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01.02.2011 | Original Article

In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival

verfasst von: Eiichi A. Miyasaka, Shreya Raghavan, Robert R. Gilmont, Krittika Mittal, Sita Somara, Khalil N. Bitar, Daniel H. Teitelbaum

Erschienen in: Pediatric Surgery International | Ausgabe 2/2011

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Abstract

Purpose

Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality.

Methods

Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence.

Results

All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF.

Conclusion

All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.

Nelson R, Norton N, Cautley E et al (1995) Community-based prevalence of anal incontinence. JAMA 274:559–561CrossRefPubMed

Perry S, Shaw C, McGrother C et al (2002) Prevalence of faecal incontinence in adults aged 40 years or more living in the community. Gut 50:480–484CrossRefPubMed

Bharucha AE (2003) Fecal incontinence. Gastroenterology 124:1672–1685CrossRefPubMed

Tjandra JJ, Lim JF, Hiscock R et al (2004) Injectable silicone biomaterial for fecal incontinence caused by internal anal sphincter dysfunction is effective. Dis Colon Rectum 47:2138–2146CrossRefPubMed

Thornton MJ, Kennedy ML, Lubowski DZ et al (2004) Long-term follow-up of dynamic graciloplasty for faecal incontinence. Colorectal Dis 6:470–476CrossRefPubMed

Hashish M, Raghavan S, Somara S et al (2010) Surgical implantation of a bioengineered internal anal sphincter. J Pediatr Surg 45:52–58CrossRefPubMed

Somara S, Gilmont RR, Dennis RG et al (2009) Bioengineered internal anal sphincter derived from isolated human internal anal sphincter smooth muscle cells. Gastroenterology 137:53–61CrossRefPubMed

Ikada Y (2006) Challenges in tissue engineering. J R Soc Interface 3:589–601CrossRefPubMed

Marra KG, Defail AJ, Clavijo-Alvarez JA et al (2008) FGF-2 enhances vascularization for adipose tissue engineering. Plast Reconstr Surg 121:1153–1164CrossRefPubMed

10.

Mullane EM, Dong Z, Sedgley CM et al (2008) Effects of VEGF and FGF2 on the revascularization of severed human dental pulps. J Dent Res 87:1144–1148CrossRefPubMed

11.

Larsen M, Willems WF, Pelzer M et al (2010) Augmentation of surgical angiogenesis in vascularized bone allotransplants with host-derived a/v bundle implantation, fibroblast growth factor-2, and vascular endothelial growth factor administration. J Orthop Res 28:1015–1021PubMed

12.

Cooke JW, Sarment DP, Whitesman LA et al (2006) Effect of rhPDGF-BB delivery on mediators of periodontal wound repair. Tissue Eng 12:1441–1450CrossRefPubMed

13.

Lee KD, Yamataka A, Kato Y et al (2006) Basic fibroblast growth factor and granulocyte colony-stimulating factor enhance mucosal surface expansion after adult small bowel transplantation without vascular reconstruction in rats. J Pediatr Surg 41:737–741CrossRefPubMed

14.

Heldin CH, Westermark B (1999) Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79:1283–1316PubMed

15.

Stanzel RD, Lourenssen S, Nair DG et al (2010) Mitogenic factors promoting intestinal smooth muscle cell proliferation. Am J Physiol Cell Physiol 299(4):C805–C817CrossRefPubMed

16.

Raghavan S, Miyasaka EA, Hashish M et al (2010) Successful implantation of physiologically functional bioengineered mouse internal anal sphincter. Am J Physiol Gastrointest Liver Physiol 299:G430–G439CrossRefPubMed

17.

Steed DL (2006) Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg 117:143S–149S (discussion 150S–151S, 2006)CrossRefPubMed

18.

Millette E, Rauch BH, Defawe O et al (2005) Platelet-derived growth factor-BB-induced human smooth muscle cell proliferation depends on basic FGF release and FGFR-1 activation. Circ Res 96:172–179CrossRefPubMed

Titel: In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival
verfasst von: Eiichi A. Miyasaka
Shreya Raghavan
Robert R. Gilmont
Krittika Mittal
Sita Somara
Khalil N. Bitar
Daniel H. Teitelbaum
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Pediatric Surgery International / Ausgabe 2/2011
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-010-2786-z

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In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival