Leading Research Paper
Biomaterials
Characterization of interfacial reactions between connective tissue and allogenous implants used for subdermal soft tissue augmentation

https://doi.org/10.1016/j.ijom.2009.07.059Get rights and content

Abstract

The aim of this study was to investigate the molecular mechanisms underlying the problem of infection and pro-fibrotic tissue rearrangement around artificial devices used for soft tissue augmentation. An allogenous, acellularized dermal matrix (aADM) was implanted into subcutaneous pockets at the groin in 10 male Wistar rats. After 7 or 14 days, tissue specimens were obtained and analyzed for transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) by immunoblotting as well as α-smooth muscle actin (SMA)-and endoglin (CD105)-expression by immunohistochemistry. A TGFβ1-dependent α-SMA-overexpression as well as capillary lumina area regression were observed in the peri-implant connective tissue. VEGF expression decreased over the entire investigation period and resulted in delayed neovascularization of the implant. In conclusion, these experiments demonstrate that co-delivery of anti-fibrotic and pro-angiogenic agents is highly desirable to improve the clinical success of artificial tissue substitutes.

Section snippets

Animals

10 male Wistar rats (Institute of Laboratory Animal Science, University of Jena) with a mean age of 3 + 1 months and mean weight of 300–400 g were used. During the study period the animals were kept alone in Makrolon type III cages (Techniplast, Varese, Italy) at a temperature of 22 ± 0.5 °C, 55% humidity and a 12 h light/dark cycle. They received a pelleted standard rodent diet (N° 1320, Altromin, Lage, Germany) and fresh water ad libitum. The study was approved by the Thuringian state office for

Qualitative results

A fibro-contractile rearrangement of the peri-implant connective tissue was detectable on day 7 post operation. The positively stained myofibroblasts were distributed homogenously in the peri-implant connective tissue. No qualitative differences were detectable between day 7 and 14 (Fig. 1).

CD105 staining detected small and large diameter vessels in the peri- implant tissue. Some of the vessels were not only structurally detectable, but also functional as proved by the presence of erythrocytes

Discussion

In the rat model of subcutaneous implantation, biointegrability of artificial tissue substitutes can be assessed by monitoring peri-implant tissue reactions and their influence on tissue as well as capillary ingrowth into the material30.

Following implantation, the expression of the profibrotic and proinflammatory cytokine TGFβ1 was elevated in the peri-implant connective tissue. TGFβ1 binds to TGFβ receptor II35, which forms complexes with TGFβ receptor I, resulting in an autophosphorylation

Competing interests

None declared.

Ethical approval

The animal experiments were approved by the local authorities.

Acknowledgements

The study was supported by the Interdisciplinary Center for Clinical Research at the University Hospital of the University of Jena (Project No. FK B 307-04004).

The authors thank Mrs. Moll and Thiele for technical assistance.

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