Porcine Dermis-Derived Collagen Membranes Induce Implantation Bed Vascularization Via Multinucleated Giant Cells: A Physiological Reaction?

Abstract

In this study, the tissue reactions to 2 new porcine dermis-derived collagen membranes of different thickness were analyzed. The thicker material (Mucoderm) contained sporadically preexisting vessel skeletons and fatty islands. The thinner membrane (Collprotect) had a bilayered structure (porous and occlusive side) without any preexisting structures. These materials were implanted subcutaneously in mice to analyze the tissue reactions and potential transmembranous vascularization. Histological and histomorphometrical methodologies were performed at 4 time points (3, 10, 15, and 30 days). Both materials permitted stepwise connective tissue ingrowth into their central regions. In the Mucoderm matrix, newly built microvessels were found within the preexisting vessel and fatty island skeletons after 30 days. This vascularization was independent of the inflammation-related vascularization on both material surfaces. The Collprotect membrane underwent material disintegration by connective tissue strands in combination with vessels and multinucleated giant cells. The histomorphometric analyses revealed that the thickness of Mucoderm did not decrease significantly, while an initial significant decrease of membrane thickness in the case of Collprotect was found at day 15. The present results demonstrate that the 2 analyzed collagen membranes underwent a multinucleated giant cell-associated vascularization. Neither of the materials underwent transmembraneous vascularization. The microvessels were found within the preexisting vessel and fatty island skeletons. Additional long-term studies and clinical studies are necessary to determine how the observed foreign body giant cells affect tissue regeneration.

Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells—New insights into the material‐mediated healing process

“…In the past few decades it has been repeatedly shown that multinucleated giant cells (MNGCs) are involved in the tissue reaction to numerous biomaterials, including the majority of bone substitutes . Based on the knowledge gained from autologous bone grafts it has manifoldly been supposed that these MNGCs are osteoclasts or so‐called “osteoclast‐like cells” and appear to be involved in the processes of “physiological” bone turnover during defect repair .…”

“… Furthermore, numerous studies have shown that TRAP‐expressing MNGCs also become induced after the implantation of bone substitutes as well as different other classes of biomaterials in ectopic tissues and not only within the microenvironment of bone tissue (Fig. ) .…”

“…In the past few decades it has been repeatedly shown that multinucleated giant cells (MNGCs) are involved in the tissue reaction to numerous biomaterials, including the majority of bone substitutes. [1][2][3][4][5][6][7][8][9][10][11][12][13] Based on the knowledge gained from autologous bone grafts it has manifoldly been supposed that these MNGCs are osteoclasts or so-called "osteoclast-like cells" and appear to be involved in the processes of "physiological" bone turnover during defect repair. [14][15][16][17][18] Four indications have led to this assumption: (1) The chemical similarity of most bone substitutes to the calcified bone matrix, that is calcium phosphate (CaP)-based materials, as their substrates; (2) their multinucleation; (3) their expression of tartrate-resistant acid phosphatase (TRAP), a marker molecule for osteoclasts and bone turnover; and (4) their ability to degrade the CaP content of the different classes of bone substitutes.…”

“…1). [1][2][3][4][6][7][8]13,27 232 In addition, it has been demonstrated that the expression of the TRAP enzyme is not a specific indication for osteoclasts as two different subforms of this molecule have been identified. 33,34 In this context, it has also been shown that the TRAP5b subform is specific for osteoclasts, while the TRAP5a subform is correlated with inflammatory reactions to different stimuli and is also expressed by a variety of cell types.…”

Heterogeneity of biomaterial‐induced multinucleated giant cells: Possible importance for the regeneration process?

“…Additionally, a third cell type, the “biomaterial‐associated multinucleated giant cell” (BMGC), has been shown to be involved in the tissue reactions to a variety of biomaterials with different physicochemical properties . Interestingly, this multinucleated cell type has been found to be involved in the tissue reactions to both synthetic biomaterials, such as calcium phosphate‐based bone substitutes, and PFTE‐based barrier materials, as well as to “natural” biomaterials, such as collagen membranes or xenogeneic bone substitutes based on their natural (micro‐ or nano‐) structure . It has been shown that their formation, which is based on the fusion of mononuclear cells, such as monocytes and macrophages, is related to the physicochemical characteristics of a biomaterial .…”