A hierarchical bilayer architecture for complex tissue regeneration

Abstract

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro , whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro . After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

Direct preparation of solid carbon dots by pyrolysis of collagen waste and their applications in fluorescent sensing and imaging

“…Solid CDs were obtained from collagen waste by freeze-drying and calcination. So far, our research group has participated in a series of studies-based collagen scaffold and their application in bone and tissue regeneration ( Liu et al, 2016a ; Liu, et al, 2016b ; Liu et al, 2019 ; Wang et al, 2021 ; Yu et al, 2022 ). For example, we used molecular tropocollagen and the assembled collagen scaffold as a carbon source to prepare fluorescent CDs by hydrothermal treatment ( Qiao et al, 2018 ).…”

Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review

“…Several approaches have been used and tested to regenerate teeth [ 67 ]; these approaches have focused on targeted regeneration of individual tooth components such as dental pulp and dentin [for reviews see 68 – 70 ; for functional studies see 70 – 73 ], cementum [for reviews see 74 , 75 ; for functional studies see 76 – 78 ], periodontium [for reviews see 79 , 80 ; for functional studies see 81 – 83 ], and enamel [for reviews see 84 ; for functional studies see 85 – 88 ]. However, combining these strategies does not guarantee the successful regeneration of a viable tooth.…”

Stem cell homing in periodontal tissue regeneration

“…Additionally, a variety of factor-loaded scaffolds for periodontal regeneration have been fabricated. Yu et al (2022) constructed a biphasic scaffold combining intrafibrillarly mineralized collagen (IMC) and concentrated growth factor (CGF) to synergist regeneration of periodontal tissues. In animal experiments, PDLSCs, BMSCs, and induced pluripotent stem cells showed the potential to stimulate the formation of new periodontal tissues ( Ji et al, 2015 ).…”

“…FIGURE 3Potential mechanisms of periodontal hard/soft tissue regeneration by the hierarchical CGF/IMC bilayer architecture. Reprinted from ref(Yu et al (2022)). …”