Wednesday, September 6, 2017

Musculoskeletal tissue banking

Biological properties of musculoskeletal allograft

This lecture focused more on the "skeletal" grafts than the "musculo-" grafts. Bone grafts are often used in situations where there is bone loss, such as in joint replacement, infections and fractures. They can be derived from living donors (usually from femurs from hip replacement surgery- the femoral head is usually discarded) or from cadavers.

Osteoconduction vs osteoinduction
Interaction between growth factors and osteoblasts

Osteoconduction and osteoinduction are both desirable traits of a bone graft. Osteoconduction means that the bone will be able to grow through the scaffold provided by the graft, and osteoinduction means that the graft can promote bone growth. Osteoinduction can be either active or passive: active osteoinduction is due to growth factors (usually bone morphogenic proteins, or BMPs), and passive osteoinduction is due to other environmental or morphological factors. Another important trait for grafts is osteointegration, which is the ability of a graft to integrate into the recipient's bone.

Autograft vs allograft vs xenograft

An autograft uses a patient's own bone, which is obviously pretty ideal (non-immunogenic, will be osteoconductive, osteoinductive and osteogenic, and so on). The bone that is most likely to be used is the iliac crest. Autografts do have problems, however: the donor site might have problems, and longer surgery times might be needed. Autografts might not be suitable for some larger grafts, where structural strength is needed.

An allograft is a graft from another human. There are many types. Allografts are osteoconductive, but they are not osteogenic (which I think means that they don't undergo normal bone growth in this case) and only have limited osteoinduction capacity. There may also be some issues with immunogenicity.

Demineralised bone matrix (DBM) is a type of allograft that has been exposed to strong acids, removing the mineral parts (mainly calcium). It is not osteogenic, but is osteoconductive and has varying capacity for osteoinduction. Unfortunately, it is expensive and lacks structural integrity.

OP-1 implants, which are basically just recombinant BMP-7, have been trialled. Not much else was said about them during the lecture, however.

Other options that have been trialled are xenografts (grafts from different animals) and synthetic materials. Again, I don't have much more to add here.

Reducing bioburden: process controls & terminal irradiation
Appreciate the importance of the quality system 

It takes around 3-7 months to prepare a cadaver-derived graft for transplantation, and around 8-12 months to prepare a graft from a living donor. Many different process controls are implemented in order to ensure that the graft is as good as possible (you wouldn't want to accidentally graft a tumour into someone, for instance). Firstly, grafts are excluded if they contain malignancies or certain autoimmune diseases. Preparation is done in a Grade C cleanroom, which is kept clean via Hepa filters, particle counting, pressure gradients and environmental monitoring. Grafts are tested for microbes and irradiated to kill basically everything on them. (The high-dose irradiation also means that HLA matching isn't really necessary for bone grafts.)

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