Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Abstract

We and others have shown that changing surface characteristics of the spacer implanted during the first Masquelet stage alters some aspects of membrane development. Previously we demonstrated that titanium spacers create membranes that are better barriers to movement of solutes >70kDa in size than polymethyl methacrylate (PMMA) induced-membranes, and roughening creates more mechanically compliant membranes. However, it is unclear if these alterations affect the membrane’s biochemical environment or bone regeneration during the second stage. Ten-week-old, male Sprague-Dawley rats underwent an initial surgery to create an externally stabilized 6mm femoral defect. PMMA or titanium spacers with smooth (~1um) or roughened (~8um) surfaces were implanted. Four weeks later, rats were either euthanized for membrane harvest or underwent the second Masquelet surgery. Titanium spacers induced thicker membranes that were similar in structure and biochemical expression. All membranes were bilayered with the inner layer having increased factor expression (BMP2, TGFβ, IL6, and VEGF). Roughening increased overall IL6 levels. Ten-weeks post-engraftment, PMMA-smooth induced membranes better supported bone regeneration (60% union). The other groups only had 1 or 2 that united (9–22%). There were no significant differences in any microCT or dynamic histology outcome. In conclusion, this study suggests that the membrane’s important function in the Masquelet technique is not simply as a barrier. There is likely a critical biochemical, cellular, or vascular component as well.

Evaluation of global gene expression in regenerate tissues during Masquelet treatment

“…Alternatively, the spacer may promote more active bone healing and cortical vitality as a result of the mechanical pressure put onto the cut bone surfaces by the spacer. Indeed, during the second phase of Masquelet, bone formation appears to initiate from the cut bone ends and not from the center IM 40 . Thus, our results may suggest that the bone ends in the Masquelet are “primed” for regeneration, and thus able to respond favorably to autograft when placed during the second stage.…”

“…Osteoblasts are a component of an IM that forms around PMMA placed in bone, but not the membrane that forms around PMMA placed in a subcutaneous pocket 14 . Accordingly, the IM contains markers of osteoblasts and bone regeneration including BMP2, TGFβ, RUNX2, vascular endothelial growth factor, interleukin‐6, and STRO‐1 11,12,14,40 . The membrane also contains osteoclasts 10 .…”

“…The membrane also contains osteoclasts 10 . Islands of calcification have been documented in the membrane induced in rodent models of Masquelet 10,11,40,42 and in biopsies of IM harvested from human patients 3 . Cellular and growth factor content of the IM diminish with time as it becomes more ECM rich and fibrotic; however, the impact of this decrease on outcomes poststage second surgery is not known 3,14 …”

Masquelet Technique: Effects of Topical Mechanical Stability on the Formation of Masquelet Membrane in a Rabbit Radial Defect Model

“…There were many researches regarding that the stability of fracture broken end directly affects the healing of bone fracture (25)(26)(27)(28). While during the first phase of Masquelet, the bone defects filling with PMMA spacer are fixed with internal plate, intramedullary nail, external fixator, casting, or nothing (17,(19)(20)(21). Each fixed mode could result in a different mechanical environment, subsequently have significant influence on bone repair.…”

“…During the first phase of Masquelet, the bone defects filling with bone cement (polymethyl methacrylate, PMMA) spacer are fixed with internal plate, intramedullary nail, external fixator, casting, or nothing (12,17,(19)(20)(21). But it is not sure that which fixation method is more appropriate for membrane formation in the first stage of Masquelet (13,(22)(23)(24).…”