Tissue engineered bone

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Guy Sovak
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Tissue engineered bone

Just read very interesting article about Bone formation:

Journal of Biomechanics
Volume 40, Issue 2, 2007, Pages 399-411

Structural and nanoindentation studies of stem cell-based tissue-engineered bone

Gadi Pelleda, 1, Kuangshin Taib, 1, Dima Sheyna, Yoram Zilbermana, Sangamesh Kumbarc, Lakshmi S. Nairc, Cato T. Laurencinc, Dan Gazita and Christine Ortizb, Corresponding Author Contact Information, E-mail The Corresponding Author

aSkeletal Biotech Laboratory, Hebrew University, Hadassah Medical Center, Ein Kerem, Jerusalem 91120, Israel

bDepartment of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA

cDepartment of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22903, USA

Accepted 15 December 2005.
Available online 9 March 2006.

Abstract

Stem cell-based gene therapy and tissue engineering have been shown to be an efficient method for the regeneration of critical-sized bone defects. Despite being an area of active research over the last decade, no knowledge of the intrinsic ultrastructural and nanomechanical properties of such bone tissue exists. In this study, we report the nanomechanical properties of engineered bone tissue derived from genetically modified mesenchymal stem cells (MSCs) overexpressing the rhBMP2 gene, grown in vivo in the thigh muscle of immunocompetent mice for 4 weeks, compared to femoral bone adjacent to the transplantation site. The two types of bone had similar mineral contents (61 and 65 wt% for engineered and femoral bone, respectively), overall microstructures showing lacunae and canaliculi (both measured by back-scattered electron microscopy), chemical compositions (measured by energy dispersive X-ray analysis), and nanoscale topographical morphologies (measured by tapping-mode atomic force microscopy imaging or TMAFM). Nanoindentation experiments revealed that the small length scale mechanical properties were statistically different with the femoral bone (indented parallel to the bone long axis) being stiffer and harder (apparent elastic modulus, Enot, vert, similar27.3±10.5 GPa and hardness, Hnot, vert, similar1.0±0.7 GPa) than the genetically engineered bone (Enot, vert, similar19.8±5.6 GPa, Hnot, vert, similar0.9±0.4 GPa). TMAFM imaging showed clear residual indents characteristic of viscoelastic plastic deformation for both types of bone. However, fine differences in the residual indent area (smaller for the engineered bone), pile up (smaller for the engineered bone), and fracture mechanisms (microcracks for the engineered bone) were observed with the genetically engineered bone behaving more brittle than the femoral control.

Keywords: Gene therapy; Tissue engineering; Atomic force microscopy; Stem cells; Nanoindentation; Nanomechanics

Dominiquest
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You mentioned about

You mentioned about genetically engineered bone tissue.... I have a doubt regarding this.... We know that bone tissue is bone tissue, where ever you find it in the body, except for the difference in long bones and flat bones where the long bones have marrow....

now just imagine i've lost my femur... say i had bone cancer and I was operated and the bone was removed.... How exactly would the bone tissue culture give me back my femur with the marrow inside? Will the marrow form or will it be an empty bone? Also, will the strength of the new femur be the same as that of the old femur?

Guy Sovak
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That's a good Question that

That's a good Question that you raised,
First of all I imagine that they are not looking to replace the whole femur just parts of it at the beginning.
Now as you mentioned there are couple of different types of bones in our body but the very interesting thing is that no matter how they are initially formed be it through an endrochondral or interoseous formation the end result would be the same bone type either compact or spongy.
Again both of those types of bone compact or spongeous will have the same micro arrangements of Osteons etc.
As per the bone marrow issue, once again thats true the long bone have vascularisation coming from the vessels penetrating the peri and endoosteom this blood is not the same as the bone marrow but would supply the bone itself. I guess that the bone marrow could not be renewed at this point of time. But we have more then enough bone marrow in all of the other bones so even if the Femur would be replaced and would not have a bone marrow inside we will have more then enough for the renewal of or blood cells.
Guy

Dominiquest
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thank you for that insight...

thank you for that insight... I feel that a circumstance like bone cancer would rely on this type of treatment.... When you form the bone, do you use the parent cells from the same individual or do you find bone tissue and test for histocompatibility? If it is the latter, then how high are the chances for cancer to form again due to mild differences in the cells of host and foreign osteocytes?

Guy Sovak
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Once again another good

Once again another good question,
There are two ways to regrow bone, either with just using the bone material mainly HA (Hydroxiapetite) and other substances or by using the cell like was mentioned in the paper.
In the later I would say that you need to take under concideration the MHC. Then again there are transplantation in which you take a heart from one and plant it in another. The MHC is matched but still there is the need of drugs to maintain the autoimmune system depresed.
As you know in implantation of dental implants sometimes there is a need in implanting additional bone as the gingiva is to small and there is no place for the implant.
There where two ways to do it one with an autographt (bone taken from the same person ore using a bone bank.
In this case there is no needs for immunosupresent drugs as the bone was treated so it would not raise any immune response.
Guy

Dominiquest
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but there could still be

but there could still be chances for the oncogene to get activated. point mutations could occur in the grafted tissue cells during adjustment to the new environment, even when tissue is transplanted from one part of the body to another.

Guy Sovak
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This I am not sure.

This I am not sure.
If the bone is clean and clear from cancer the possibility for a point mutation is very small.
Guy

Dominiquest
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The reason I touched on caner

The reason I touched on caner is because of an incident and I was wondering if a mild fracture or damage to bone tissue can lead to cancer if left untreated for a long time.... and by long time i mean some years... is it possible to detect the cancer in an x-ray if there is no tumor formation?

Guy Sovak
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From what I know Bone cancer

From what I know Bone cancer can not be caused due to untreated fracture, opposite to that actualy couple of studies have shown that radiography could be one of the causes to bone cancer.
Yes bone cancer could be seen in X-ray and this is one of the diagnositc tools that is being use for the diagnosis of bone cancer.
the effected area due to bone cancer is seen a dark spot on the X-ray that look like holes in the bones.

Dominiquest
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Thank you for that.... The

Thank you for that.... The only reason I was afraid is because there is this boy in my neighborhood who injured his leg and left it untreated thinking it was a sprain when in fact there was a minor fracture and it developed into a cancer which is now causing him a lot of trouble and he is finding it really tough to recover from it... I had a mild injury in my left shoulder about 3 years back or so and it still gives me trouble... I have never taken a scan or an x-ray of the affected area and so the fear remains...