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Studying Normal Tissue Radiation Effects using Extracellular Matrix Hydrogels
Published on: July 24, 2019
Comparative study of membranes induced by PMMA or silicone in rats, and influence of external radiotherapy
Erwan de Monès1, Silke Schlaubitz2, Hugo Oliveira3
1INSERM U1026, Tissue Bioengineering, 146 rue Léo-Saignat, F-33000 Bordeaux, France; Univ. Bordeaux, 146 rue Léo-Saignat, F-33000 Bordeaux, France; Department of Otolaryngology - Head and Neck Surgery, Univ. Bordeaux, Place Amélie Raba Léon, F-33000 Bordeaux, France.
Abstract:
The induced membrane technique has been used for long bone defect reconstruction after traumatism. One of the major drawbacks of this method is the difficult removal of the polymethyl methacrylate spacer after membrane formation. We therefore replaced the stiff PMMA spacer with a semi-flexible medical grade silicone spacer. This study aimed to compare subcutaneously formed membranes, induced by PMMA and silicone, in the irradiated or not irradiated areas within 28 rats that received the spacers. Histological analysis was performed to evaluate the composition of the membrane and to quantify the amount of vessels. Histomorphometric measurements were used to evaluate membranes' thickness, while fibrosis and inflammation were scored. The expression of VEGF and BMP-2 in lysates of the crushed membranes was determined by Western blotting. ALP expression was analyzed in HBMSC cultures in contact with the same lysates. Non-irradiated membranes induced by the two spacer types were non-inflammatory, fibrous and organized in layers. Irradiation did not change the macroscopic properties of membranes that were induced by silicone, while PMMA induced membranes were sensitive to the radiotherapy, resulting in thicker, strongly inflammatory membranes. Irradiated membranes showed an overall reduced osteogenic potential. Medical grade silicone is safe for the use in radiotherapy and might therefore be of great advantage for patients in need of cancer treatment.
Insights
Replacing stiff polymethyl methacrylate (PMMA) spacers with medical-grade silicone in induced membranes for bone defect reconstruction offers advantages. Silicone spacers are safe for radiotherapy, unlike PMMA, which can cause inflammation and reduce bone healing potential.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Orthopedic Surgery
Background:
- The induced membrane technique is crucial for long bone defect reconstruction.
- Polymethyl methacrylate (PMMA) spacers present challenges in removal after membrane formation.
- Semi-flexible medical-grade silicone spacers offer a potential alternative to PMMA.
Purpose of the Study:
- To compare the characteristics of membranes induced by PMMA versus silicone spacers.
- To evaluate the impact of radiotherapy on these induced membranes.
- To assess the safety and efficacy of silicone spacers in irradiated environments.
Main Methods:
- Subcutaneous implantation of PMMA and silicone spacers in 28 rats.
- Histological analysis of induced membranes for composition, vascularization, thickness, fibrosis, and inflammation.
- Western blotting for VEGF and BMP-2 expression.
- Alkaline phosphatase (ALP) expression analysis in human bone marrow-derived stem cell (HBMSC) cultures.
Main Results:
- Non-irradiated membranes from both spacer types were organized and non-inflammatory.
- Silicone-induced membranes remained stable after irradiation.
- PMMA-induced membranes became thicker, inflammatory, and showed reduced osteogenic potential post-irradiation.
- Irradiated membranes exhibited an overall reduced osteogenic potential.
Conclusions:
- Medical-grade silicone is a safe and effective alternative to PMMA spacers for induced membrane formation, especially in patients undergoing radiotherapy.
- Silicone spacers maintain membrane integrity and biocompatibility even after radiation exposure.
- This finding has significant implications for reconstructive surgery in cancer patients.

