Functionalization of Ceramic Scaffolds with Exosomes from Bone Marrow Mesenchymal Stromal Cells for Bone Tissue Engineering.

The functionalization of bone substitutes with exosomes appears to be a promising technique to enhance bone tissue formation. This study investigates the potential of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) to improve bone healing and bone augmentation when incorporated into wide open-porous 3D-printed ceramic Gyroid scaffolds. We demonstrated the multipotent characteristics of BMSCs and characterized the extracted exosomes using nanoparticle tracking analysis and proteomic profiling. Through cell culture experimentation, we demonstrated that BMSC-derived exosomes possess the ability to attract cells and significantly facilitate their differentiation into the osteogenic lineage. Furthermore, we observed that scaffold architecture influences exosome release kinetics, with Gyroid scaffolds exhibiting slower release rates compared to Lattice scaffolds. Nevertheless, in vivo implantation did not show increased bone ingrowth in scaffolds loaded with exosomes, suggesting that the scaffold microarchitecture and material were already optimized for osteoconduction and bone augmentation. These findings highlight the lack of understanding about the optimal delivery of exosomes for osteoconduction and bone augmentation by advanced ceramic scaffolds.

TPMS Microarchitectures for Vertical Bone Augmentation and Osteoconduction: An In Vivo Study.

Triply periodic minimal surface microarchitectures (TPMS) were developed by mathematicians and evolved in all kingdoms of living organisms. Renowned for their lightweight yet robust attributes, TPMS structures find application in diverse fields, such as the construction of satellites, aircrafts, and electric vehicles. Moreover, these microarchitectures, despite their intricate geometric patterns, demonstrate potential for application as bone substitutes, despite the inherent gothic style of natural bone microarchitecture. Here, we produced three TPMS microarchitectures, D-diamond, G-gyroid, and P-primitive, by 3D printing from hydroxyapatite. We explored their mechanical characterization and, further, implanted them to study their bone augmentation and osteoconduction potential. In terms of strength, the D-diamond and G-gyroid performed significantly better than the P-primitive. In a calvarial defect model and a calvarial bone augmentation model, where osteoconduction is determined as the extent of bony bridging of the defect and bone augmentation as the maximal vertical bone ingrowth, the G-gyroid performed significantly better than the P-primitive. No significant difference in performance was observed between the G-gyroid and D-diamond. Since, in real life, the treatment of bone deficiencies in patients comprises elements of defect bridging and bone augmentation, ceramic scaffolds with D-diamond and G-gyroid microarchitectures appear as the best choice for a TPMS-based scaffold in bone tissue engineering.

Optimizing Filament-Based TCP Scaffold Design for Osteoconduction and Bone Augmentation: Insights from In Vivo Rabbit Models.

Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact that the majority of 3D-printers generate filament-based structures. Here, we investigated the influence of filament characteristics on bone regeneration outcomes using a lithography-based additive manufacturing approach. Three distinct filament-based scaffolds (Fil050, Fil083, and Fil125) identical in macroporosity and transparency, crafted from tri-calcium phosphate (TCP) with varying filament thicknesses and distance, were evaluated in a rabbit model of bone augmentation and non-critical calvarial defect. Additionally, two scaffold types differing in filament directionality (Fil and FilG) were compared to elucidate optimal design parameters. Distance of bone ingrowth and percentage of regenerated area within scaffolds were measured by histomorphometric analysis. Our findings reveal filaments of 0.50 mm as the most effective filament-based scaffold, demonstrating superior bone ingrowth and bony regenerated area compared to larger size filament (i.e., 0.83 mm and 1.25 mm scaffolds). Optimized directionality of filaments can overcome the reduced performance of larger filaments. This study advances our understanding of microarchitecture's role in bone tissue engineering and holds significant implications for clinical practice, paving the way for the development of highly tailored, patient-specific bone substitutes with enhanced efficacy.

Enhanced bone regeneration in rat calvarial defects through BMP2 release from engineered poly(ethylene glycol) hydrogels.

The clinical standard therapy for large bone defects, typically addressed through autograft or allograft donor tissue, faces significant limitations. Tissue engineering offers a promising alternative strategy for the regeneration of substantial bone lesions. In this study, we harnessed poly(ethylene glycol) (PEG)-based hydrogels, optimizing critical parameters including stiffness, incorporation of arginine-glycine-aspartic acid (RGD) cell adhesion motifs, degradability, and the release of BMP2 to promote bone formation. In vitro we demonstrated that human bone marrow derived stromal cell (hBMSC) proliferation and spreading strongly correlates with hydrogel stiffness and adhesion to RGD peptide motifs. Moreover, the incorporation of the osteogenic growth factor BMP2 into the hydrogels enabled sustained release, effectively inducing bone regeneration in encapsulated progenitor cells. When used in vivo to treat calvarial defects in rats, we showed that hydrogels of low and intermediate stiffness optimally facilitated cell migration, proliferation, and differentiation promoting the efficient repair of bone defects. Our comprehensive in vitro and in vivo findings collectively suggest that the developed hydrogels hold significant promise for clinical translation for bone repair and regeneration by delivering sustained and controlled stimuli from active signaling molecules.

Patient-specific beta-tricalcium phosphate scaffold for customized alveolar ridge augmentation: a case report : Case Report: patient-specific ß-TCP scaffold for alveolar ridge CBR.

BACKGROUND: Beta-tricalcium phosphate (ß-TCP) is a biocompatible ceramic material widely used in the field of oral regeneration. Due to its excellent biological and mechanical properties, it is increasingly utilized for alveolar ridge augmentation or guided bone regeneration (GBR). With recent advances in computer-aided design and manufacturing (CAD/CAM), ß-TCP can now be used in the form of digitally designed patient-specific scaffolds for customized bone regeneration (CBR) of advanced defects in a two-stage implant therapy concept. In this case report following the CARE case report guidelines, we present a novel application of a patient-specific ß-TCP scaffold in pre-implant mandibular alveolar ridge augmentation. CASE PRESENTATION: A 63-year-old female patient with significant horizontal bone loss in the posterior mandible was treated with a custom ß-TCP scaffold in the context of a two-stage backward-planned implant therapy. Cone-beam computed tomography nine months after augmentation showed successful integration of the scaffold into the surrounding bone, allowing implant placement. Follow-up until two years after initial surgery showed excellent oral and peri-implant health. CONCLUSIONS: This case highlights the potential of patient-specific ß-TCP scaffolds for alveolar ridge augmentation and their advantage over traditional techniques, including avoidance of xeno-, allo-, and autografts. The results provide encouraging evidence for their use in clinical practice. Patient-specific ß-TCP scaffolds may be a promising alternative for clinicians seeking to provide their patients with safe, predictable, and effective alveolar ridge augmentation results in customized bone regeneration procedures.

3D Printing of Dental Prostheses: Current and Emerging Applications.

Revolutionary fabrication technologies such as three-dimensional (3D) printing to develop dental structures are expected to replace traditional methods due to their ability to establish constructs with the required mechanical properties and detailed structures. Three-dimensional printing, as an additive manufacturing approach, has the potential to rapidly fabricate complex dental prostheses by employing a bottom-up strategy in a layer-by-layer fashion. This new technology allows dentists to extend their degree of freedom in selecting, creating, and performing the required treatments. Three-dimensional printing has been narrowly employed in the fabrication of various kinds of prostheses and implants. There is still an on-demand production procedure that offers a reasonable method with superior efficiency to engineer multifaceted dental constructs. This review article aims to cover the most recent applications of 3D printing techniques in the manufacturing of dental prosthetics. More specifically, after describing various 3D printing techniques and their advantages/disadvantages, the applications of 3D printing in dental prostheses are elaborated in various examples in the literature. Different 3D printing techniques have the capability to use different materials, including thermoplastic polymers, ceramics, and metals with distinctive suitability for dental applications, which are discussed in this article. The relevant limitations and challenges that currently limit the efficacy of 3D printing in this field are also reviewed. This review article has employed five major scientific databases, including Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus, with appropriate keywords to find the most relevant literature in the subject of dental prostheses 3D printing.