Reconstruction of critical-size bone
defects (CSDs) in the craniomaxillofacial
(CMF) region remains challenging. Scaffold-based bone-engineered constructs
have been proposed as an alternative to the classical treatments made
with autografts and allografts. Scaffolds, a key component of engineered
constructs, have been traditionally viewed as biologically passive
temporary replacements of deficient bone lacking intrinsic cues to
promote osteogenesis. Nowadays, scaffolds are functionalized, giving
rise to bioactive scaffolds promoting bone regeneration more effectively
than conventional counterparts. This review focuses on the three approaches
most used to bioactivate scaffolds: (1) conferring microarchitectural
designs or surface nanotopography; (2) loading bioactive molecules;
and (3) seeding stem cells on scaffolds, providing relevant examples
of in vivo (preclinical and clinical) studies where
these methods are employed to enhance CSDs healing in the CMF region.
From these, adding bioactive molecules (specifically bone morphogenetic
proteins or BMPs) to scaffolds has been the most explored to bioactivate
scaffolds. Nevertheless, the downsides of grafting BMP-loaded scaffolds
in patients have limited its successful translation into clinics.
Despite these drawbacks, scaffolds containing safer, cheaper, and
more effective bioactive molecules, combined with stem cells and topographical
cues, remain a promising alternative for clinical use to treat CSDs
in the CMF complex replacing autografts and allografts.