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This review focuses on the repair challenges brought about by the simultaneous damage of subchondral bone and adjacent cartilage tissues in osteochondral defects. It centers on the demand for bone tissue regeneration and systematically reviews the latest research achievements in the preparation techniques of 3D-printed multiphase scaffolds, the selection of biomaterials, and the structural design in this field. It deeply analyzes the bone-related compatibility characteristics and functional advantages of various technologies, materials, and structures, and integrates research progress from multiple fields such as materials science and bioengineering. It constructs a rational design framework for the next-generation osteochondral multiphase scaffolds based on bone tissue regeneration as the core orientation, providing clear theoretical references and direction guidance for subsequent research exploration in this field. This review addresses the regeneration and repair dilemma caused by the heterogeneity of osteochondral tissues, with the tissue engineering system combining mesenchymal stem cells and biomaterial scaffolds as the core. It clarifies the regulatory mechanism of biological physical signals on the fate of stem cells, systematically summarizes the design progress of biomimetic microenvironment scaffolds under the guidance of mechanical biology, and precisely regulates the lineage-specific differentiation of mesenchymal stem cells, providing theoretical support and design references for layered osteochondral regeneration, especially the regeneration of subchondral bone.
01 Research Background
Osteochondral defects are complex tissue injuries that simultaneously affect articular cartilage, calcified cartilage, and subchondral bone tissues. Subchondral bone, as a key component of bone tissue, possesses unique mechanical bearing and biological functions, and forms a hierarchical heterogeneous structure with adjacent cartilage tissues. This natural hierarchical difference and functional differentiation make the integrated repair of osteochondral tissues face technical bottlenecks. Simple traditional repair methods are difficult to meet the different repair requirements of bone and cartilage tissues. Osteochondral tissue engineering, with the research idea of multiphase scaffolds, has become a potential direction to solve this problem. Its core logic is to simulate the heterogeneity of the original osteochondral unit composition and structure through scaffold design, and to specifically meet the repair needs of bone tissue, such as mechanical support and growth microenvironment construction. The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and the gradient composition of minerals. This structural system can achieve stable force transmission and guide the cell phenotype of spatial organization. Currently, the complex multi-scale structure and composition gradient at the tendon-bone interface cannot be precisely reproduced, which has become a key bottleneck hindering the integration regeneration of soft and hard tissues. It is urgently necessary to develop a biomimetic matrix construction scheme that conforms to the natural structure characteristics.
02 Main Content
This review first focuses on the preparation process of osteochondral multiphase scaffolds, comprehensively examines three core additive manufacturing technologies: material extrusion, slot photopolymerization, and powder bed fusion. It details the working principles, material compatibility range, precise manufacturing capabilities of each technology, and their specific application performances in osteochondral scaffold design; then systematically reviews various biomaterials used in osteochondral scaffolds, including polymers, bioceramics, biodegradable metals, and advanced composite materials. It focuses on analyzing the bone-related biomechanical characteristics of single material systems and the synergistic effect of bone repair functions achieved through component combination in composite materials; then deeply explores the design ideas of multiphase scaffolds, comprehensively analyzing the latest progress of two mainstream designs: multi-layer architecture and gradient architecture, and elaborating on their mechanisms of action on the specific mechanical support of bone tissue regions, material transport regulation, and tissue interface integration; finally, it comprehensively reviews the future development directions in this field, including the research and development of new osteogenic biomaterials and the application of intelligent design methods.
03 Research Design This research adopts a systematic review study design, focusing on the repair requirements of bone tissue in bone cartilage regeneration. It employs a scientific research approach of classification and integration, first clarifying the core pain points and research necessity of bone tissue repair in bone cartilage defects, and then, following the logical framework of "preparation technology - biomaterials - structural design - future prospects", conducting layered research and in-depth analysis of the existing research results within the field. The entire process focuses on the mechanical properties and biological functional compatibility of bone tissue. By integrating multi-dimensional research progress, a complete review research system is formed, ensuring the comprehensiveness and targeted nature of the research content.
04 Results
The study identified the differentiated advantages of three mainstream additive manufacturing technologies in the preparation of bone cartilage multiphase scaffolds, as well as their respective application characteristics suitable for bone phase structure manufacturing; it sorted out the bone-related biomechanical performance characteristics of four core biomaterials, confirming that composite materials can integrate the advantages of single materials to achieve the synergistic enhancement of bone repair functions, and are more suitable for the needs of bone tissue regeneration; it verified that multi-layer and gradient scaffolds can achieve precise mechanical support and interface integration optimization for bone tissue regions, effectively matching the structure and functional characteristics of native bone tissue; ultimately, a bone-targeted multiphase scaffold design system integrating technology, materials, and structure progress was formed, providing complete theoretical support for subsequent scaffold research.
05 Extension of Ideas
In the future, research can be targeted at the natural mechanical properties and biological microenvironment of bone tissue, developing new biomaterials that are compatible with mechanical performance and have excellent bone conduction, further optimizing the biocompatibility of materials and bone tissue; combined with artificial intelligence-assisted design, medical image modeling, etc., precisely replicate the hierarchical structure characteristics of bone tissue, achieve personalized and refined design of scaffold bone phase structure; deeply explore the gradient structure design of the bone-cartilage interface of multiphase scaffolds, weaken the performance differences between tissues, and improve the interface fusion effect between bone and adjacent tissues; at the same time, expand multi-scale structural regulation strategies to further optimize the microenvironment required for bone tissue regeneration and enrich the research paths of bone cartilage tissue engineering scaffolds.
