The Use of Integra Flowable Matrix As a Soft Tissue Filler

Background:  The search for an effective, biocompatible, and nonimmunogenic filler for soft tissue loss has been an ongoing effort. Integra Flowable Matrix has been demonstrated to improve wound healing in irregular-shaped wound beds and tunneling wounds. However, it has not been investigated for potential as a long-term filler. The matrix is a gel-like mixture of collagen and chondroitin sulphate matrix, which may lead to better volumetric and cellular infiltration than traditional fillers. This study’s aim was therefore to assess volume retention over time, cellular infiltration into the matrix, and immunogenic properties of the material in a small animal model.

Methods: This study included a total of 40 SKH1-elite, hairless mice. All mice underwent injection of 1mL of Integra Flowable Matrix in the subdermal region of the scalp. Micro-CT was performed on 10 randomly selected mice at time 0, 2 weeks, and 8 weeks. CTs were 3D reconstructed and volume assessed of the implanted graft. 20 mice were euthanized at 2 weeks and 20 at 8 weeks. Volume of the grafts were assessed at this point using volume displacement. Grafts also went histological analysis with hematoxylin-eosin staining and immunohistochemistry to assess cell type infiltration into the matrix. Electron microscopy was also performed to assess cellular infiltration on a microscopic level into the material.

Results: Integra Flowable Matrix was tolerated well by all mice as a filler. Average volume retention, measured by volume displacement, was 72.9% at 2 weeks and 47.9% at 8 weeks. This correlated well with volume measured by micro-CT analysis of 10 randomly selected mice. Vasculature entering the matrix was observed macroscopically at both 2 weeks and 8 weeks. Electron microscopy demonstrated cellular infiltration into the matrix as well as encapsulation of the material. Immunohistochemistry showed infiltration of fibroblast cells as well as increased vascularization in the matrix without evidence of immunogenic cell infiltration of T cells or macrophages.

Discussion: This study demonstrates the potential to use Integra Flowable Matrix as a soft tissue filler for reconstructive patients or aesthetic patients requiring soft tissue volume. Volume retention over time was comparable to current soft tissue fillers on the market, and higher than autologous fat grafting. Electron microscopy and immunohistochemistry data demonstrate vascularization of the matrix and infiltration of fibroblasts and mesenchymal stem cells. Future research combining Flowable Matrix with autologous stem cells and adipose cells may also be promising.