title: Advancing synthetic bone grafts
title: leveraging microRNAs and 3D-printing to enhance bone regeneration
titleType: Subtitle
Creators: name: Remy, Matthew Thomas
Publisher: name: University of Iowa
Year: 2025
Subjects: 3D printing
biomaterials
bone regeneration
microRNAs
synthetic bone grafts
public abstract
Tissue Engineering

description: Large bone defects are clinically challenging to treat and often necessitate bone grafting. Natural grafting options include autografts and allografts; however, these replacement tissues are limited in supply and difficult to match to the geometric irregularities of complex bone defects. With over two million bone grafting procedures completed annually, the high demand for replacement tissues cannot be satisfied by natural grafts alone. The development of tissue-engineered (TE) synthetic bone grafts has become essential to overcome the limitations of natural grafts; yet deficient scaffold fabrication methods and inefficient osteoinductive agents have prevented the clinical translation of traditional TE constructs. Therefore, innovative strategies that combine advanced scaffold fabrication methods, like 3D printing, with effective biomolecules, such as osteoinductive microRNAs, are key to developing advanced synthetic bone grafts that overcome natural grafting limitations to improve clinical bone regeneration.MicroRNAs (miRs) are essential regulators of gene expression for a variety of biological processes, including osteogenesis. miR-200c has previously demonstrated osteoinductive capabilities by increasing osteogenic differentiation and bone formation; however, tissue engineering strategies aimed at incorporating miR-200c into synthetic bone grafts to enhance bone regeneration have yet to be evaluated. For the treatment of large bone defects, synthetic grafts incorporating osteoinductive miR-200c may provide a mechanism to enhance regenerative signaling and maximize bone regeneration. This work investigates the design of synthetic bone grafts incorporating miR-200c for bone regeneration and evaluates how different biomaterial combinations, scaffold fabrication methods, and delivery systems influence bone regeneration.
description: The first objective of this work examines the capacity for pDNA encoding miR-200c to enhance bone regeneration via incorporation into 3D-printed synthetic bone grafts. Our results
description: viii
description: demonstrate that miR-200c incorporation significantly enhances bone regeneration in critical-sized bone defects, therefore indicating that miR-200c can improve bone formation using 3D-printed synthetic bone grafts. Our next objective was to characterize the release of pDNA encoding miR-200c from natural polymer coatings on 3D-printed synthetic scaffolds. For this objective, we aimed to develop a pDNA delivery system to sustain miR-200c release and prolong regenerative signaling to maximize bone regeneration. Using basic gelatin coatings on 3D-printed synthetic grafts, we found that we could extend the release of pDNA encoding miR-200c to enhance bone regeneration in critical-sized bone defects. Finally, our last objective evaluated the influence of calcium carbonate-based nanoparticles on improving pDNA delivery to increase miR-200c transfection efficiency and enhance bone regeneration. This objective also investigated the regenerative potential of miR-200c using a clinically applicable, alveolar bone defect model relevant to restoring bone defects from oral squamous cell carcinoma treatment. Our results indicate that co-precipitation of calcium carbonate nanoparticles with pDNA encoding miR-200c effectively improves cell transfection and enhances bone regeneration in alveolar bone defects.
description: This work leverages the combined use of different biomaterials, innovative additive manufacturing technologies, and drug incorporation methods to develop miR-incorporated synthetic bone grafts capable of enhancing bone regeneration. Furthermore, this work is the first to critically evaluate the release of pDNA encoding miR-200c from synthetic bone grafts and the influence of miR-200c as an osteoinductive agent for bone tissue engineering. The culmination of this work significantly advances the development of synthetic bone grafts with improved regenerative properties and supplies the field with novel, miR-based strategies to enhance bone regeneration for the clinical treatment of challenging, patient-specific, large bone defects.