ArticleScience translational medicine2019
Recapitulating bone development through engineered mesenchymal condensations and mechanical cues for tissue regeneration.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
86 citing papers in PubMed.
- Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio-Interactive Materials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Hydrogel Implementing Drug Delivery in Cranial Bone Tissue Engineering.Journal of functional biomaterials · 2026Review
- Gli1⁺ cell aggregates promote type H vessel formation and orchestrate bone defect regeneration.Stem cell research & therapy · 2026Article
- Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy.Advanced healthcare materials · 2026Review
- Development-based In Vivo Bioreactor Strategy for Challenging Senescent Bone Reconstruction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sulfated polysaccharide reprograms arterialized angiogenesis of endochondral ossification to rescue defective osteonecrosis therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Start, Stop, Rewind, Repeat-Cyclic Exposure of Adipose Stromal Cells-derived Cartilage Organoids to Chondrogenic and Proliferative Cues to Achieve Scaled-up and Customizable Bone Formation by Endochondral Ossification.Advanced healthcare materials · 2026Article
- Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Engineering polyphenol-based osteogenic system for bone and cartilage repair: Transplantation, tissue engineering, and organoid.Journal of advanced research · 2026Review
- The utility of 3D nanostructured polyglycolic acid fibers for novel bone regenerative medicine.Journal of dental sciences · 2026Article
- Mechanotransduction Mediated by PDLIM5: The Critical Role of Serpin E2/Integrin β3-Cytoskeleton-Nucleoskeleton Axis in Mechanical Osteogenic Programming.Cell proliferation · 2025Article
- Erythroid precursors regulate local oxygen tension and repair outcomes in the bone marrow niche.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Compression injury regulates astrocyte morphology, metabolic function, and extracellular matrix modification in a 3D hydrogel.bioRxiv : the preprint server for biology · 2025Article
- Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects.Bioactive materials · 2025Article
- Erythroid precursors regulate local oxygen tension and repair outcomes in the bone marrow niche.bioRxiv : the preprint server for biology · 2025Article
- Single-cell transcriptomics identifies PDGFRAInternational journal of oral science · 2025Article
- Divide-and-conquer strategy with engineered ossification center organoids for rapid bone healing through developmental cell recruitment.Nature communications · 2025Article
- Cartilaginous microtissues exhibit extreme resilience under compression with size-dependent mechanical properties.Biomaterials · 2025Article
- 3D-Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia-Induced Exosomes for Dual-Mimetic Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Degradable poly-lactic-co-glycolic acid and non-degradable polymer implants result in similar fracture healing at early timepoints.Clinical biomechanics (Bristol, Avon) · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Large bone defects cannot form a callus and exhibit high complication rates even with the best treatment strategies available. Tissue engineering approaches often use scaffolds designed to match the properties of mature bone. However, natural fracture healing is most efficient when it recapitulates development, forming bone via a cartilage intermediate (endochondral ossification). Because mechanical forces are critical for proper endochondral bone development and fracture repair, we hypothesized that recapitulating developmental mechanical forces would be essential for large bone defect regeneration in rats. Here, we engineered mesenchymal condensations that mimic the cellular organization and lineage progression of the early limb bud in response to local transforming growth factor-β1 presentation from incorporated gelatin microspheres. We then controlled mechanical loading in vivo by dynamically tuning fixator compliance. Mechanical loading enhanced mesenchymal condensation-induced endochondral bone formation in vivo, restoring functional bone properties when load initiation was delayed to week 4 after defect formation. Live cell transplantation produced zonal human cartilage and primary spongiosa mimetic of the native growth plate, whereas condensation devitalization before transplantation abrogated bone formation. Mechanical loading induced regeneration comparable to high-dose bone morphogenetic protein-2 delivery, but without heterotopic bone formation and with order-of-magnitude greater mechanosensitivity. In vitro, mechanical loading promoted chondrogenesis and up-regulated pericellular matrix deposition and angiogenic gene expression. In vivo, mechanical loading regulated cartilage formation and neovascular invasion, dependent on load timing. This study establishes mechanical cues as key regulators of endochondral bone defect regeneration and provides a paradigm for recapitulating developmental programs for tissue engineering.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.