Probing the role of methyl methacrylate release from spacer materials in induced membrane bone healing

Stahl, Alexander; Park, Young Bum; Park, Sang-Hyun; Lin, Sien; Pan, Chi-Chun; Kim, Sungwoo; Yang, Yunzhi P.

Affiliations

¹Department of Orthopaedic Surgery, Stanford University, Stanford, California, USA

²Department of Chemistry, Stanford University, Stanford, California, USA

³Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, South Korea

⁴Osong Research Institute, TaeWoong Medical Co., Ltd, Gimpo, South Korea

⁵Department of Mechanical Engineering, Stanford University, Stanford, California, USA

⁶Department of Materials Science and Engineering, Stanford University, Stanford, California, USA

⁷Department of Bioengineering, Stanford University, Stanford, California, USA

Abstract and keywords

In the induced membrane (IM) technique for bone reconstruction, a poly(methyl methacrylate) (PMMA) spacer is implanted to induce formation of a foreign body membrane around the defect site. Membrane development is essential for later bone grafting success, yet the mechanism by which the IM promotes bone regeneration remains unknown, as are the ways that spacer composition plays a role in the membrane's healing potential. This study investigated the impact of leached methyl methacrylate (MMA)—the major monomeric component of PMMA—on IM development. In vitro cell culture found that MMA elution did not impact endothelial cell or mesenchymal stem cell proliferation. For in vivo analysis, we advanced a streamlined rat femoral model to efficiently study the influence of spacer properties on IM characteristics. Comparison of membrane formation around polycaprolactone (PCL), MMA-eluting PCL (high-dose PCL-MMA and low-dose PCL-MMA), and surgical PMMA revealed robust membranes enveloped all groups after 4 weeks in vivo, with elevated expression of osteogenic bone morphogenetic protein-2 and angiogenic vascular endothelial growth factor compared with the surrounding muscle and bone tissues. Growth factor quantitation in IM tissue found no statistically significant difference between groups. New bone growth, vascularization, and CD163+ macrophage populations surrounding the polymer implants were also quantified; and blood vessel formation around high-dose PCL-MMA was found to be significantly decreased compared with PCL alone. To the best of our knowledge, these findings represent the first time that results have been obtained about the characteristics of membranes formed around PCL in the IM setting.

Keywords: bone regeneration; induced membrane; Masquelet technique; methyl methacrylate; rat model

Links

DOI: 10.1002/jor.25147

PubMed: 34314063

WoS: 000684826100001

History

Received: 2021-02-09

Revised: 2021-06-30

Accepted: 2021-07-14