Peking Union Medical College Hospital Licenses Janus Supramolecular Hydrogel Technology for Wet Tissue Adhesion to Jiangsu Renguan Medical in RMB 620,000 Deal

Recently, Peking Union Medical College Hospital released a public notice on the transformation of its scientific and technological achievements, proposing to transfer the ““An Adaptive Janus Supramolecular Hydrogel, Its Preparation Method, and Its Application as an Adhesive for Wet Tissue Surfaces”The relevant patent portfolio is licensed to Jiangsu Renguan Medical Technology Co., Ltd. for use, with a total licensing fee of RMB620,000 yuan. The inventors of this patented technology are Professor Zhao Yu and his team from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.

Transferee of This Patent TechnologyJiangsu Renguan Medical Technology Co., Ltd., is an innovative enterprise focused on the fields of medical biomaterials and surgical instruments. Rooted in the life sciences and healthcare sectors, the company is positioned around the core mission of “promoting the clinical translation of cutting-edge medical technologies and addressing pain points in clinical treatment.” It is dedicated to the research, development, production, and industrialization of medical adhesives, tissue repair materials, and supporting diagnostic products.

The present invention disclosesAn Adaptive Janus Supramolecular Hydrogel, Its Preparation Method, and Application as an Adhesive for Wet Tissue Surfaces.This hydrogel features an integrated structure with two asymmetric sides: an adhesive side and an anti-adhesive side. It is suitable for applications in wet tissue surface adhesion.

Cerebrospinal fluid leakage caused by dural defects is a common complication in spinal and neurosurgical procedures. It not only has a high incidence rate but also poses significant risks, potentially leading to paralysis or even death, thus representing a major challenge in current clinical practice. Existing clinical strategies primarily rely on suturing; however, surgical suturing is technically demanding, often results in suboptimal closure, and is prone to causing needle-hole leaks and tissue adhesion.

Commonly used adhesives on the market, such as fibrin-based and cyanoacrylate adhesives, suffer from issues including poor adhesion efficacy and inadequate safety. Meanwhile, existing patch materials, such as bovine pericardial patches, animal-derived collagen, polytetrafluoroethylene (PTFE), and polylactic acid (PLA), require surgical suturing or adhesive sealing. These materials are associated with problems such as unstable wet adhesion, spinal cord nerve compression due to swelling, poor mechanical property matching with native tissues, and tissue adhesion. Consequently, they fail to meet the high standards required for dural defect repair in spinal and neurosurgical procedures.

Ideal Dural Repair MaterialsIt should exhibit stable wet adhesion, mechanical properties matching those of native tissues, controllable mass and volume, as well as functions that promote repair and prevent tissue adhesion. In existing technologies, hydrogel materials have been applied in these areas; however, there is currently a lack of biomedical materials that simultaneously possess extracellular matrix-like structural characteristics, excellent biocompatibility, tunable and reversible adhesive strength, low swelling ratio, and the ability to adhere stably to wet tissue surfaces while preventing tissue adhesion. Therefore, the academic community has been continuously striving to develop materials that better meet clinical needs.

For example,South China University of TechnologyA has been publicly disclosedTechniques for Preparing the Anti-Adhesive Layer of Janus HydrogelsIn this technique, acrylamide is used as the monomer, with the crosslinker, photoinitiator, and monomer dissolved in water, and polymerization is initiated by ultraviolet (UV) irradiation. Subsequently, acrylic acid is used as the monomer, which is dissolved in water along with the crosslinker, photoinitiator, and lithium magnesium silicate (Laponite). The solution is cast onto the surface of an anti-adhesive layer, and polymerization is again initiated by UV irradiation to fabricate a Janus hydrogel adhesive. However, the use of crosslinkers increases the toxicity of this hydrogel material.

The fabrication process involves casting the prepolymer solution onto the hydrogel surface followed by photopolymerization. The resulting hydrogel possesses a composite structure rather than an integrated design, leading to issues such as insufficient interfacial strength and poor wet adhesion. Furthermore, due to the predominant use of the hydrophilic monomer acrylic acid, the prepared hydrogel exhibits a high swelling ratio.

Zhejiang University of TechnologyDisclosed aPreparation Method of Novel Janus Hydrogel Adhesives, this method involves copolymerizing methacrylated sodium hyaluronate with sulfobetaine-type zwitterionic monomers under UV irradiation, followed by immersion in the photoinitiator α-ketoglutaric acid. Finally, an aqueous solution of acrylic acid and N-hydroxysuccinimide acrylate monomers is coated onto the hydrogel surface and polymerized under UV light. However, due to the adoption of a surface-coating strategy, the resulting Janus hydrogel does not possess an integrated structure and suffers from issues such as low mechanical strength (approximately 0.1 MPa), high swelling ratio, and poor wet adhesion, making it difficult to meet the clinical application requirements for dural defect repair.

Zhejiang UniversityA team employed cetyltrimethylammonium bromide (CTAB) to emulsify the hydrophilic monomer acrylic acid and the hydrophobic monomer lauryl methacrylate (LMA), followed by the addition of polyphosphazene functionalized with phenylboronic acid and quaternary ammonium groups, along with natural polyphenols. Finally, polymerization was initiated using a photoinitiator to prepareJanus Hydrogel. However, the emulsifiers used pose toxicity concerns, and the introduction of natural polyphenols induces an inhibition effect, resulting in incomplete monomer polymerization, which further increases toxicity and hinders application in vivo. Furthermore, the mechanical properties and wet adhesion strength of this hydrogel remain to be improved.

Existing hydrogel adhesive materials not only exhibit low wet adhesion strength but also undergo water absorption and swelling. Furthermore, most Janus hydrogels are fabricated via simple casting and lamination rather than as an integrated structure, leading to unstable interfacial bonding between the adhesive and anti-adhesive layers. This results in issues such as easy detachment in physiological fluid environments and tissue adhesion. Consequently, while these materials are suitable for applications like skin wound healing, they are difficult to apply in the repair of dural defects.

To address the aforementioned technical challenges, the R&D team proposedA Janus Hydrogel with an Adhesive Surface and an Anti-Adhesive Surface, withAddressing Dural Repair in Wet Environmentscore needs.

The team-developed adaptive Janus supramolecular hydrogel, through systematic innovations in structural design, raw material selection, and preparation processes, creates a novel medical material that combines stable adhesion, anti-adhesion properties, high biocompatibility, and excellent mechanical performance.

1. Integrated Asymmetric Structural Design

The core innovation of this hydrogel lies inBreaks Through the Limitations of Traditional Janus Hydrogels' "Simple Casting Composite" Approach, successfully establishedAn integrated interpenetrating network structure with seamless fusion of adhesive and anti-adhesive surfaces。Adhesive SurfaceIt is synthesized by copolymerizing a first monomer (such as polyethyleneimine, polylysine, etc.), a second monomer (such as acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid, etc.), and N-isopropylacrylamide (NIPAM), achieving robust adhesion to wet tissue surfaces through hydrogen bonding, ionic interactions, and hydrophobic interactions;Anti-adhesion SurfaceZwitterionic monomers (such as DMAPS and SBMA) are employed to form the structure via one-sided solvent-induced polymerization, endowing it with excellent anti-protein adhesion and anti-tissue adhesion properties. The two layers are tightly connected through strong ionic interactions rather than simple physical lamination, thereby thoroughly addressing the critical issues of insufficient interfacial strength and prone-to-detachment in physiological fluid environments associated with traditional composite hydrogels. This achieves the synergistic integration of the two core functions: “stable adhesion” and “anti-adhesion.”

2. Non-toxic Adjuvant Formulation System

The R&D team is atRaw Material SelectionAlways on topAdhere to the “Safety First” Principle, innovatively eliminating toxic auxiliaries commonly used in traditional hydrogel preparation, such as crosslinking agents and emulsifiers, and achieving network crosslinking and structural stability solely through supramolecular interactions between monomers (e.g., hydrogen bonds, ionic bonds, and hydrophobic interactions). Meanwhile, low-toxicity or non-toxic photoinitiators, such as α-ketoglutaric acid and 2,2-diethoxyacetophenone, were selected to further reduce the biological risks of the material. Experimental validation results showed that after co-culturing the hydrogel with fibroblasts for 1 to 5 days, cell proliferation viability exhibited no significant difference compared to the control group; after implantation at the rat dural mater for 14 days, tissue sections showed no obvious inflammatory response, and Masson’s trichrome staining confirmed its favorable in vivo biocompatibility, providing a core guarantee for clinical application safety.

3. Ultra-low Swelling Ratio and Excellent Mechanical Properties

To address the issues of traditional repair materials, such as excessive swelling rates that easily compress nerves and mismatched mechanical properties that lead to breakage, this hydrogel optimizes monomer ratios and structural design,Achieves a perfect balance between ultra-low swelling ratio and high strength-toughness mechanical properties. Its swelling ratio is less than 2%, significantly outperforming existing hydrogel products (which typically exceed 10%), thereby effectively preventing secondary injuries such as spinal cord nerve compression caused by postoperative water absorption and expansion. Mechanical test results show that the hydrogel has an elongation at break of up to 600%, a tensile strength at break exceeding 2 MPa, and an adhesion strength to wet tissues such as pig skin of over 70 kPa. Moreover, it maintains stable performance after 10 cyclic tests under 400% tensile deformation. In addition, the material possesses dynamic viscoelasticity and self-healing capabilities similar to those of the extracellular matrix, enabling it to adapt to the deformation and movement of internal tissues, which significantly enhances the durability of the repair effect.

4. Temperature-responsive design to enhance adhesion adaptability in wet environments

Hydrogels through the introduction ofN-Isopropylacrylamide(NIPAM) achieves precise temperature-responsive characteristics, with its phase transition temperature optimized through copolymerization to perfectly match the human physiological environment (37°C). At body temperature, hydrogen bonds between the hydrogel polymer chains break, endowing the material with excellent flexibility and mobility. On one hand, it significantly enhances adhesion stability in wet environments by displacing water at the tissue–hydrogel interface through hydrophobic aggregation effects; on the other hand, it better conforms to the irregular topography of tissue surfaces, improving mechanical matching. Experiments have confirmed that this hydrogel can rapidly achieve instantaneous sealing of wet tissue defects (for example, in rabbit gastric leakage models, leakage ceased immediately upon adhesion), and it demonstrates stable adhesive capacity to various wet tissues, including the heart, liver, spleen, lung, kidney, and dura mater, indicating broad application potential.

5. Simple and Controllable Preparation Process

Compared with the cumbersome preparation process of traditional hydrogels, the preparation method provided by this patent has significant advantages such as convenient operation, mild conditions, and controllable costs. The entire processTwo-Step UV Polymerization(wavelength 350–405 nm, light intensity 50–200 mW/cm²), without the need for complex equipment or stringent reaction conditions; all raw materials used are commercially available and readily accessible, and the monomer ratio (first monomer : second monomer : NIPAM : third monomer = 1 : (0.8–2) : (0.05–0.3) : (0.5–1)) can be flexibly adjusted to meet the performance requirements of different tissue repair applications. The streamlined preparation process and low raw material costs significantly lower the barriers to industrialization, laying a solid foundation for large-scale production and clinical adoption of the material.

This study achieves a comprehensive breakthrough in the technical bottlenecks of existing medical adhesive materials—such as wet adhesion stability, interfacial bonding strength, biocompatibility, and mechanical matching—through multidimensional innovations in structure, formulation, and function. It not only provides an ideal solution for dural defect repair but can also be extended to the adhesive closure of injuries in various wet tissues, including the intestine, liver, lung, and stomach.

In the highly sought-after field of wet tissue adhesion, multiple companies have initiated R&D and product commercialization efforts focused on medical adhesives, hydrogel repair materials, and other related areas, forming“Iteration of Traditional Materials + Breakthroughs in Innovative Technologies”of a landscape characterized by diverse and competitive dynamics.

Currently, similar products on the market are primarily concentrated in the field of surgical repair, with technical approaches including chemical adhesives, natural biological patches, and hydrogel materials. Different companies have their own focuses in terms of R&D progress and product positioning, jointly driving wet tissue adhesion technology toward safer and more precise directions.

withBeijing Yilanbei Biotechnology Co., Ltd.developed by domestic companies represented by“n-Butyl α-Cyanoacrylate Tissue Adhesive”Approved for hemostatic sealing of skin and small blood vessels. Although such products are easy to handle and exhibit strong initial adhesion, their rigid polymer networks are prone to brittle fracture in moist environments, resulting in insufficient long-term wet-adhesive stability. Furthermore, their degradation products possess certain cytotoxicity, rendering them unable to meet the repair requirements of dynamic, sensitive tissues such as the dura mater; consequently, they are currently primarily used for the management of superficial wounds.

In the field of natural biological patches,Beijing Bairen Medical Technology Co., Ltd.of"Bovine Pericardial Biological Patch"It has been widely applied in the repair of tissue defects in neurosurgery and cardiovascular surgery. This product is processed using decellularization technology and glutaraldehyde cross-linking, offering excellent mechanical properties and good biocompatibility, with extensive clinical application experience.

In the Field of Hydrogel Innovation,Companies are actively promoting product development by leveraging their unique technological approaches. For example,Guangzhou Medprin Regenerative Medical Technologies Co., Ltd.R&D"Artificial Dural (Spinal) Patch"(Trade name: Neurolon®), manufactured using poly(lactic-co-glycolic acid) (PLGA) electrospinning technology, features biodegradability and mechanical properties similar to human tissue, and has been successfully applied in clinical dural repair.

Some emerging companies are actively exploring the application potential of Janus-structured hydrogels, for exampleShenzhen New Industries Biomedical Engineering Co., Ltd.Previously conducted"Double-Layer Photocurable Hydrogel"Preliminary studies. Such systems typically employ a stepwise fabrication process, with interfacial bonding primarily relying on physical interactions; consequently, they impose higher demands on structural stability in long-term physiological fluid environments. In some formulations, chemical crosslinking agents (e.g., N,N'-methylenebisacrylamide) are introduced to enhance network strength, but their biosafety must be comprehensively evaluated in the context of specific application scenarios.

It is worth noting that,In the field of high-end moist tissue repair,Foreign-invested enterprises are actively laying out related products.Baxter International Inc.of"Fibrin Sealant"The product has successfully entered the Chinese market and obtained dual certification from the FDA and NMPA. It is suitable for various clinical scenarios, including dural defect repair and hemostasis in liver surgery. The product forms a gel through the enzymatic reaction between fibrinogen and thrombin, mimicking the physiological hemostatic process to achieve tissue adhesion. However, since its mechanism of action relies on the patient’s own coagulation system, the adhesive effect may vary depending on individual coagulation status. Additionally, the product requires intraoperative mixing of two components at the point of care, imposing certain requirements on operational procedures. Reportedly, Baxter is developing a “fibrin–hydrogel composite system” designed to combine the biological activity of fibrin with the mechanical stability of hydrogels; related products have entered Phase II clinical trials.