In Vivo Engineering of Organs: The Bone Bioreactor
Molly M. Stevens, Robert P. Marini, Dirk Schaefer, Joshua Aronson, Robert Langer, and V. Prasad Shastri
Proc Natl Acad Sci USA 2005 August 9; 102(32): 11450-11455.
Although bone continues to remodel throughout lifetime, people with different conditions will have different bone regeneration capacity. For example, the bone regeneration capacity of older people tends to be slower than younger people. So it is very important to have effective treatment for large bone defects. Since in vitro engineering of bone tissue is very challenging and it encounters many problems. The most common treatment nowadays for large bone defects is by harvesting new bones in the crest of the iliac. Not only is autologous bone very good at integrating with the host bone, it also does not contain any immune-related problems. But there are many downsides of this method such as limited supply of autologous bone, long-term pain from the crest of the iliac and bone morbidity. This research paper is about a study of bone formation/growth in a bone bioreactor in vivo.
The hypothesis of the experiment is that functional bone tissue can be harvest by creating a space between the surface of a long bone and periosteum (a membrane that's rich in pluripotent cells) because all necessary cells and biomolecular signals for bone formation are delivered locally to the bioreactor and they greatly enhance the bone formation. This hypothesis is investigated by using New Zealand White rabbits. First, the experimenter creates a bone bioreactor in the tibia of the rabbit by injecting biocompatible calcium-alginate gel that's crosslinked. Then after 6 weeks of the creation of bioreactor, autologous bone tissues are transplated into the bioreactor and harvest for many weeks. Then the bone is transplanted to the defects. At the end, the experimenter also testes how good the bone samples function by using Merlin Materials Testing Software.
The result of this experiment proves its hypothesis. After creating a bioreactor between the surface of long bone and periosteum, cells quickly proliferate inside periosteum and the bioreactor space is filled with periosteal cells and capillaries. Then woven bone is formed after 2 weeks and it turns into compact bones later in time. This kind of bone formation process is quite different from the usual process which involves the formation of fibroblasts scar tissue. Beside testing the effectiveness of bone formation in bioreactor, the experimenter also study the functionality of newly formed bone. The result is that the newly formed bone is the same as other bones and it has the same functions. In this paper, the experimenter also discuss results of bone regeneration from different modified bioreactor. These discussions are very useful to understand more about the bone regeneration in bioreactor such as the necessary conditions etc.
The reason why I chose this paper is because I am very interested in bone regeneration. Since I and some of my friends have minor bone fracture for quite a long while already, but still the fracture has not recover and so I am very interested in the treatment of bone defects. After reading this paper, I found this method of bone regeneration in vivo bioreactor very useful. Not only it is effective, also it is less painful if we compare it to the harvesting in the crest of iliac. I think we should definitely study more about it and maybe carry out clinical trials to see if it really works or not.
8 comments:
This is good. I liked the papers that you and Angela chose regarding bone regeneration. I wonder what other ways, though, the group might have tested newly-formed bone functionality.
I suppose tensile checks/ shear stress/bulk modulus/ability to rapidly integrate in existing bone structure. Do you have any other ideas?
To anglee,
They actually tested how well the newly-formed bone integrate with an existing one, and the result is they integrate quite well too.
Besides the software that's discussed in the paper, I think if we know a specific function of a part of the newly formed bone, we can test how well they do that function.
Before clinical trials are performed, should scientists investigate the possibility that the creation of the bioreactor might cause some sort of pain or discomfort? Also, what would the total timeline look like if one were to receive this treatment for bone defects?
I am interested in the materials that were used in this experiment. You say a crosslinked gel was implemented in to the bone for tissue growth. I'm wondering what other properties the gel had, and if the paper that you read had any explanation on its particular selection. Why not a PLA scaffold or hydroxyapetite ceramics used (since they are more accepted in industrial terms and have shown to be osteoconductive, respectively)? Is there something special about the gel that made it specific towards the type of experiment performed?
It appears that we ended up picking the same paper! I definitely thought this paper was convincing to me that in-vivo engineering of tissue is the way to go. Of course with the advantages of autologous transplantation comes the drawbacks: the time required to culture these cells when the transplantation is needed asap, and the potential invasive procedures required to harvest then transplant the bone (when actual clinical trials must be conducted).
A few questions were asked to me regarding the necessity of such a method. I proposed a few answers, but if you can take a look at response to my comments and can come up with some good suggestions, that would be great! The main question is: why culture these cells elsewhere in the body and not directly on the injured site?
This is a very interesting way of getting around the replacement bone issue, since only so much autologous bone can be removed and other substitutes always have major drawbacks. I wonder what the clinical practicality of the procedure is (ie. just how much extra bone can be grown, or how painful this procedure is); this could be a really cool new way to produce bone implants!
I agree this technique is very useful, since the body won't reject "part of itself". Hope they will continue to carry out experiments on some other animails.
Besides, I wonder whether this method can be extended to other kind of tissue such as blook vessel and muscle.
Post a Comment