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Updated: Nov 6, 2025

Ceramic Omnidirectional Bioprinting in Cell-Laden Suspensions for the Generation of Bone Analogs
Published on: August 8, 2022
Three-Dimensional Cell Printed Lock-Key Structure for Oral Soft and Hard Tissue Regeneration
Shihan Zhang1,2, Qing Li1,2,3, Peng Liu1,2
1Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing, China.
This study explores a new way to help regenerate both soft and hard tissues in the mouth after tooth extraction. Using 3D cell printing, the researchers created a lock-key structure made of two different bioinks. One bioink contained cells for soft tissue growth, while the other included cells for bone formation. The bioink with nano-hydroxyapatite showed better mechanical properties and slower degradation. When implanted in mice, the printed structure integrated well and supported tissue healing. The study suggests that this approach could lead to customized solutions for preserving alveolar ridge volume after tooth loss.
Area of Science:
- Tissue engineering for oral regeneration
- 3D bioprinting in biomedical applications
- Stem cell therapy in dentistry
Background:
Alveolar ridge resorption after tooth extraction remains a significant clinical challenge. The loss of bone and soft tissue volume limits implant rehabilitation options. Prior research has shown that alveolar ridge preservation is critical for successful dental restoration. However, current methods lack the ability to simultaneously regenerate both soft and hard tissues. Three-dimensional (3D) cell printing has emerged as a promising technique due to its spatial control and personalization capabilities. This gap motivated researchers to explore a combined soft-hard tissue construct. No prior work had resolved the integration of both tissue types in a single construct. The need for a biocompatible and structurally stable material remains unmet. This study addresses the challenge of developing a functional construct for alveolar ridge preservation. The potential of 3D cell printing to deliver a customized solution is now being explored.
Purpose Of The Study:
The aim of this study was to develop a 3D cell printed soft-hard construct for alveolar ridge preservation. Alveolar ridge resorption after tooth extraction limits implant options, so a solution that supports both bone and soft tissue is needed. The researchers focused on creating a lock-key structure using two different bioinks. One bioink contained gingival fibroblasts for soft tissue regeneration, while the other included mesenchymal stem cells for bone formation. The motivation was to address the lack of integrated tissue regeneration strategies. The study aimed to test the biocompatibility and structural stability of the construct. The goal was to determine whether the printed structure could support tissue healing in vivo. The researchers proposed that this approach could provide a novel solution for alveolar ridge preservation.
Main Methods:
The study used 3D cell printing to fabricate a soft-hard construct with a lock-key design. Two bioinks were prepared: one with alginate/gelatin and gingival fibroblasts, and another with alginate/gelatin/nano-hydroxyapatite and mesenchymal stem cells. The physicochemical properties of the bioinks were analyzed using X-ray diffraction and mechanical testing. Scanning electron microscopy was used to assess cell attachment and morphology. Cell viability was measured using MTT assays at day 7 post-printing. Gene expression levels of ALP, RUNX-2, and OCN were analyzed via polymerase chain reaction. The constructs were implanted into the dorsum of nude mice for 8 weeks. Histological and structural assessments were conducted to evaluate integration and healing outcomes.
Main Results:
The addition of nano-hydroxyapatite to the bioink preserved its crystalline phase and increased viscosity. The compressive modulus of the AGH bioink was significantly higher than that of AG (p < 0.01). The AGH bioink also showed a slower degradation rate (p < 0.01). SEM images revealed that cells stretched and adhered well on the printed structure. At day 7, GF viability in AG was 94.80% ± 1.14%, and BMSC viability in AGH was 86.59% ± 0.75%. PCR results indicated higher expression of ALP, RUNX-2, and OCN in AGH compared to AG. After 8 weeks of implantation, the cellular construct showed better integration and healing than the acellular version. These findings suggest that the AGH bioink supports bone-related gene expression and tissue regeneration.
Conclusions:
The 3D cell printed soft-hard construct demonstrated favorable biocompatibility and structural integration. The lock-key design allowed for the simultaneous regeneration of soft and hard tissues. The addition of nano-hydroxyapatite improved the mechanical and degradation properties of the bioink. The study found that the AGH bioink supported higher expression of bone-related genes. The printed construct showed better healing outcomes in vivo compared to the acellular version. These findings suggest that the construct has potential for alveolar ridge preservation. The authors propose that this approach could lead to customized plugs for post-extraction healing. The results indicate that 3D cell printing can deliver a functional solution for tissue regeneration.
Frequently Asked Questions
The printed construct showed better integration and healing of subcutaneous tissue in mice compared to an acellular version.
Nano-hydroxyapatite increases viscosity, compressive modulus, and slows degradation of the bioink (<i>p</i> < 0.01).
The lock-key design allows for precise spatial distribution of soft and hard tissue components.
Higher expression of these genes in AGH bioink suggests enhanced osteogenic differentiation of mesenchymal stem cells.
Gingival fibroblasts in AG had 94.80% ± 1.14% viability, and BMSCs in AGH had 86.59% ± 0.75% viability.
The authors propose that the 3D cell printed construct could serve as a customized plug for alveolar ridge preservation.

