Biomimetic Materials for Bone Regeneration - PhDData

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Biomimetic Materials for Bone Regeneration

The thesis was published by Li, Shuyi, in September 2022, VU University Amsterdam.


The repair of large bone defects remains challenging due to the respective limitations of the clinically available bone grafts. Therefore, continuous efforts have been made to develop new bone and periosteum substitutes to enhance bone regeneration. HUCMSCs are promising stem cells for bone tissue engineering. However, a series of in-vitro studies have shown that the osteogenic efficacy of hUCMSCs is relatively lower than that of BMSCs. Therefore, in Chapter 2, we adopted a biomimetic strategy of co-culturing osteogenically- and angiogenically-committed hUCMSCs in various mixing ratios and culture media to promote the osteogenic efficacy of hUCMSCs. Compared with mono-cultured osteogenically-committed hUCMSCs in OM, a 3:1 ratio of osteogenically- and angiogenically-committed cells co-cultured in a 3:1 ratio of osteogenic medium and endothelial cell induction medium bore dramatically higher osteogenic properties, thus providing a novel strategy to fabricate hUCMSC-based biomimetic BTE constructs with enhanced osteogenic efficacy. It is established that ECM hydrogels bear a tissue-specific induction property. Therefore, in Chapter 3, decellularized periosteum-derived hydrogels (dPH) were fabricated and compared with the non-periosteum/bone-specific ECM hydrogel, Matrigel. Our study showed dPH exhibited a prominent effect on promoting the initial cellular spreading, migration, and proliferation. Moreover, the dPH group was associated with the enhanced osteogenesis-related genes expression and mineralized matrix formation of hUCMSCs than that of Matrigel. Our study indicated a promising application potential of biomimetic hUCMSCs/dPH constructs to repair bone defects. BioCaP coating has long been used to confer bone constructs an osteoconductive surface and enhanced scaffold-cell interactions. However, its biomedical application is limited by the low coating yield efficiency and protein-incorporation rate of the current coating procedure using 1× supersaturated CaP solution (SCPS). Therefore, in Chapter 4, we developed a highly concentrated 4.5× SCPS solution to harvest BioCaP coating. The thereby produced coating bore several advantages over the original coating, such as a higher coating yield efficiency and protein-incorporating rate. The new coating was identified as DCPD/apatite crystalline and showed a strong acid-resistant property. These properties conferred the new coating a promising potential in the functionalization of titanium implants for biomedical applications. Polydopamine (pDA) coating is a simple and effective method to modify scaffolds, thus covalently immobilizing growth factors and increasing surface bioactivity. Whether 3D printed TCP scaffolds functionalized by pDA-immobilized BMP2 were superior in prefabricating biomimetic bone grafts than the scaffolds functionalized by the superficially adsorbed one in latissimus dorsi muscle remained to be studied. Therefore, in Chapter 5, pDA-coated TCP (TCP/pDA) scaffolds were fabricated and characterized. Our study demonstrated that pDA coating was an efficacious method to improve the loading efficacy of BMP2 on the scaffolds, which also ensured a slow release profile of the loaded BMP2. Besides, pDA-immobilized BMP2 significantly promoted the osteogenic differentiation of C2C12 and the in-vivo bone formation. Our data suggested that the 3D printed TCP scaffolds functionalized with pDA-immobilized BMP2 were promising to prefabricate biomimetic bone grafts for repairing large bone defects. The development of tissue-engineered periosteum (TEP) is a promising strategy to accelerate the repair of bone defects. However, the previously developed TEPs lack periosteum-specific niches to regulate cellular activities and are hard to realize genuine biomimetic periosteum in composition. Therefore, in Chapter 6, we adopted the co-axial electrospinning technique to fabricate a novel biomimetic TEP with PCL-core/dECM-shell-structured microfibers. The novel PEC resembled the mechanical strength of the PCL membrane and bore dECM-like hydrophilicity and bioactivity to promote cell spreading, proliferation, and osteogenic activities. Moreover, PEC bore a comparable healing efficacy in repairing bone defects to the pure ECM, which was significantly higher than that in the pure PCL membrane. These findings indicated a promising application potential of the novel PEC-TEP in repairing bone defects.

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