CORR Insights®: The Masquelet Technique: Can Disposable Polypropylene Syringes be an Alternative to Standard PMMA Spacers? A Rat Bone Defect Model

Where Are We Now?

The induced membrane technique described by Masquelet is an important tool for addressing large bone defects [4]. The potential advantages over its main alternative, bone transport, include that it uses surgical techniques that are familiar to most orthopaedic surgeons, that it is relatively inexpensive, and that it can be done with internal fixation, which is more familiar to most orthopaedists than external fixation. (Although some internal fixation options are now available for bone transport.) Overall, the induced membrane technique results in healing of the bone defects in 90% of adult patients. In pediatric patients, healing of the bone defect is not as reliable (60%-70% of patients), perhaps related to the frequency of bone defects secondary to tumor resection, which may present a more challenging healing environment than traumatic defects, which are more common in adults.

In the current study, Mathieu and colleagues [5] investigate the use of polypropylene as a spacer instead of polymethyl methacrylate (PMMA) in a critical defect model in rat femurs. They found that the use of either spacer material had similar characteristics of the induced membrane and healing of the bone defects as evaluated by radiographs, microCT, and histology. They concluded that the polypropylene syringe is a viable alternative spacer and may offer some practical advantages such as ease of use, ubiquitous availability, and absence of the exothermic reaction associated with PMMA polymerization.

This study raises the intriguing possibility that a polypropylene syringe—a simple, inexpensive, readily available material with no special handling techniques—could be used in place of PMMA as a spacer material in the induced membrane technique. There is already a report of a clinical application to affirm the feasibility of this approach [7]. Additionally, the hollow nature of the spacer could allow for the deposition of adjuvants (such as antibiotics) or collection of autologous wound factors that may be useful in the second-stage bone grafting, although these possibilities are areas for future investigation.

Where Do We Need To Go?

As is the case with many techniques in clinical medicine, much remains unknown about why the induced membrane technique is successful, even after almost 40 years of use [1]. Questions abound, including: How does the induced membrane support successful incorporation of the eventual bone graft? What are the necessary, sufficient, or ideal characteristics of the spacer? The graft? The fixation? What is the ideal timing (and what is the acceptable range of timing) of the second stage? Beyond that, could the procedure be reduced to a single stage using an implanted membrane [10]? Until some of these basic questions are answered, clinicians are left to follow dogma and rely on small case series.

The current study did answer some of the questions we had about this topic. With respect to timing, they found that it took 4 weeks to provide typical histologic organization of the membrane, maximal bone morphogenetic protein-2 staining, and the presence of mesenchymal stromal cells. This timing is consistent with clinical application of the technique, but is based on characteristics of the site rather than eventual bone healing. The choice of spacer material was the primary focus of the paper. A single alternative to PMMA, polypropylene, was evaluated. There are, however, several other materials and characteristics that have been evaluated, including titanium, polyvinyl alcohol sponges, and variations of surface texture [6].

How Do We Get There?

Many of the questions above may be addressed using small animal models. Specifically, the rat critical defect model appears to be most frequently used, although variations in methodologic detail and end points used as primary outcomes can make it difficult to compare across studies. Indeed, concerns have been raised about the impact of publications utilizing animal models as many studies fail to meet basic methodologic criteria (such as the Animal Research: Reporting of In Vivo Experiments guidelines). Further, many animal studies that are published are cited only once or never, suggesting that they may not have led to a subsequent publishable clinical or animal investigation [9]. To ensure efficient, impactful use of animals to address these research questions, a systematic approach with consistent methods for performing the model and evaluating outcomes could be developed through a multicenter collaboration. The evaluation should be robust and include biochemical, histologic, radiographic, and biomechanical end points with objective, blinded criteria [1]. Currently, the Orthopaedic Research Society has research sections that address specific topics, including one on preclinical animal models. They state on their website: “In conclusion, the use of animals requires greater, standardized rigor to both ensure the health and welfare of the animals as well as to provide the “best science” [8]. Now may be an opportunity for research organizations to take a more active role in not only reporting and promoting research, but also in driving quality and impact of research.

Securing funding for such preclinical studies can be challenging given that researchers are seeking to further define and refine an existing approach rather than exploring novel techniques [2]. Specifically, the Department of Defense (DOD) should have a particular interest in this area due to the large number of military personnel who suffer traumatic bone loss. There is precedent within the DOD and its Congressionally Directed Medical Research Programs to release funding opportunities aimed at specific conditions and requesting specific deliverables.

In the clinical setting, large randomized trials would be impractical due to the relative infrequency and the heterogeneity of cases requiring the induced membrane technique. Indeed, the Major Extremity Trauma Research Consortium (METRC) noted difficulty with recruitment when they published a randomized controlled study of tibial bone defects resulting from open fractures. Of 1123 patients screened at 16 trauma centers over 5 years, only 55 were eligible and only 34 consented to participate [3]. However, the problems are important enough and common enough (if defects of varying sizes, locations, and etiologies are included) that nonrandomized multicenter studies with prospective data collection may be warranted. Use of a validated system for classifying defects, agreed upon surgical techniques, predetermined definitions of complications, blinded radiographic evaluation, and validated outcome measures would all help strengthen the evidence produced. This might be accomplished with the aid of organizations such as the Orthopaedic Trauma Association, Arbeitsgemeinschaft für Osteosynthesefragen Foundation, or one of the existing large trauma research networks like METRC. Although it has been very difficult to conduct these studies in the past, two factors may lower the barriers. First is the development of very large multinational trauma consortiums such as Asociación de Cirujanos Traumatólogos de las Américas and The International Orthopaedic Multicenter Study, which may allow access to greater numbers of patients. These groups include sites and investigators from many low-income and low middle-income countries. These countries collectively represent large populations with a high burden of musculoskeletal trauma, which may result in larger numbers of patients who could benefit from a relatively low-cost intervention for bone defect repair like the induced membrane technique. Secondly, continued technological improvements in the ability to contact patients via mobile devices and to transmit data and images may make it easier to recruit and retain patients and for researchers to share and store data. If the power of such larger groups with access to so many patients could be harnessed in an efficient manner, it may provide an opportunity to succeed in an area where sufficiently large clinical studies have previously been very difficult to conduct.