Barrier
membranes for guided tissue regeneration are essential
for bone repair and regeneration. The implanted membranes may trigger
early inflammatory responses as a foreign material, which can affect
the recruitment and differentiation of bone cells during tissue regeneration.
The purpose of this study was to determine whether immobilizing interleukin
4 (IL4) on plasma immersion ion implantation (PIII)-activated surfaces
may alter the osteo-immunoregulatory characteristics of the membranes
and produce pro-osteogenic effects. In order to immobilize IL4, polycaprolactone
surfaces were modified using the PIII technology. No discernible alterations
were found between the morphology before and after PIII treatment
or IL4 immobilization. IL4-immobilized PIII surfaces polarized macrophages
to an M2 phenotype and mitigated inflammatory cytokine production
under lipopolysaccharide stimulation. Interestingly, the co-culture
of macrophages (on IL4-immobilized PIII surfaces) and bone marrow-derived
mesenchymal stromal cells enhanced the production of angiogenic and
osteogenic factors and triggered autophagy activation. Exosomes produced
by PIII + IL4-stimulated macrophages were also found to play a role
in osteoblast differentiation. In conclusion, the osteo-immunoregulatory
properties of bone materials can be modified by PIII-assisted IL4
immobilization, creating a favorable osteoimmune milieu for bone regeneration.