compromise the reproducibility of hydrogels, thereby directly affecting their safety in biomedical applications,” said Chen Si. In light of this, Chen Si and his team positioned their development standards and objectives at the level of Class III medical devices. “We must adhere to the most stringent standards for product development.”

Since 2019, the College of Materials Science and Engineering at Zhejiang University of Technology has formally entered into strategic cooperation agreements with multiple hospitals and research institutions, including the Affiliated Hospitals of Zhejiang University School of Medicine, the Hangzhou Institute for Advanced Study of the Chinese Academy of Sciences (CAS), and Zhejiang Provincial People’s Hospital. Through initiatives such as joint research projects, collaborative studies, and co-supervision of graduate students, these partnerships promote interdisciplinary integration. With a focus on medical-engineering cross-innovation, they concentrate on clinical application research and the development of new technologies and products in fields such as novel medical materials, digital healthcare, and biopharmaceuticals. Building on this momentum, Chen Si and his team have advanced significantly in the realm of medical-engineering innovation, culminating in the establishment of Bitai Medical in 2022.

To address the “prescribed topics” set by hospitals, Biotai Medical’s founding team also includes its Chief Scientist, Professor Wang Xu. He serves as Dean of the College of Materials Science and Engineering at Zhejiang University of Technology, Director of the Key Laboratory of Green Plastic Additives and Applications under the China National Light Industry Council, Deputy Director of the Zhejiang Provincial Key Laboratory of Plastics Processing Technology, and Chairman of the Zhejiang Plastics Industry Association. Professor Wang has led or participated in more than 20 national- and provincial-level scientific research projects, including major provincial key scientific and technological breakthrough initiatives, as well as over 30 industry-commissioned projects. He has published more than 150 academic papers, co-authored two monographs, been granted 50 invention patents, and received eight national- and ministerial/provincial-level awards for scientific and technological achievements.

Furthermore, Bitai Medical’s core team comprises talent in two key areas: materials scientists dedicated to innovative breakthroughs, and biology experts and clinicians focused on the clinical frontier.

Worldwide, prostate cancer is one of the most common cancers in men. Data released by the National Cancer Center in 2022 showed that in China, the incidence rate of prostate cancer surpassed that of kidney and bladder tumors in 2016, ranking first among male genitourinary malignancies, with 73,000 new cases and 34,000 deaths. From 2000 to 2016, the average annual increase in the incidence rate of prostate cancer in China was 7.1%, the mortality rate increased by an average of 4.6% per year, and the average five-year survival rate was 69.2%.

Meanwhile, the “Cancer Statistics 2024” report published in CA: A Cancer Journal for Clinicians shows that cancer mortality rates in the United States have been declining year by year. Among these, prostate cancer mortality has decreased by 53% since its peak in 1993, with an average 5-year survival rate reaching 97.4%.

The disparity in the average 5-year survival rates for prostate cancer between China and the United States is attributed to differences in early screening and diagnosis, as well as protective measures associated with radiotherapy and surgery. The standard treatment options for prostate cancer are radical prostatectomy or radiotherapy; both are considered clinically equivalent in efficacy, yet they differ in their side effect profiles. Side effects of radical prostatectomy include erectile dysfunction and urinary incontinence, whereas the primary adverse effect of radiotherapy is radiation-induced toxicity to the rectum.

“Based on our clinical observations and feedback from physicians, there is currently a lack of devices or biomaterials capable of protecting surrounding tissues such as the rectum during radiotherapy for prostate cancer. This represents the most significant difference between our approach and clinical prostate cancer treatment in the United States,” said Chen Si. Years ago, radiation oncologists already began considering the use of “spacing” techniques to reduce the risk of radiation-induced damage to surrounding tissues during radiotherapy.

Balloons, hyaluronic acid, and collagen injections are commonly used “spacer” materials that have been proven to reduce radiation dose to the rectum during radiotherapy; however, they have limitations such as the need for secondary surgical removal, short duration of effect, insufficient stability, or uneven distribution.

In 2010, a polyethylene glycol-based hydrogel system (SpaceOAR™ System) received CE certification and was launched in multiple countries and regions, including the United States and the European Union. SpaceOAR™ hydrogel is a sterile, single-use, injectable, absorbable polymer hydrogel that provides approximately 25% radiation attenuation. By injecting SpaceOAR™ between the prostate and the rectum, it separates or displaces the rectum from the radiation field during radiotherapy for prostate cancer, thereby reducing radiation-induced rectal injury and significantly improving patients’ quality of life after treatment. Regrettably, this advanced biomaterial only initiated its “pilot implementation” program in China at the end of 2022 and has not yet been widely adopted in clinical practice; furthermore, no domestically approved comparable products are currently available in China.

Hydrogel materials are considered the most ideal spacer materials at present due to their customizable structural design, good biocompatibility, injectability, and degradability. In the clinical application of prostate radiotherapy, ensuring the stability and reproducibility of hydrogels is crucial. Public information indicates that SpaceOAR™ utilizes a PEG-based hydrogel material, which has certain limitations in production volume due to requirements related to its mechanical and biological properties.

“We aim to develop hydrogels, but we must identify a raw material that is widely available, proven safe, and commonly accessible,” said Chen Si. Based on this principle, Bitai Medical has developed hydrogel materials by modifying natural polysaccharides, and thereby created a tumor radiotherapy protection product featuring “spacer protection–multimodal imaging–precise degradation”—the Prostate Cancer Radiotherapy Protection Gel (Hydrogel Rectal Spacer). According to the company, Bitai Medical’s natural polysaccharide hydrogel ensures stability while enabling controlled degradation and spacer protection functionality. “Experiments have shown that it currently achieves approximately 30% radiation attenuation.”

Bitai Medical’s independently developed first tumor radiotherapy protection product featuring “spacer protection–multimodal imaging–precise degradation”—the prostate cancer radiotherapy protection gel (hydrogel rectal spacer)—employs core technologies such as dual interpenetrating network formulation design and contrast agent molecular structure design, thereby overcoming current technical bottlenecks of spacer materials, including the lack of personalized customization, the pronounced contradiction between “spacer protection and controlled degradation,” and the absence of long-term imaging throughout the product’s lifecycle.

Specifically, radiotherapy for prostate cancer typically involves multiple fractions over a period of 2–3 months. After one or two treatment sessions, the radiation field and dosage need to be adjusted based on the patient’s therapeutic response, requiring repositioning for subsequent rounds of radiotherapy. “During this repositioning process, we achieve multimodal imaging by incorporating long-acting contrast agents and leveraging molecular structure design of contrast media. This approach facilitates rapid and convenient clinical localization of lesions, while also enabling controlled drug release and monitoring,” explained Chen Si.

“Meanwhile, Biotay has designed this long-acting contrast agent to cover the entire lifecycle of radiotherapy. ‘We achieve material-lifecycle matching through molecular structure design of the contrast agent, ensuring that imaging visibility is fully synchronized with material degradation and metabolism, thereby covering the entire course of radiotherapy,’ added Chen Si.”

According to Bitai Medical, the modified material has currently been tested in both small and large animals, with data indicating “highly ideal” spacer stability and long-term imaging properties. “Additionally, we have encountered some unexpected benefits—in large animal studies, this material was proven to possess multimodal imaging capabilities, enabling its simultaneous use for both ultrasound and CT imaging.”

In addition to its hydrogel product developed for radiotherapy in prostate cancer, Bitai Medical is also developing a hydrogel product for target volume marking in breast cancer. Clinically, patients with early-stage breast cancer often opt for breast-conserving surgery. To reduce the risk of local recurrence and distant metastasis postoperatively, these patients require adjuvant radiotherapy after breast-conserving surgery to prevent recurrence. “This postoperative radiotherapy typically involves whole-breast irradiation with a focus on the target volume, necessitating target volume marking,” said Chen Si.

Currently, clinical practice primarily relies on the intraoperative implantation of metallic clips to localize the target area. These clips remain in the patient’s body for life, as no secondary surgery is performed to remove them. In light of this consideration, Bitai Medical has developed a novel target-marking material aligned with clinical needs. This material features a degradation profile that matches the therapeutic timeline, enabling effective target localization while offering full lifecycle biodegradability.

Furthermore, for the clinical treatment of breast cancer, Bitai Medical is also working on material modifications to achieve functions such as radiosensitization and fat grafting, with a particular focus on radiation protection for head and neck cancers.

Precise positioning, precise drug delivery, and precise control of degradation time represent Baitai Medical’s triple understanding of “precision” in its spacer protection materials. Addressing unmet clinical needs is the original intention and mission behind Baitai Medical’s material design. “Medical-engineering collaboration and coordinated innovation serve as a new channel to accelerate the translation of scientific achievements into practice, and also as the ‘shortcut’ to truly meeting clinical needs,” said Chen Si.