The reconstruction of large bone defects by novel functionalized polymers: an in vitro and in vivo experimental study

1993 ◽  
Vol 12 (13) ◽  
pp. 979-981 ◽  
Author(s):  
E. Dalas ◽  
P. Megas ◽  
M. Tyllianakis ◽  
D. Vynois ◽  
E. Lambiris
Keyword(s):  
Experimental Study ◽  
Bone Defects ◽  
Functionalized Polymers ◽  
Large Bone ◽  
Large Bone Defects

Fabrication of piezoelectric porous BaTiO3 scaffold to repair large segmental bone defect in sheep

2020 ◽  
Vol 35 (4-5) ◽  
pp. 544-552 ◽  
Author(s):  
Wenwen Liu ◽  
Di Yang ◽  
Xinghui Wei ◽  
Shuo Guo ◽  
Ning Wang ◽  
...  
Keyword(s):  
Electric Field ◽  
Bone Defect ◽  
Piezoelectric Effect ◽  
Bone Defects ◽  
Segmental Bone Defect ◽  
Segmental Bone ◽  
Large Bone ◽  
Large Bone Defects

Porous titanium scaffolds can provide sufficient mechanical support and bone growth space for large segmental bone defect repair. However, they fail to restore the physiological environment of bone tissue. Barium titanate (BaTiO3) is considered a smart material that can produce an electric field in response to dynamic force. Low-intensity pulsed ultrasound stimulation (LIPUS), as a kind of micromechanical wave, can not only promote bone repair but also induce BaTiO3 to generate an electric field. In our studies, BaTiO3 was coated on porous Ti6Al4V and LIPUS was externally applied to observe the influence of the piezoelectric effect on the repair of large bone defects in vitro and in vivo. The results show that the piezoelectric effect can effectively promote the osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro as well as bone formation and growth into implants in vivo. This study provides an optional alternative to the conventional porous Ti6Al4V scaffold with enhanced osteogenesis and osseointegration for the repair of large bone defects.

scholarly journals Vascularization of Nanohydroxyapatite/Collagen/Poly(L-lactic acid) Composites by Implanting Intramuscularly In Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Hai Wang ◽  
Xiao Chang ◽  
Guixing Qiu ◽  
Fuzhai Cui ◽  
Xisheng Weng ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Orthopaedic Surgery ◽  
Bone Substitutes ◽  
Bone Defects ◽  
Large Defect ◽  
Natural Bone ◽  
Composition And Structure ◽  
Large Bone ◽  
Large Bone Defects

It still remains a major challenge to repair large bone defects in the orthopaedic surgery. In previous studies, a nanohydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composite, similar to natural bone in both composition and structure, has been prepared. It could repair small sized bone defects, but they were restricted to repair a large defect due to the lack of oxygen and nutrition supply for cell survival without vascularization. The aim of the present study was to investigate whether nHAC/PLA composites could be vascularized in vivo. Composites were implanted intramuscularly in the groins of rabbits for 2, 6, or 10 weeks (n=5×3). After removing, the macroscopic results showed that there were lots of rich blood supply tissues embracing the composites, and the volumes of tissue were increasing as time goes on. In microscopic views, blood vessels and vascular sprouts could be observed, and microvessel density (MVD) of the composites trended to increase over time. It suggested that nHAC/PLA composites could be well vascularized by implanting in vivo. In the future, it would be possible to generate vascular pedicle bone substitutes with nHAC/PLA composites for grafting.

Hydroxyapatite scaffold pore architecture effects in large bone defects in vivo

2013 ◽  
Vol 28 (7) ◽  
pp. 1016-1027 ◽  
Author(s):  
Teja Guda ◽  
John A Walker ◽  
Brian Singleton ◽  
Jesus Hernandez ◽  
Daniel S Oh ◽  
...  
Keyword(s):  
Bone Defects ◽  
Pore Architecture ◽  
Hydroxyapatite Scaffold ◽  
Large Bone ◽  
Large Bone Defects

scholarly journals Recapitulating bone development for tissue regeneration through engineered mesenchymal condensations and mechanical cues

2017 ◽  
Author(s):  
Anna M. McDermott ◽  
Samuel Herberg ◽  
Devon E. Mason ◽  
Hope B. Pearson ◽  
James H. Dawahare ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Formation ◽  
Mechanical Loading ◽  
Endochondral Ossification ◽  
Bone Development ◽  
Bone Defects ◽  
Limb Bud ◽  
Large Bone ◽  
Large Bone Defects

ABSTRACTLarge bone defects cannot heal without intervention and have high complication rates even with the best treatments available. In contrast, bone fractures naturally healing with high success rates by recapitulating the process of bone development through endochondral ossification.1 Endochondral tissue engineering may represent a promising paradigm, but large bone defects are unable to naturally form a callus. We engineered mesenchymal condensations featuring local morphogen presentation (TGF-β1) to mimic the cellular organization and lineage progression of the early limb bud. As mechanical forces are 2,3 critical for proper endochondral ossification during bone morphogenesis2,3 and fracture healing, we hypothesized that mechanical cues would be important for endochondral regeneration.4,5 Here, using fixation plates that modulate ambulatory load transfer through dynamic tuning of axial compliance, we found that in vivo mechanical loading was necessary to restore bone function to large bone defects through endochondral ossification. Endochondral regeneration produced zonal cartilage and primary spongiosa mimetic of the native growth plate. Live human chondrocytes contributed to endochondral regeneration in vivo, while cell devitalization prior to condensation transplantation abrogated bone formation. Mechanical loading induced regeneration comparable to high-dose BMP-2 delivery, but without heterotopic bone formation and with order-of-magnitude greater mechanosensitivity.6–8In vitro, mechanical loading promoted chondrogenesis, and upregulated pericellular collagen 6 deposition and angiogenic gene expression. Consistently, in vivo mechanical loading regulated cartilage formation and neovascular invasion dependent on load timing. Together, this study represents the first demonstration of the effects of mechanical loading on transplanted cell-mediated bone defect regeneration, and provides a new template for recapitulating developmental programs for tissue engineering.

scholarly journals Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration

2020 ◽  
Vol 6 (1) ◽  
pp. eaay1240 ◽  
Author(s):  
Marian H. Hettiaratchi ◽  
Laxminarayanan Krishnan ◽  
Tel Rouse ◽  
Catherine Chou ◽  
Todd C. McDevitt ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Bone Morphogenetic Protein ◽  
Spatial Localization ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Large Bone ◽  
Large Bone Defects

Supraphysiologic doses of bone morphogenetic protein-2 (BMP-2) are used clinically to promote bone formation in fracture nonunions, large bone defects, and spinal fusion. However, abnormal bone formation (i.e., heterotopic ossification) caused by rapid BMP-2 release from conventional collagen sponge scaffolds is a serious complication. We leveraged the strong affinity interactions between heparin microparticles (HMPs) and BMP-2 to improve protein delivery to bone defects. We first developed a computational model to investigate BMP-2–HMP interactions and demonstrated improved in vivo BMP-2 retention using HMPs. We then evaluated BMP-2–loaded HMPs as a treatment strategy for healing critically sized femoral defects in a rat model that displays heterotopic ossification with clinical BMP-2 doses (0.12 mg/kg body weight). HMPs increased BMP-2 retention in vivo, improving spatial localization of bone formation in large bone defects and reducing heterotopic ossification. Thus, HMPs provide a promising opportunity to improve the safety profile of scaffold-based BMP-2 delivery.

Study of the Effect of Mechanical Loading on Cell Cultures in Bone Tissue Engineering

2012 ◽  
Author(s):  
Magali Cruel ◽  
Morad Bensidhoum ◽  
Laure Sudre ◽  
Guillaume Puel ◽  
Virginie Dumas ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Defects ◽  
Improved Design ◽  
Large Bone ◽  
Large Bone Defects

Bone tissue engineering currently represents one of the most interesting alternatives to autologous transplants and their drawbacks in the treatment of large bone defects. Mesenchymal stem cells are used to build new bone in vitro in a bioreactor. Their stimulation and our understanding of the mechanisms of mechanotransduction need to be improved in order to optimize the design of bioreactors. In this study, several geometries of bioreactor were analyzed experimentally and biological results were linked with numerical simulations of the flow inside the bioreactor. These results will constitute a base for an improved design of the existing bioreactor.

scholarly journals In Vivo Regeneration of Large Bone Defects by Cross-Linked Porous Hydrogel: A Pilot Study in Mice Combining Micro Tomography, Histological Analyses, Raman Spectroscopy and Synchrotron Infrared Imaging

Materials ◽  
2020 ◽  
Vol 13 (19) ◽  
pp. 4275
Author(s):  
Tetsuya Adachi ◽  
Francesco Boschetto ◽  
Nao Miyamoto ◽  
Toshiro Yamamoto ◽  
Elia Marin ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Bone Tissue ◽  
Bone Defects ◽  
Bone Diseases ◽  
Therapeutic Modality ◽  
3D Scaffold ◽  
Computed Tomography Scanning ◽  
Large Bone ◽  
Large Bone Defects

The transplantation of engineered three-dimensional (3D) bone graft substitutes is a viable approach to the regeneration of severe bone defects. For large bone defects, an appropriate 3D scaffold may be necessary to support and stimulate bone regeneration, even when a sufficient number of cells and cell cytokines are available. In this study, we evaluated the in vivo performance of a nanogel tectonic 3D scaffold specifically developed for bone tissue engineering, referred to as nanogel cross-linked porous-freeze-dry (NanoCliP-FD) gel. Samples were characterized by a combination of micro-computed tomography scanning, Raman spectroscopy, histological analyses, and synchrotron radiation–based Fourier transform infrared spectroscopy. NanoCliP-FD gel is a modified version of a previously developed nanogel cross-linked porous (NanoCliP) gel and was designed to achieve highly improved functionality in bone mineralization. Spectroscopic imaging of the bone tissue grown in vivo upon application of NanoCliP-FD gel enables an evaluation of bone quality and can be employed to judge the feasibility of NanoCliP-FD gel scaffolding as a therapeutic modality for bone diseases associated with large bone defects.

scholarly journals Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment

2021 ◽  
Vol 12 ◽  
Author(s):  
Weipeng Sun ◽  
Minying Li ◽  
Lei Xie ◽  
Zhexing Mai ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bone Defects ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Dosage Group ◽  
Active Ingredients ◽  
Large Bone ◽  
Large Bone Defects

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.

scholarly journals Harnessing extracellular vesicles to direct endochondral repair of large bone defects

2018 ◽  
Vol 7 (4) ◽  
pp. 263-273 ◽  
Author(s):  
E. Ferreira ◽  
R. M. Porter
Keyword(s):  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Bone Defects ◽  
Target Cells ◽  
Cell Sources ◽  
Near Term ◽  
Promising Source ◽  
Large Bone ◽  
Large Bone Defects

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation.Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.

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