Sun Yat-sen University to Transfer Patent for Obesity-Associated Knee Osteoarthritis Animal Model to Shenzhen Jingcheng Life Science for RMB 500,000
Recently, Sun Yat-sen University released a public notice on the conversion of scientific and technological achievements, indicating that the university plans to“Method for Establishing an Animal Model of Knee Osteoarthritis in Obese Populations and Its Application”The relevant patents were transferred to Shenzhen Jingcheng Life Sciences Co., Ltd. for use, with a transfer fee of500,000 yuan. The inventors of this patent areProfessor Wang Jiali and His Team。
Image from the official website of Sun Yat-sen University
The assignee of this patent is Shenzhen Jingcheng Life Sciences Co., Ltd., a company focused on the fields of biopharmaceuticals and regenerative medicine, with3D Printing Technology for Bioactive Degradable Bone Repair Materialsas the core, providing coverage across“R&D + Clinical Translation + Product Supply”full-chain services, with products covering areas such as magnesium-containing degradable polymer bone repair materials.
The core of the present invention is to construct a murine model that closely mimics the pathogenesis and disease progression of knee osteoarthritis in clinically obese populations, by combining a high-fat diet with uphill wheel running exercise of specific intensity. This approach also enables the precise establishment of models representing the early, middle, and late stages of the disease, thereby providing a key experimental platform for research on obesity-related knee osteoarthritis.
As a highly prevalent chronic degenerative joint disease, knee osteoarthritis has obesity as its core risk factor. Among the more than 400 million patients worldwide, China accounts for 100 million, with 40% of them being obese patients. However, research on knee osteoarthritis in the obese population has long faced“Low model fidelity, inaccurate disease progression simulation, and hindered research on pathogenesis”the triple dilemma, which severely constrains the exploration of pathogenesis and the research, development, and translational application of therapeutic regimens.
Clinical Knee Osteoarthritis in the Obese Population Due to“Increased weight load on joint stress + systemic/local inflammation”Dual-pathogenesis disease mechanisms lack suitable experimental models for precise investigation of their pathological progression; existing methods fail to recapitulate the true disease course, posing a core obstacle to the development of related therapies.
From the perspective of model construction, existing animal models of osteoarthritis have formedSpontaneous Models and Artificially Induced ModelsTwo major systems exist, yet neither meets the research needs for knee osteoarthritis in obese populations. Spontaneous obesity models induce osteoarthritis slowly through diet-induced obesity, resulting in an excessively long modeling period that fails to support efficient scientific research. Artificially induced models, such as those based on surgical intervention or pure mechanical force, can rapidly cause joint pathological changes; however, they do not incorporate the core pathogenic factors of obesity. Consequently, they are significantly inconsistent with the pathogenesis and disease progression observed in obese individuals, which are driven by weight bearing and inflammatory responses, rendering research findings derived from these models lacking in clinical translational value. Furthermore, wear-and-tear knee osteoarthritis models focus on high-intensity exercise populations, whose etiologies differ entirely from those of obese individuals, thus failing to provide effective references for research on obesity-related knee osteoarthritis.
At the level of disease progression research, the pathological features of knee osteoarthritis differ significantly across its early, middle, and late stages.Precision Phased ModelIt is key to exploring the patterns of disease progression and developing stage-specific treatment regimens; however, existing models fail to achieve controllable simulation of the disease course. Most models can only establish single-stage osteoarthritis models and lack a unified, standardized protocol for model establishment. Consequently, they struggle to accurately recapitulate the progressive pathological process of knee osteoarthritis in obese populations—from mild cartilage damage to complete destruction, and from local synovial inflammation to systemic inflammatory responses. This limitation prevents researchers from clarifying the core pathogenic mechanisms at different disease stages, thereby leaving the development of stage-specific interventions and treatment strategies without clear direction.
Furthermore, existing models still suffer from“Evaluation System Misalignment and Inefficient Model Establishment”These issues further exacerbate the research challenges. Some models have failed to establish a comprehensive evaluation system tailored for knee osteoarthritis in obese populations, focusing solely on articular cartilage damage while overlooking key pathological indicators such as obesity-induced changes in systemic inflammatory factors and loss of cartilage matrix components. Consequently, these models cannot fully validate their effectiveness. Meanwhile, traditional modeling protocols lack standardized design, resulting in inconsistent training outcomes in experimental animals. This leads to poor model reproducibility and low data reliability, which not only increases research costs but also hinders the mutual validation of findings across different studies, thereby impeding the overall advancement of research on knee osteoarthritis in obese individuals.
It is precisely the industry pain points in research on knee osteoarthritis in obese populations—namely, “low model fidelity, inaccurate simulation of disease progression, and inefficient model establishment”—that have driven Professor Wang Jiali’s team at Sun Yat-sen University to undertake targeted technological breakthroughs. The core advantages of their newly developed patented technology, “Method for Establishing and Applying an Animal Model Simulating Knee Osteoarthritis in Obese Populations,” lie in"Developing a Novel Modeling Solution Based on Clinical Mechanism Alignment and Precise Disease Progression Control"FromFrom Model Design and Process Standardization to Model ValidationAchieve multi-dimensional innovation to fundamentally overcome the limitations of traditional animal models of osteoarthritis, which fail to reflect the clinical features of obesity and cannot simulate disease progression in stages.
This technology was firstModel FitAchieve breakthrough innovation—breaking through the bottleneck of existing models that fail to incorporate the core pathogenic factors of obesity,First to combine high-fat diet-induced obesity with uphill running wheel-based strength training, precisely recapitulating the clinical pathogenesis of knee osteoarthritis in obese populations.Traditional models either induce osteoarthritis slowly through diet-induced obesity or cause joint injury via surgery or purely mechanical forces; neither approach can recapitulate the pathological process of articular cartilage damage in obese individuals, which results from the dual effects of “increased joint loading due to weight gain” and “systemic/local inflammation.”
In this patent, a standard obesity model is first established by feeding mice a high-fat diet for 8–12 weeks until their body weight exceeds that of normal mice by more than 20%. Subsequently, uphill treadmill running is employed to increase knee joint stress, thereby simulating the alterations in joint biomechanics under obese conditions. This approach closely aligns with the etiology and pathology of knee osteoarthritis in clinical obese patients, thus enhancing the clinical translational value of the research findings.
At the level of disease course simulation, this technology achievesPrecise Staging for Early, Middle, and Late Stages, addressing the industry-wide challenge that traditional models cannot controllably simulate the progression of diseases.
First,By designing standardized exercise cycles, the duration of formal uphill treadmill running is precisely aligned with disease stages:A 2-week formal exercise regimen establishes an early-stage knee osteoarthritis model, a 4-week regimen establishes a mid-stage model, and an 8-week regimen establishes a late-stage model. This approach accurately recapitulates the progressive pathological process, ranging from mild cartilage defects and fissure formation to complete cartilage destruction and subchondral bone exposure.
Second, a one-week adaptive exercise period was implemented, during which the treadmill speed for the model mice was increased daily by 5 rpm from 0 rpm to 25 rpm.Ensure Consistency in the Training Outcomes of Laboratory Animals, thereby avoiding model bias caused by individual differences and enhancing the stability and reproducibility of model features across different disease stages, thus providing a precise experimental platform for exploring the patterns of disease progression and developing stage-specific intervention strategies.
Furthermore, this technology possesses practical applicability inSimple and Efficient, with a Comprehensive Evaluation Systemsignificant advantages. In terms of the modeling protocol, the patent employs mice as the model animals, selecting common experimental strains aged 4–8 weeks. The modeling steps are standardized and easy to perform, requiring only five consecutive days of wheel-running exercise per week. Compared with spontaneous obesity models, this approach substantially shortens the modeling duration, thereby reducing both the time and economic costs associated with scientific research. In terms of model validation,Established a comprehensive evaluation system integrating serum testing, histological staining, and multi-criteria scoring:The extent of systemic inflammation was assessed by measuring serum TNF-α levels. Synovial inflammation, cartilage damage, and proteoglycan loss were evaluated through hematoxylin and eosin (HE), safranin O-fast green, and toluidine blue staining, respectively. Quantitative assessment was performed using three established scoring systems: Pelletier, OARSI, and Mankin. Additionally, immunohistochemical staining for type II collagen was employed to detect damage to the core structural components of cartilage. This multi-dimensional approach validated the effectiveness of the model, thereby ensuring its scientific rigor and reliability.
Meanwhile, the modeling methodology of this technology can be extended to other experimental animals such as rats and rabbits, offering broad applicability. It lays a solid foundation for investigating the pathogenesis of knee osteoarthritis in obese populations and for developing therapeutic agents and intervention strategies, thereby holding significant value for industry-wide adoption.
Currently, in response to the core needs of research into the pathogenesis of osteoarthritis and the development of therapeutic drugs,Animal ModelsAs a key experimental carrier, a diversified technological layout has been established, with various solutions centered around“Modeling Mechanisms, Disease Course Replication, and Applicable Scenarios”Differentiated development, whereinSpontaneous Models, Surgically Induced Models, Chemically Induced Modelsas the current mainstream technical pathway, while dedicated models focusing on the obese population are still in the stage of technological breakthrough.
Shougang Hospital Co., Ltd.R&DTechnologies for Animal Models of Knee Osteoarthritis and Atherosclerosis Comorbidity, this technologyPioneering the “Metabolic-Mechanical Dual-Drive” Modeling StrategyUsing 6- to 8-week-old male ApoE⁻/⁻ mice, a synergistic model of knee osteoarthritis and atherosclerosis was established through a sequential protocol consisting of a 2-week high-fat diet (HFD), modified Hulth surgery, and continued HFD feeding for 10–14 weeks. The HFD, containing 21% animal fat and 0.15% cholesterol, induced lipid metabolism disorders. The surgical procedure precisely transected the knee ligaments and resected 50–60% of the medial meniscus to create local mechanical instability. Model validation was performed via X-ray detection of osteophytes, aortic lipid plaque staining, and serum NLRP3/IκBα measurements. A highly stable comorbidity model was obtained within 12 weeks, providing a standardized platform for investigating comorbidity mechanisms and screening dual-target therapeutics.
The First Affiliated Hospital of Soochow UniversityDevelopedSynovial Macrophage-Regulated Photothermal Conversion Platform TechnologyThis technology constructs an M2 macrophage membrane-coated black phosphorus/selenium-carbon (M2-BPSeC) photothermal nanoplatform, integrating the triple functions of targeted delivery, precise thermal control, and immune remodeling. Through a three-step process comprising “black phosphorus nanosheet preparation + in situ loading of selenium-carbon quantum dots + M2 macrophage membrane coating,” it achieves specific enrichment in synovial macrophages. Under 808 nm near-infrared laser irradiation, the temperature can be precisely controlled at 42 ± 0.5°C, inhibiting M1 macrophage polarization and promoting M2 phenotype transformation, thereby alleviating cartilage degeneration. In vitro experiments confirm its ability to inhibit cartilage matrix degradation; in vivo, intra-articular injection combined with laser irradiation significantly improves the pathological state of osteoarthritis, providing an integrated targeted-thermal-immune therapeutic strategy for disease treatment.
China Academy of Chinese Medical SciencesDeveloped byPostmenopausal Osteoporosis and Knee Osteoarthritis Comorbidity Model TechnologyThis technology focuses on the comorbidity characteristics of middle-aged and elderly women. Using 10–12-month-old female Sprague-Dawley (SD) rats, postmenopausal osteoporosis was induced through a combination of GnRH agonist injection, low-calcium diet feeding, and oxidative stress stimulation. Rats meeting the eligibility criteria—defined as a ≥15% decrease in bone mineral density and a ≥10% reduction in trabecular bone—were selected. Subsequently, arthroscopic minimally invasive surgery was performed to tear the medial meniscus of the knee joint, followed by implantation of PLGA sustained-release microspheres loaded with IL-1β. Progressive weight-bearing training was conducted for 8–12 weeks postoperatively. Assessments of cartilage status, inflammation, bone metabolism, and functional outcomes were performed at 8 and 16 weeks after model establishment. The model qualification rate reached 90%, accurately recapitulating the comorbid progression of “estrogen deficiency–bone loss–joint injury,” thereby providing a highly relevant experimental tool for targeted drug development.