Overview

Most of our primary projects revolve around understanding and improving an orthopaedic surgical treatment called Masquelet’s Induced Membrane Technique (MIMT). Also listed are collaborative projects that are primarily conducted in another lab but we contribute our expertises to a significant portion – typically in the aspects involving determining bone structure and strength (e.g. microCT, bone histology, and mechanical testing).

MIMT Basics

Most Masquelet’s Induced Membrane Technique (MIMT) is a two-staged surgical technique to reconstruct segmental bone defects (i.e. >2.5cm in long bones). During an initial surgery, the damaged/diseased tissue is removed, fixation is implanted to provide stability, and the bone defect is filled with a bone cement spacer. The spacer initiates the foreign-body response cascade eventually resulting in the spacer being encased in an autologous membrane. Weeks to months later during a second surgery, the spacer is removed and the resulting membrane compartment is filled with morselized bone graft (i.e. ground up bone matrix and bone marrow). The graft remodels over the following months so that most patients are considered healed in 8 to 12 months regardless of defect size.

The technique can heal defects as large as 25 cm, more than triple the traditional maximum volume treatable via grafting without the membrane. Such great success in extraordinary situations, combined with technical simplicity and ease on clinicians and patients, has made the little-known technique increasingly popular – especially in low resource environments. However, success rates are not ideal (~86%, ~90% with revision grafting), and the mechanisms driving success or failure are completely unknown. Thus some surgeons still prefer to use the more arduous alternative treatment distraction osteogenesis which has a success rate of ~95%.

If the mechanisms can be discovered, it will provide evidence to guide surgical decisions, to develop diagnostical tools which can determine “readiness”, and to create adjuvant treatments to help non-responders. Additionally, we are hopeful the biological mechanisms discovered in this extreme repair scenario can be applied to other anabolic bone situations like fracture non-union, spinal fusion, or implant integration.

Project 1 – Development of a Mouse Model of MIMT

A major hurdle for testing potential mechanisms of MIMT is that all of the current animal models are in rat or larger species. The number of transgenic tools and reagents available for mice far out number those available for rats. There are essentially none or very few for larger species like rabbit, pig, or sheep. The main goal of this project is to develop a mouse model of MIMT so that more sophisticated mechanistic experiments can be performed using transgenic mouse lines. Secondarily cutting edge RNA sequencing technologies will be employed to comprehensively catalogue the membrane’s cell populations and gene expression. After establishing that MIMT healing is possible in a mouse, we will compare the membrane’s cell populations, gene expression, protein content, and morphology at 2 time points to what is already known in rats, humans, and larger animals. Then we will use existing transgenic mouse lines to trace host/graft cells as well as host/graft osteoblasts during the second stage. In sum, the results from this work will be used to select novel candidate pathways for future study and help determine which cells should be targeted for this manipulation.

Project 2 – Evaluation of an Multifunctional Electrospun Wrap for MIMT

Over 50% of adults undergoing MIMT have osteomyelitis (aka a bone infection). Clearing the infection is vital for graft survival and bone reconstruction. At the same time, it is widely hypothesized that inadequate membrane mechanical strength and vascularity cause MIMT non-union. Our ongoing collaboration with the Cosgriff-Hernandez Lab at University of Texas at Austin tests an electrospun spacer wrap fabricated with their innovative fabrication methods that has increased handibility, antimicrobial properties, and immune modulating benefits in MIMT. We anticipate the wrap will reduce infection while also increasing membrane mechanical strength and biological activity.