In vivo biodegradability and biocompatibility evaluation of novel alanine ester based polyphosphazenes in a rat model

Swaminathan Sethuraman, Lakshmi S. Nair, Saadiq El-Amin, Robert Farrar, My Tien N. Nguyen, Anurima Singh, Harry R. Allcock, Yaser E. Greish, Paul W. Brown, Cato T. Laurencin

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Abstract

Amino acid ester substituted polyphosphazenes are attractive candidates for various biomedical applications because of their biocompatibiliry, controllable hydrolytic degradation rates, and nontoxic degradation products. In this study, the biocompatibiliry of three L-alanine ethyl ester functionalized polyphosphazenes was evaluated in a subcutaneous rat model. The polymers used in the study were poly[bis(ethylalanato)phos-phazene] (PNEA), poly[(50% ethylalanato) (50% methylphenoxy) phosphazene] (PNEA50mPh 50), and poly[(50% ethylalanato)(50% phenyl phenoxy) phosphazene] (PNEA50PhPh50). Polymer disks of diameter 7.5 mm were prepared by a solvent evaporation technique and were implanted subcutaneously in rats. After 2, 4, and 12 weeks, the polymer along with the surrounding tissues were excised, prepared, and viewed by light microscopy to evaluate the tissue responses of the implanted polymers. The tissue responses were classified as minimal, mild, or moderate, based on a biocompatibiliry scheme developed in our laboratory. Minimal inflammation was characterized by the presence of few neutrophils, erythrocytes, and lymphocytes; mild response was characterized by the predominant presence of macrophages, fibroblasts, or giant cells; and moderate inflammation was characterized by the abundance of macrophages, giant cells, and by the presence of tissue exudates. The in vivo degradation profiles of the polymers at various time points were evaluated by gel permeation chromatography (GPC). PNEA and PNEA50mPh50 matrices elicited varying levels of tissue responses during the 12-week implantation period. At 2 weeks both polymers evoked a moderate response, and by 12 weeks the response was found to be mild. However, PNEA50PhPh50 elicited a mild response at the end of 2 weeks and demonstrated a further decreased inflammatory response after12 weeks. The in vivo degradation of the polymers was followed by determining the molecular weights of the explanted polymer disks. PNEA and PNEA50mPh50 disks showed significant decrease in molecular weight after 2 weeks of implantation. The molecular weights of PNEA and PNEA50mPh50 residues could not be determined by GPC after 12 weeks of implantation because of almost complete degradation. On the other hand the in vivo degradation of PNEA 50PhPh50 was found to be slow, with a 63% loss in molecular weight in 12 weeks. Furthermore, this polymer maintained its shape and structure during the entire study. Thus, these polymers demonstrated excellent tissue compatibility and in vivo biodegradability and can be potential candidates for various biomedical applications.

Original languageEnglish (US)
Pages (from-to)679-687
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume77
Issue number4
DOIs
StatePublished - Jun 15 2006

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All Science Journal Classification (ASJC) codes

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

Cite this

Sethuraman, S., Nair, L. S., El-Amin, S., Farrar, R., Nguyen, M. T. N., Singh, A., Allcock, H. R., Greish, Y. E., Brown, P. W., & Laurencin, C. T. (2006). In vivo biodegradability and biocompatibility evaluation of novel alanine ester based polyphosphazenes in a rat model. Journal of Biomedical Materials Research - Part A, 77(4), 679-687. https://doi.org/10.1002/jbm.a.30620