Man carrying his jaw on his back

Nice name for a thriller, right? But it’s no more horrible news. That’s how plastic surgery steps into new promising technologies.

The jaw placed on latissimus dorsi. Picture taken 3 weeks after implantation. By P.H.Warnke et al.

This is the case about collaboration of two fiercely developing fields — bioengeneering and reconstructive surgery. Plastic surgery offers us different kinds of manipulations to restore tumor defect, such as fibula autotransplant, scapula, iliac crest, or rib transplant. Being very effective in reconstruction of recepient area, this method still leaves a skeletal defect in the donor zone, which itself is associated with serious morbidity. Authors (P H Warnke, I N G Springer, J Wiltfang, Y Acil, H Eufinger, M Wehmöller, P A J Russo, H Bolte, E Sherry, E Behrens, H Terheyden) suggest another kind of treatment: by using three-dimensional computed tomography (CT) scanning and computer-aided design techniques there was made an ideal virtual replacement for the mandibular defect. Than these data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 (BMP7) and 20 mL of the patient’s bone marrow. The latter consisting of undifferentiated precursor cells was provided as a target for recombinant human BMP7.

BMP7 is an osteoinductive factor that initiates conversion of undifferentiated precursor stem cells into osteoprogenitor cells, which produce mature bone. In 2001 use of recombinant human BMP7 in prefabrication of bone grafts received an approval from Therapeutic Goods Administration (Department of Health and Ageing, Australia).

Necessary to mention, that this protein plays significant role not only in bone, but also in kidney and brown adipose tissue development. Recent research (by Monsivais D et al.) also reveals such features of BMP7 as being an important factor during the process of implantation that contributes to healthy embryonic development. Protein is broadly involved in normal embryo development and also in abnormal pathological process such as cancer. Precise study was performed by Hu M et al., where they investigate how different forms of BMP family affect differentiation and migration of squamous cancer esophageal cells. BMP6/7 overexpression increased ECA-109 cell invasion and metastasis, while BMP2/4 overexpression reduced it. No doubt molecular mechanisms of this protein should be further investigated to get a deep view in vital processes of our organism.

In current article BMP7 was applied to a 56-year-old man, who had received ablative tumour surgery 8 years previously in the form of a subtotal mandibulectomy. Resection was made from paramedian left region to the retromolar right region. Size defect of more than 7 cm had been bridged with a titanium reconstruction plate since initial surgery. After that patient underwent radiation treatment (total dose 66 Gy).

After a teflon model was created that matched the virtual mandible exactly, a titanium mesh scaffold was then formed onto the model, which was subsequently removed and the remaining titanium mesh cage was filled with ten bone mineral blocks as carriers. Then 7 mg recombinant human BMP7 embedded in 1 g bovine collagen type 1 coated mineral blocks. 20 mL aspirated bone marrow cells (from iliac crest) were mixed with 5 g natural bone mineral of bovine origin (particle size 0·5–1·0 mm) and this mixture was used to fill the gaps between the blocks inside the cage.

After all those procedures surgeons took the lead. Titanium mesh was implanted into a pouch of the patient’s right latissimus dorsi muscle. According to the authors, the patient did not complain of pain or sleep disturbance and relayed only minor concerns about the range of motion of his arm.

4 weeks postoperatively, skeletal scintigraphy was done: bone remodelling with vital osteoblasts was detected inside the implant, verified by a tracer enhancement. Also CT of the thorax gave radiographic evidence for bone formation around the implant site.

7 weeks postoperatively, the patient underwent transplantation of the mandibular replacement. In the article it is remarked that minor bone overgrowth on the ends of the replacement was curetted to fit the transplant easily into the defect, but no further correction of the shape or form of the graft was needed.

On 11th postoperative day (after second surgery) skeletal scintigraphy was made and showed continued bone remodelling and mineralisation inside the mandibular transplant, indicating undisturbed vascular perfusion and survival of the induced bone cells.

After transplantation of bone replacement

By the 4th week post-transplantation the patient enjoyed his first dinner in 9 years (bread and sausages); before reconstruction he had only been able to eat soft food and soup, now he is able to undertake a small amount of mastication. The patient is also satisfied with the aesthetic outcome of the procedure.

That seems to be part of fantastic film, but bioengeneering appears to be really perspective method of bone regeneration, and more and more studies approve it. Capacious diagram (article in the link) below shows what the variety of mesenchymal stem cells use in bone healing, and also moves us to improving knowledge, looking through MSC protocols which could be investigated further to aid the use of MSCs in clinical practice.

In conclusion, take home message: dream big, nowadays new technoligies and perspective opportunities serve us to apply academic knowledge mixed with fresh ideas and ambitious plans to clinical practice. Try, investigate, make mistakes and repeat. There is always a result we get. And one of them will hit the 10th point mark for sure.