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 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

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

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.

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.

Application of nanoparticles in bone tissue engineering; a review on the molecular mechanisms driving osteogenesis

2021 ◽  
Author(s):  
Azam Bozorgi ◽  
Mozafar Khazaei ◽  
Mansoureh Soleimani ◽  
Zahra Jamalpoor
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Bone Defects ◽  
Large Bone ◽  
Large Bone Defects

The introduction of nanoparticles into bone tissue engineering strategies is beneficial to govern cell fate into osteogenesis and the regeneration of large bone defects. The present study explored the role...

Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering

2010 ◽  
Vol 368 (1917) ◽  
pp. 2065-2081 ◽  
Author(s):  
J. Venugopal ◽  
Molamma P. Prabhakaran ◽  
Yanzhong Zhang ◽  
Sharon Low ◽  
Aw Tar Choon ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Natural Polymer ◽  
Natural Polymers ◽  
Biomimetic Hydroxyapatite ◽  
Large Bone ◽  
Large Bone Defects

The fracture of bones and large bone defects owing to various traumas or natural ageing is a typical type of tissue malfunction. Surgical treatment frequently requires implantation of a temporary or permanent prosthesis, which is still a challenge for orthopaedic surgeons, especially in the case of large bone defects. Mimicking nanotopography of natural extracellular matrix (ECM) is advantageous for the successful regeneration of damaged tissues or organs. Electrospun nanofibre-based synthetic and natural polymer scaffolds are being explored as a scaffold similar to natural ECM for tissue engineering applications. Nanostructured materials are smaller in size falling, in the 1–100 nm range, and have specific properties and functions related to the size of the natural materials (e.g. hydroxyapatite (HA)). The development of nanofibres with nano-HA has enhanced the scope of fabricating scaffolds to mimic the architecture of natural bone tissue. Nanofibrous substrates supporting adhesion, proliferation, differentiation of cells and HA induce the cells to secrete ECM for mineralization to form bone in bone tissue engineering. Our laboratory (NUSNNI, NUS) has been fabricating a variety of synthetic and natural polymer-based nanofibrous substrates and synthesizing HA for blending and spraying on nanofibres for generating artificial ECM for bone tissue regeneration. The present review is intended to direct the reader’s attention to the important subjects of synthetic and natural polymers with HA for bone tissue engineering.

scholarly journals Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2687
Author(s):  
Venkata Suresh Venkataiah ◽  
Yoshio Yahata ◽  
Akira Kitagawa ◽  
Masahiko Inagaki ◽  
Yusuke Kakiuchi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Defects ◽  
Significant Loss ◽  
Osteogenic Potential ◽  
Large Bone ◽  
Large Bone Defects

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.

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