Tuesday, March 13, 2007

Bone modeling adaptation as a method for promoting development of bone tissue engineered construct in vitro

Zhang Chunqiu, Zhang Xizheng, Dong Xin and Zhu Weimin
School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300191, China
Tianjin Institute of Medical Equipment, Tianjin 300161, China
Department of mechanics, College of Mechanical Science and Engineering, Nanling Campus, Jilin University, Changchun 130022, China

Received 11 September 2006; accepted 18 September 2006. Available online 22 January 2007.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WN2-4MW90G9-1&_user=4420&_coverDate=01%2F22%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000059607&_version=1&_urlVersion=0&_userid=4420&md5=0846f3e0f7263064a1b3a422f48ea9ff

This paper focuses on using the bone modeling adaptation to promote the development of a bone tissue engineered construct in vitro. It is found that in the modeling process, in vivo bone formation increases bone formation in order to adapt to overload strains. So, this fact is taken advantage of in the lab as external mechanical forces are applied onto cell-seeded scaffolds to produce overload strains in the in vitro constructs. This produces bone cell differentiation and extracellular matrix deposition, which initiates bone formation on the interior of the scaffolds. The development of the construct is produced step by step as it accomodates itself to the new mechanical environment. Once the full bone construct is produced, these can be used as innovative off the shelf, bone-like substitutes for patients who suffer from long-term bone defects.

The cells that deposit themselves on the interior of the scaffold in the development of BTEC include osteocytes, bone lining cells, osteoblasts and osteoprogenitors. When the base of the template becomes filled with a large amount of osteocytes, the construct then matches native bone tissue very well and can be the BTEC desired by surgeons for use in replacing defected bone. Scaffold strains induced by the mechanical demands placed on the construct in vitro serve to produce a mechanical environment that is similiar to native tissue. The stains include everything from deformations of bone cells stuck on the interior surfaces of the scaffold to force induced stimuli such as flow shear, flow potential and even changes of signaling molecules, nutrients, and waste products. In the development of the BTEC, osteocytes direct osteoblasts to decide the location where it is mechanically neccessary for more bone tissue to be added. These osteocytes then become thicker within the construct and the bone-like construct can finally withstand strong forces after a long period of time.

This introduced model for creating bone-like constructs than can be used as substitues for native bone tissue holds great value for medicinal uses because present autologous bone grafting presents several drawbacks. Its limitations include the limited available amount for transplantation, the lack of structural integrity to withstand functional loads, and increased patient morbidity at the site of harvest. Production of off the shelf bone-like substitutes is still a major challenge even if the proper scaffolds, engineered cells and growth factors are given, but the bone modeling adaptation seems to be promote the development of BTEC in vitro rather well. Hopefully, in the future, this method can be used to promote the widespread use of tissue engineered bone-like substitutes to replace current autologous grafting methods.

5 comments:

kzhang said...

in your discussion you mentioned mechanical strains. does the paper discuss how these strains cause interstitial fluid flow in the bone matrix to be capable of increasing mass transport of signaling molecules, nutrients, ...?

Henry Lu said...

i think modeling systems like this can be very valuable for NASA, especially for their planned mars mission. with a 3 year round trip timetable, a modeling system like this can probably determine whether such astronaunt's bones would simply break due to years in 0g env.

Eric Huang said...

The strains can cause many effects on osteocytes. The strains that are detected by osteocytes induce biological signals which induce effector cells to regulate bone tissue. The interstitial fluid flow has been proposed to be capable of increasing transport of nutrients and signaling molecules as well as ensuring osteoblast viability.

Eric Huang said...

I'm not so sure it could be used to determine whether astronaut's bones would simply break due to their time in space. However, it could be used to medicinally to replace astronaut's bones after they have gone to Mars and back and tortured their bones.

JerLin said...

An osteosome is the smallest quantum unit of bone that has all of the properties of bone (extracellular matrix, bone matrix proteins, and mineralized matrix, etc; there is a full table in the following mentioned paper that lists all of the requirements of an "osteosome"). It was termed in a minireview paper, "Bone Morphogenesis and Modeling: Soluble Signals Sculpt Osteosomes in the Solid State" by AH Reddi.

What is the timescale for a procedure such as this? Also, would it be wise to produce off the shelf scaffolds such as these? Improper matching of stiffnesses between the scaffold and the patient's actual bone stiffness could cause stress-shielding, leading to further bone loss.