Wednesday, March 12, 2008

Promotion of Osteogenesis in Tissue-Engineered Bone by Pre-Seeding Endothelial Progenitor Cells-Derived Endothelial Cells

This paper investigates the potential benefits of seeding endothelial cells onto tissue-engineered bone. Given a biocompatible scaffold and an osteogenic cell population, a vascular bed would help to overcome the difficulties of nutrient and oxygen transport in the 3D implant. The investigators tested their hypothesis that EC's help promote vascularization by using three test groups. First, osteoblasts and EC's were differentiated from the bone arrow of BALB/c mice. They used a porous polycaprolactone (PCL)-hydroxyapatite(HA) scaffold as the test implant.  One test group was the control (cell-free), one group was implants with only osteoblasts and the last group was implants with osteoblasts and EC's seeded onto it. The implants were placed in a 0.4cm long segmental femur defect. 

Evaluating the grafts histologically, the investigators found that after 6 weeks of implantation, the EC-OB group had a much more widely distributed capillary network. It also had osteoid generated by osteoblasts and ischemic necroses was absent. The conclusion of the paper is that pre-seeding implants with EC's did effectively promote neovascularization in grafts and improved osteogenesis while avoiding necrosis.
I believe this paper is important because it investigates methods of making tissue-engineered bone implants more effective in vivo. Now that scientists have found ways of making structurally sound scaffolds that are compatible with the body, the real challenge is to make this implant bioactive rather than just inert. This a key component to making tissue-engineered bone successful. 

5 comments:

Terry D. Johnson said...

Might also make a good 104 project.

Edward Sim said...

It seems that co-culturing of cells onto a scaffold is big theme in a lot of these new papers. The paper I posted also looked into culturing heart cells (cardiomyocytes)with endothelial cells and fibroblasts to improve vascularization in the engineered tissue, much like Yu was doing in the paper you posted. They hypothesize that the co-culturing could enhance certain receptors of both the ECs and the osteoblasts, so I was wondering why they didn't go ahead and do some sort of antibody assay (immunohistochemistry, elisa, western blot) to test this out. I was also wondering if the need for vascularization was more of a mass transport problem for building the tissue or to insure compliance with the host upon implantation. If it is a problem of diffusion of nutrients and oxygen to the seeded cells, I was wondering if they couldn't structure their scaffold (using parallel channels) for nutrient delivery. I really can't think of much else to say because I do think this was a well-performed experiment and an interesting read. Thanks Jackie.

Sisi said...

Interesting topic! It seems like one of the problems with a lot of the tissue-engineered transplants is the lack of vascularization, which means lack of nutrients. Vascularization of a tissue-engineered bone definitely solves a big part of the problem.

QWN said...

This is cool. I just went to an orthopaedics conference last week and there were a few studies on tissue-engineered bone with demineralized bone matrix (DBM) and bone matrix protein (BMP). I even got to mix my own 2mL sample of a BMP-7 putty that costs $5000. It's cool to see how our research finally end up in surgeons' hands.
A common bone cement used in orthopaedics today is calcium phosphate based. I know it is possible to seed the cement with cells before injecting into bones like vertebral bodies, but how long would it take for the cells to take over, the bone cement to degrade and vascularization to occur?

Christie Brown said...

Interesting idea. The paper I added to the blog showed that seeding a scaffold with lung progenitor cells prior to implantation in the lungs helped with the creation of new vasculature. This paper made me wonder if a combination of progenitor cells and ECs would have been even better at promoting growth of vasculature than progenitor cells alone.