Designer Tissue-engineered Bone Scaffolds in the Mandible: Are We There Yet?

Critical-sized mandibular defects necessitate surgical repair. With worldwide oral cancer incidence rates rapidly rising, more patients are likely to require mandibular reconstruction post-oncological resection (1). The current gold standard, autografting, invariably creates another skeletal defect and relies on the quality of autogenous bone available. There has been much interest in scaffold freeform fabrication (SFF), a tissue-engineering (TE) technique involving de novo layer-by-layer reconstruction of bespoke three-dimensional porous bone scaffolds (2). Direct SFF involves fabricating the desired object, as opposed to the indirect method, which involves creating a bespoke mould of the desired object. We aimed to systematically review the state-of-the-evidence for SFF in repairing mandibular defects in vivoand assess whether it is currently a viable alternative to autografting and conventional TE approaches.

A comprehensive electronic literature search of the MEDLINE and ISI Web of Knowledge databases was performed. All study methodologies, including preclinical in vivo and clinical literature regarding SFF for the repair of mandibular bone defects were systematically reviewed. Inclusion criteria were: (i) studies must have implemented the direct SFF method; (ii) studies must have surgically implanted the SFF scaffold into the mandible of the subject(s). The primary outcome measure was evidence of new bone growth, regardless of whether this was ascertained clinically, radiographically or histologically. Secondary outcome measures were occlusion and temporomandibular joint (TMJ) function.

281 records were identified through database searching after duplicates were removed. 6 studies (4 animal and 2 human studies) were deemed suitable that met the inclusion criteria. Hydroxyapatite was the most commonly used scaffold material in animal studies(n=3). All animal studies showed substantial bony ingrowth, with two demonstrating cartilage formation along the condylar articular surface. Both human studies showed acceptable occlusion with post-operative increase in mouth opening and decreased mouth opening deviation, although one demonstrated suboptimal TMJ function. 

Our systematic review demonstrates SFF scaffolds have produced good bony ingrowth in animal studies, although there is a paucity of comparative data to current gold standards. There are limited but promising reports of good functional outcome in preliminary studies in humans. The level of control of internal and external scaffold architecture in SFF is clearly highly desirable, however the challenges of ensuring adequate surgical training and economic feasibility need to be addressed. With such limited data thus far, SFF is not currently as a viable alternative to autografting, however the results thus far have been promising and should serve as a stimulus for further research.

1.    Mistry M, Parkin DM, Ahmad AS, Sasieni P. Cancer incidence in the United Kingdom: projections to the year 2030. British Journal of Cancer. Nature Publishing Group; 2011 Oct 27;105(11):1795–803.

2.    Hutmacher DW, Sittinger M, Risbud MV. Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends in Biotechnology. 2004 Jul;22(7):354–62.