Intelligent Manufacturing for Osteoarthritis Organoids

Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies are still lacking. Organoid technology, in which stem cells or progenitor cells self-organise into miniature tissue structures under three-dimensional (3D) culture conditions, provides a promising in vitro platform for simulating the pathological microenvironment of OA. This approach can be employed to investigate disease mechanisms, carry out high-throughput drug screening and facilitate personalised therapies. This review summarises joint structure, OA pathogenesis and pathological manifestations, thereby establishing the disease context for the application of organoid technology. It then examines the components of the arthrosis organoid system, specifically addressing cartilage, subchondral bone, synovium, skeletal muscle and ligament organoids. Furthermore, it details various strategies for constructing OA organoids, including considerations of cell selection, pathological classification and fabrication techniques. Notably, this review introduces the concept of intelligent manufacturing of OA organoids by incorporating emerging engineering technologies such as artificial intelligence (AI) into the organoid fabrication process, thereby forming an innovative software and hardware cluster. Lastly, this review discusses the challenges currently facing intelligent OA organoid manufacturing and highlights future directions for this rapidly evolving field. By offering a comprehensive overview of state-of-the-art methodologies and challenges, this review anticipates that intelligent, automated fabrication of OA organoids will expedite fundamental research, drug discovery and personalised translational applications in the orthopaedic field.

Keywords: arthrosis; artificial intelligence; cartilage; in vitro modelling; intelligent manufacturing; osteoarthritis organoids.

FIGURE 1

Overall schematic of intelligent manufacturing in osteoarthritis organoids. Broad overview of the article's structure, outlining the progression from fundamental joint anatomy and OA pathogenesis to organoid construction and, ultimately, to intelligent manufacturing and future prospects. Created with BioRender.com.

FIGURE 2

Comparative depiction of healthy joint anatomy and osteoarthritis pathology. Comparing healthy joints and OA joints, highlighting key pathological changes such as cartilage degeneration, synovial inflammation and bone remodelling. Created with BioRender.com.

FIGURE 3

Subtypes of joint organoids and their application scenarios. Presenting subtypes of organoids, including cartilage, synovium, ligament and bone, and their applications in basic research and disease modelling. Created with BioRender.com.

FIGURE 4

Construction strategies and key technologies for osteoarthritis organoids. Illustrating different seed cell sources, matrix materials, pathological subtypes and core methods such as 3D printing, microfluidics and spheroid self‐assembly. Created with BioRender.com.

FIGURE 5

Workflow for the intelligent manufacturing of osteoarthritis organoids. Focusing on an automated culture system, real‐time sensor feedback, image recognition and big‐data analytics, this figure illustrates the ‘human‐free factory’ concept and how it enables a streamlined, intelligent organoid fabrication process. Created with BioRender.com.

FIGURE 6

Challenges and future outlook in osteoarthritis organoid research. Summarising current obstacles—including issues related to cell sourcing, dynamic culture, material selection and data processing—this figure also highlights potential avenues for high‐throughput drug screening, interdisciplinary integration and personalised therapy. Created with BioRender.com.