Structural Design of 3D-Printed Bioceramic Scaffolds

In the field of Bone Tissue Engineering (BTE), achieving a balance between mechanical support and biological regeneration has long been a central challenge for both researchers and clinicians. In recent years, with the rapid convergence of 3D printing and biomanufacturing technologies, bioceramic scaffolds have ushered in a true technological revolution in the area of bone repair.

Natural bone tissue possesses an extraordinarily complex hierarchical architecture, characterized not only by diverse macroscopic morphologies but also by multiscale porosity and mechanical gradients at the microscopic level. Such a structure enables bones to withstand physiological loads while providing an optimal environment for cell migration and angiogenesis. However, reconstructing this intricate system artificially remains a formidable scientific and engineering challenge.

Against this backdrop, personalized structural design has emerged as a critical breakthrough in scaffold fabrication. Leveraging 3D printing technology, researchers can reconstruct the precise morphology of bone defects based on a patient’s medical imaging data (such as CT or MRI scans). Through computer-aided design (CAD) and biomimetic algorithms, it becomes possible to achieve dual customization of the scaffold—both in its macroscopic geometry and microscopic pore architecture.

Such personalized design not only ensures anatomical precision but also significantly enhances biological performance. It facilitates osteoblast adhesion and osteogenic differentiation, improves vascularization, and modulates the immune response, thereby creating a microenvironment conducive to bone regeneration and healing.
 

1. Scaffold Morphology: From Laboratory Fabrication to Clinical “Customization”

Bone defects commonly occur in regions such as the skull, mandible, femur, spine, and alveolar bone, each presenting distinct requirements for the mechanical strength, degradation rate, and geometric configuration of scaffolds. Traditional repair methods typically rely on prefabricated implants, which often fail to meet the complex anatomical and functional needs of individual patients. The advent of 3D printing technology, however, has made patient-specific scaffold fabrication a practical reality.

For instance, in the customized bioceramic scaffold repair of mandibular defects, researchers reconstructed an accurate 3D model of the bone defect from CT scans, and subsequently fabricated a Ca–Si–Mg-based scaffold that precisely matched the defect morphology. When tested in animal models, the scaffold demonstrated effective bone regeneration, fully validating the digital workflow from design to printing to implantation. This approach provides a promising paradigm for translating personalized bone repair from the laboratory to clinical practice.

Meanwhile, composite scaffolds have also been advancing rapidly. For example, Jung et al. fabricated a PEEK/TiO₂/HA composite scaffold using material extrusion technology for the repair of rabbit femoral defects. This scaffold exhibited not only enhanced mechanical durability but also excellent osteointegration performance, offering valuable insights for the development of next-generation, clinically applicable orthopedic implants.

A) Workflow of customized bioceramic scaffolds for mandibular repair and representative optical images of scaffold implantation. B) 3D-printed PEEK/TiO₂/HA composite scaffolds used in orthopedic implantation experiments in rabbit femurs. C) Schematic illustration of femoral scaffold implantation. D) Biomimetic mineralized bone repair material model designed based on patient-specific alveolar bone defect data. E) Ex vivo CaP bone scaffolds fabricated using DLP technology, including human proximal phalanges and Beagle caudal vertebrae samples. F) Schematic of implantation process for 3D-printed PLA/nHA/Li composite scaffolds in rabbit femurs. G) Shape design of BCP scaffolds and their fit with intramedullary nails, applied to 3.0 cm critical-sized femoral defects in goats. H) i) Designed biomimetic structural scaffolds for femoral and cranial repair; ii) Full-scale, anatomically accurate 3D-printed human mandible model compared with the actual mandible; iii) Digital reconstruction of an adult femur, showing longitudinal and cross-sectional morphology; iv) Miniaturized 3D-printed models of human skull, mandible, and upper thoracic vertebrae, achieving seamless integration at interfaces; v) Schematic illustration of scaffold implantation in the femur.

2. Structural Optimization: From TPMS to Biomimetic Mineralization

Although hydroxyapatite (HA) scaffolds have garnered widespread attention due to their excellent biocompatibility and Ca/P ratio closely resembling natural bone, their brittleness and low mechanical strength have limited their practical applications. To overcome these limitations, researchers have introduced the concept of triply periodic minimal surface (TPMS) structures.

TPMS scaffolds feature smooth internal surfaces, interconnected porosity, and geometrically tunable parameters, enabling a significant improvement in bulk modulus and compressive strength without compromising overall porosity. Using SLA printing, the Shi Xuetao group fabricated TPMS-HA scaffolds that achieved enhanced mechanical matching and osteogenic performance, offering a new direction for high-performance biomimetic bone repair structures.

In addition, the Chen zhaoji group employed a “multidimensional biomimetic cascade strategy” to mimic the hierarchical biomineralization of bone tissue, designing a bone repair system capable of simultaneously controlling spatial, temporal, and functional dimensions. By leveraging layered freeze-casting techniques, these scaffolds promoted efficient osteogenesis and vascularization, providing a feasible solution for repairing large-scale bone defects.

3. Modular Approaches: Making Bone Repair “Smarter”

In clinical practice, large-scale or irregular bone defects are often associated with long healing cycles, complex surgeries, and high costs. To address these challenges, researchers have begun exploring the concept of modular scaffolds. For example, Wang et al. employed parametric modeling to construct a digital femur model and personalized fixation plates, providing a digital template for repairing complex fractures. Building on this, the Bartolo team proposed a computational-geometry-based modular biodegradable scaffold system, where algorithms automatically generate 3D printing paths, enabling rapid and flexible scaffold assembly and repair.

In recent years, with the advent of robotic in situ printing and machine-vision assembly systems, the modular concept has gained more practical applications. The Wu Chengtie group combined photocuring 3D printing with modular design to fabricate assembleable and detachable bioceramic scaffold modules. These modules not only allow flexible structural adjustment but also support multi-material co-printing based on different slurry systems. This approach significantly reduces the cost and time associated with repairing complex bone defects, offering a clinically feasible solution that balances efficiency and personalization.

Additionally, researchers have developed a “block-style modular scaffold system” using DLP technology, which leverages machine vision to rapidly match the patient-specific defect morphology, enabling intelligent assembly and precise fitting. Such designs effectively harmonize personalized fabrication with standardized production, laying the foundation for next-generation “smart bone repair” strategies.

A) Simulation of 32-C2 femoral fractures and construction of patient-specific fracture plates: i) 32-C2 fracture simulation; ii) femoral model reconstruction; iii) fracture repair verification; iv) crack rate contour mapping; v) contour parameterization; vi) solid parameterization.B) Customized modular scaffolds for critical-sized bone defects. C) Schematic of the method for directly generating customized large-area bone defect scaffold modules from 2D medical images. D) Structural schematics, photographs, and 3D reconstruction models of 3D-printed assembleable/detachable modular bioceramic scaffolds: i) modular scaffolds assembled from circular modules; ii) modular scaffolds assembled from square modules; iii) modular scaffolds with a Tower of Hanoi configuration; iv) modular scaffolds assembled from five layers of 3D-printed circular modules; v) 3D-printed square modules that can be assembled into scaffolds of varying sizes; vi) Tower of Hanoi modular scaffolds assembled from circular modules of different diameters; vii) 3D-printed scaffold modules assembled into various customized structures (e.g.,“SIC”); viii) Micro-CT 3D reconstruction of circular modular scaffolds. E) Structural schematics of modular bioceramic scaffolds: i) types of bone unit interfaces, including trapezoidal and T-shaped interfaces; ii) 2D schematic of bone unit components; iii) 3D schematic of bone unit components; iv) innovative modular scaffold assembly system, enabling rapid, intelligent assembly and precise matching of patient-specific complex bone defect anatomies.

4. Pore Architecture: Integrating Biomimetic Inspiration with Structural Innovation

Pore design is a critical factor influencing the performance of bone scaffolds. An ideal scaffold must not only provide sufficient mechanical strength but also feature interconnected porosity to support cell infiltration and vascularization.

Researchers have drawn inspiration from nature’s ingenuity. For example, the luffa-inspired structure: the Chen Qinghua team used luffa as a template to fabricate highly porous HA scaffolds with interconnected pores, significantly enhancing bone tissue repair. The lotus seedpod-inspired structure: the Wang Peng team employed DLP technology to design a “seed–petal” scaffold, incorporating deferoxamine (DFO)-loaded liposomal hydrogel microspheres to achieve dual regulation of angiogenesis and osteogenesis.

Additionally, the nacre-inspired structure: Academician Yu Shuhong’s group utilized a biomimetic co-mineralization approach on chitin templates, enabling nanoscale particle co-mineralization that markedly improved the toughness and dynamic mechanical properties of ceramic blocks. These biomimetic designs not only enhance the mechanical and biological performance of scaffolds but also highlight the immense potential of biomimetic strategies at the intersection of materials science and regenerative medicine.

The schematic of pore design in bone scaffolds illustrates various design concepts:A) 3D-printed bioceramic scaffold inspired by the unique biological structure of a lotus seedpod; B) Nacre-structured ceramics, including both photographs of the actual material and schematic of synthesis; C) TPMS models of six 3D-printed hydroxyapatite (HA) scaffolds (1 cm × 1 cm × 1 cm); D) 3D-printed scaffolds with cylindrical, helical, and diamond-shaped pore geometries; E) Cylindrical and spherical samples with pore units that increase in diameter layer by layer, presenting a three-level gradient pore distribution; F) Design models of polyhedral bioceramic scaffolds and intersecting scaffolds.

5. TPMS and Gradient Pore Design: Toward Precision Control

Triply Periodic Minimal Surface (TPMS) structures have become a focal point in bone scaffold research due to their continuous, smooth surfaces with zero mean curvature. These structures not only provide highly interconnected porosity but also allow precise control of pore size and wall thickness through mathematical functions.
 

Studies have shown that TPMS scaffolds can significantly enhance compressive strength while maintaining porosity. Additionally, the release of Mg²⁺ ions is more uniform, promoting osteoblast proliferation and differentiation. Researchers have also explored gradient pore designs, introducing pore size gradients across different regions to mimic the functional transition from cortical to cancellous bone, thereby optimizing both cellular behavior and mechanical response.
 

For example, Juan Ye et al. used DLP technology to fabricate gradient-distributed hard silicate (Ca₂ZnSi₂O₇) scaffolds with continuously varying pore sizes from 500 to 800 µm, demonstrating excellent osteogenic performance in vivo.

This combination of functional gradients and biomimetic structural design is emerging as a key trend in the future of bioceramic 3D printing.

5. TPMS and Gradient Pore Design: Toward Precision Control

3D printing is propelling personalized bone scaffolds from the laboratory to the clinic. Through systematic optimization of structure, materials, mechanics, and biological performance, the functional boundaries of bioceramic scaffolds are continually being expanded.
 

Nevertheless, challenges remain—limited material toughness, difficulty in controlling degradation rates, high costs, equipment constraints, and long clinical validation cycles—requiring ongoing multidisciplinary collaboration across materials science, mechanical engineering, biology, and medicine.
 

It is foreseeable that, with advances in artificial intelligence-driven design, 4D printing, and smart biomaterials, future bioceramic bone scaffolds will transcend the role of simple tissue substitutes, evolving into truly integrated regenerative systems.
 

At that point, 3D printing will no longer be merely a tool for fabricating bones, but a key technology for reshaping the architecture of life itself.