The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

Rolfe, Barbara E.; Mooney, Jane; Zhang, Bing; Jahnke, Sani; Le, Sarah-Jane; Chau, Yu-Qian; Huang, Qiping; Wang, Hao; Campbell, Gordon; Campbell, Julie H.

doi:10.5772/21790

Cited by 45 publications

(53 citation statements)

References 127 publications

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“…35,53,56 Although, increased porosity may be beneficial as this tends to correlate with increased vascularity. 44,48 It’s also possible that a patient’s local and systemic inflammatory status may significantly affect bone outcomes as IL6 was elevated in the micro-roughed groups and lead to fewer unions. There are very many possible avenues for future research on the Masquelet Technique that are directly translatable to clinical application.…”

Section: Discussionmentioning

confidence: 99%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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We and others have shown that changing surface characteristics of the spacer implanted during the first Masquelet stage alters some aspects of membrane development. Previously we demonstrated that titanium spacers create membranes that are better barriers to movement of solutes >70kDa in size than polymethyl methacrylate (PMMA) induced-membranes, and roughening creates more mechanically compliant membranes. However, it is unclear if these alterations affect the membrane’s biochemical environment or bone regeneration during the second stage. Ten-week-old, male Sprague-Dawley rats underwent an initial surgery to create an externally stabilized 6mm femoral defect. PMMA or titanium spacers with smooth (~1um) or roughened (~8um) surfaces were implanted. Four weeks later, rats were either euthanized for membrane harvest or underwent the second Masquelet surgery. Titanium spacers induced thicker membranes that were similar in structure and biochemical expression. All membranes were bilayered with the inner layer having increased factor expression (BMP2, TGFβ, IL6, and VEGF). Roughening increased overall IL6 levels. Ten-weeks post-engraftment, PMMA-smooth induced membranes better supported bone regeneration (60% union). The other groups only had 1 or 2 that united (9–22%). There were no significant differences in any microCT or dynamic histology outcome. In conclusion, this study suggests that the membrane’s important function in the Masquelet technique is not simply as a barrier. There is likely a critical biochemical, cellular, or vascular component as well.

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Section: Discussionmentioning

confidence: 99%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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“…Transforming growth factor beta (TGF-β) is one of the main factors responsible for promoting fibroblast proliferation and subsequent collagen deposition by these cells during wound healing (28), and is produced by different cell types including macrophages and epithelial cells (46). Aprotinin has been shown to completely inhibit the activation of TGF-β, and therefore reduce tissue fibrosis and capsule formation in vivo (46, 47). Therefore, a potential explanation for the reduced fibrous capsule thickness observed surrounding our aprotinin implants is the interaction of aprotinin with TGF-β activation via this pathway, resulting in decreased collagen deposition by fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Proangiogenic microtemplated fibrin scaffolds containing aprotinin promote improved wound healing responses

et al. 2013

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Survival of tissue engineered constructs after implantation depends heavily on induction of a vascular response in host tissue, promoting a quick anastomosis of the cellular graft. Additionally, implanted constructs typically induce fibrous capsule formation, effectively preventing graft integration with host tissue. Previously we described the development of a high density microtemplated fibrin scaffold for cardiac tissue engineering applications with tunable degradation and mechanical properties which promoted seeded cell survival and organization in vitro (1). Scaffold degradation in vitro was controllable by addition of the serine protease inhibitor aprotinin and/or the fibrin cross-linker Factor XIII (FXIII). The goal of this study was to assess host tissue responses to these fibrin scaffold formulations by determining effects on scaffold degradation, angiogenic responses, and fibrous capsule formation in a subcutaneous implant model. Aprotinin significantly decreased scaffold degradation over 2 weeks of implantation. A significant increase in capillary infiltration of aprotinin implants was found after 1 and 2 weeks, with a significantly greater amount of capillaries reaching the interior of aprotinin scaffolds. Interestingly, after 2 weeks the aprotinin scaffolds had a significantly thinner, yet apparently more cellular fibrous capsule than unmodified scaffolds. These results indicate aprotinin not only inhibits fibrin scaffold degradation, but also induces significant responses in the host tissue. These included an angiogenic response resulting in increased vascularization of the scaffold material over a relatively short period of time. In addition, aprotinin release from scaffolds may reduce fibrous capsule formation, which could help promote improved integration of cell-seeded scaffolds with host tissue.

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“…In addition to their role in diseases like cystic fibrosis, NETs have also been shown to accumulate on sterile implant materials . Such fibrosis‐triggering cell products can initiate an impaired efficiency of the implant or even device failure . One possibility for reducing the adhesion of neutrophils and subsequent NET production on implants is to coat the implant surfaces with mucins .…”

Section: Introductionmentioning

confidence: 99%

In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones

Galuska

Tharmalingam

et al. 2017

The FEBS Journal

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Neutrophil extracellular traps (NET) are formed against pathogens. However, various diseases are directly linked to this meshwork of DNA. The cytotoxic properties of extracellular histones especially seem to be an important trigger during these diseases. Furthermore, NET accumulation on implants is discussed to result in an impaired efficiency or failure, depending on the category of implant. Interestingly, mucins have been investigated as surface coatings potentially capable of reducing neutrophil adhesion. Similarly, polysialic acid was shown to inactivate the cytotoxic properties of extracellular histones. We wanted to combine the probability to decrease the adhesion of neutrophils using mucins with the capability of sialic acid polymers to counteract histone-mediated cytotoxicity. To this end, we elongate cervical mucins using bacterial polysialyltransferases. Subsequent cell-based experiments demonstrated the activity of elongated mucins against histone-mediated cytotoxicity. Thus, polysialylated mucins may represent a novel component to coat implants or to combat diseases with exaggerated NET formation.

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The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

Cited by 45 publications

References 127 publications

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Proangiogenic microtemplated fibrin scaffolds containing aprotinin promote improved wound healing responses

In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones

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