scholarly journals Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1794
Author(s):  
Nina Noskovicova ◽  
Boris Hinz ◽  
Pardis Pakshir
Keyword(s):  
Foreign Body ◽  
Foreign Body Reaction ◽  
Scar Tissue ◽  
Surgical Removal ◽  
Implant Surface ◽  
Implantable Medical Devices ◽  
Implant Materials ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Clinical Complications

Body implants and implantable medical devices have dramatically improved and prolonged the life of countless patients. However, our body repair mechanisms have evolved to isolate, reject, or destroy any object that is recognized as foreign to the organism and inevitably mounts a foreign body reaction (FBR). Depending on its severity and chronicity, the FBR can impair implant performance or create severe clinical complications that will require surgical removal and/or replacement of the faulty device. The number of review articles discussing the FBR seems to be proportional to the number of different implant materials and clinical applications and one wonders, what else is there to tell? We will here take the position of a fibrosis researcher (which, coincidentally, we are) to elaborate similarities and differences between the FBR, normal wound healing, and chronic healing conditions that result in the development of peri-implant fibrosis. After giving credit to macrophages in the inflammatory phase of the FBR, we will mainly focus on the activation of fibroblastic cells into matrix-producing and highly contractile myofibroblasts. While fibrosis has been discussed to be a consequence of the disturbed and chronic inflammatory milieu in the FBR, direct activation of myofibroblasts at the implant surface is less commonly considered. Thus, we will provide a perspective how physical properties of the implant surface control myofibroblast actions and accumulation of stiff scar tissue. Because formation of scar tissue at the surface and around implant materials is a major reason for device failure and extraction surgeries, providing implant surfaces with myofibroblast-suppressing features is a first step to enhance implant acceptance and functional lifetime. Alternative therapeutic targets are elements of the myofibroblast mechanotransduction and contractile machinery and we will end with a brief overview on such targets that are considered for the treatment of other organ fibroses.

scholarly journals Mechanical matching of implant to host minimises foreign body reaction

2019 ◽  
Author(s):  
Alejandro Carnicer-Lombarte ◽  
Damiano G. Barone ◽  
Ivan B. Dimov ◽  
Russell S. Hamilton ◽  
Malwina Prater ◽  
...  
Keyword(s):  
Foreign Body ◽  
Foreign Body Reaction ◽  
Scar Tissue ◽  
Host Tissue ◽  
Medical Implants ◽  
Implant Surface ◽  
Biomedical Implant ◽  
Manufacturing Techniques ◽  
Implant Coatings

AbstractMedical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1–4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness found in healthy tissue. Coating implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus of ∼1 kPa or below led to significantly reduced levels of inflammation and fibrosis after chronic implantation both in peripheral nerves and subcutaneously. This effect was linked to the nuclear localisation of the mechanosensitive transcriptional regulator YAP in vivo. Hence, we identify the mechanical mismatch between implant and tissue as a driver of FBR. Soft implant coatings matching the mechanical properties of host tissue minimized FBR and may be used as a novel therapeutic strategy to improve long-term biomedical implant stability without extensive modification of current implant manufacturing techniques, thus facilitating clinical translation.One sentence summaryForeign body reaction to medical implants can be avoided by matching the stiffness of the implant surface to that of the host tissue.

scholarly journals Biomedical and Tissue Engineering Strategies to Control Foreign Body Reaction to Invasive Neural Electrodes

2021 ◽  
Vol 9 ◽  
Author(s):  
Manuele Gori ◽  
Gianluca Vadalà ◽  
Sara Maria Giannitelli ◽  
Vincenzo Denaro ◽  
Giovanni Di Pino
Keyword(s):  
Tissue Engineering ◽  
Foreign Body ◽  
Foreign Body Reaction ◽  
The Body ◽  
Neural Interfaces ◽  
Host Immune System ◽  
Neural Implants ◽  
Inflammatory Phase ◽  
Inflammatory State ◽  
And Performance

Neural-interfaced prostheses aim to restore sensorimotor limb functions in amputees. They rely on bidirectional neural interfaces, which represent the communication bridge between nervous system and neuroprosthetic device by controlling its movements and evoking sensory feedback. Compared to extraneural electrodes (i.e., epineural and perineural implants), intraneural electrodes, implanted within peripheral nerves, have higher selectivity and specificity of neural signal recording and nerve stimulation. However, being implanted in the nerve, their main limitation is represented by the significant inflammatory response that the body mounts around the probe, known as Foreign Body Reaction (FBR), which may hinder their rapid clinical translation. Furthermore, the mechanical mismatch between the consistency of the device and the surrounding neural tissue may contribute to exacerbate the inflammatory state. The FBR is a non-specific reaction of the host immune system to a foreign material. It is characterized by an early inflammatory phase eventually leading to the formation of a fibrotic capsule around intraneural interfaces, which increases the electrical impedance over time and reduces the chronic interface biocompatibility and functionality. Thus, the future in the reduction and control of the FBR relies on innovative biomedical strategies for the fabrication of next-generation neural interfaces, such as the development of more suitable designs of the device with smaller size, appropriate stiffness and novel conductive and biomimetic coatings for improving their long-term stability and performance. Here, we present and critically discuss the latest biomedical approaches from material chemistry and tissue engineering for controlling and mitigating the FBR in chronic neural implants.

scholarly journals Reduction of epidural fibrosis after laminectomy in rabbits by omental free graft

2013 ◽  
Vol 58 (No. 1) ◽  
pp. 25-31 ◽  
Author(s):  
N. Brkljaca Bottegaro ◽  
J. Kos ◽  
B. Pirkic ◽  
O. Smolec ◽  
Z. Grabarevic ◽  
...  
Keyword(s):  
Foreign Body ◽  
Dura Mater ◽  
Foreign Body Reaction ◽  
Fibrous Tissue ◽  
Scar Tissue ◽  
Control Group ◽  
Epidural Fibrosis ◽  
Free Graft ◽  
Increased Risk ◽  
Experimental Group

Epidural fibrosis is an extradural scar tissue formed after a laminectomy procedure. It is associated with persistent pain after spinal surgery and an increased risk of complications during revision surgery. The aim of this study was to determine the preventive effects of local application of an omental free graft in minimising spinal epidural fibrosis in a rabbit laminectomy model. Twenty two rabbits were randomly divided in two groups, a control group of seven and an experimental group of 15 animals. A dorsal laminectomy at levels L<sub>1</sub> to L<sub>3 </sub>was performed on each rabbit of both groups. Prior to the laminectomy procedure, the animals from the experimental group were submitted to a laparotomy in order to obtain the free omental graft. The graft was then applied to the same animal at the dural deffect. All rabbits were euthanised six weeks after surgery and spine segments L<sub>1</sub> to L<sub>3</sub> were removed. Histological sections were evaluated for fibrosis intensity at the laminectomy level, the adhesion degree between dura mater and fibrous tissue and the presence of the foreign body reaction. A statistically significant correlation was established for the foreign body reaction presence and belonging to the group, which can be explained by the omental effects on inflammation reduction and healing promotion. The degree of adhesion between the dura mater and fibrous tissue and the intensity of the fibrous tissue at the laminectomy level were lower in the experimental group although the differences were not statistically significant. The use of free omental grafts is thus a promising technique in epidural fibrosis prevention.

scholarly journals The Potential Role of Polymethyl Methacrylate as a New Packaging Material for the Implantable Medical Device in the Bladder

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Su Jin Kim ◽  
Bumkyoo Choi ◽  
Kang Sup Kim ◽  
Woong Jin Bae ◽  
Sung Hoo Hong ◽  
...  
Keyword(s):  
Foreign Body ◽  
Polymethyl Methacrylate ◽  
Inflammatory Cytokines ◽  
Medical Devices ◽  
Foreign Body Reaction ◽  
Early Period ◽  
Implantable Medical Device ◽  
Implantable Medical Devices ◽  
Macrophage Activity ◽  
Implanted Medical Devices

Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-αwere observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder.

scholarly journals Fibrin Polymer on the Surface of Biomaterial Implants Drives the Foreign Body Reaction

2021 ◽  
Author(s):  
Arnat Balabiyev ◽  
Nataly P. Podolnikova ◽  
Jacquelyn A. Kilbourne ◽  
D. Page Baluch ◽  
David Lowry ◽  
...  
Keyword(s):  
Foreign Body ◽  
Foreign Body Reaction ◽  
Giant Cells ◽  
The Body ◽  
Fibrous Capsule ◽  
Host Proteins ◽  
Implant Surface ◽  
Foreign Body Giant Cells ◽  
Biological Substrate

ABSTRACTImplantation of biomaterials and medical devices in the body triggers the foreign body reaction (FBR) which is characterized by macrophage fusion at the implant surface leading to the formation of foreign body giant cells and the development of the fibrous capsule enveloping the implant. While adhesion of macrophages to the surface is an essential step in macrophage fusion and implanted biomaterials are known to rapidly acquire a layer of host proteins, a biological substrate that is responsible for this process in vivo is unknown. Here we show that mice with genetically-imposed fibrinogen deficiency display a dramatic reduction of macrophage fusion on implanted biomaterials and are protected from the formation of fibrin-containing granulation tissue, a precursor of the fibrous capsule. Furthermore, macrophage fusion on biomaterials implanted in FibAEK mice that express a mutated form of fibrinogen incapable of thrombin-mediated polymerization was strongly reduced. Surprisingly, despite the lack of fibrin, the capsule was formed in FibAEK mice, although it had a different composition and distinct mechanical properties than that in wild-type mice. Specifically, while mononuclear α-SMA-expressing macrophages embedded in the capsule of both strains of mice secreted collagen, the amount of collagen and its density in the tissue of FibAEK mice was reduced. These data identify fibrin polymer as a key biological substrate driving the development of the FBR.

scholarly journals Improvement of biohistological response of facial implant materials by tantalum surface treatment

2019 ◽  
Vol 41 (1) ◽  
Author(s):  
Mohammed Mousa Bakri ◽  
Sung Ho Lee ◽  
Jong Ho Lee
Keyword(s):  
Foreign Body ◽  
Soft Tissue ◽  
Surface Treatment ◽  
Clinical Applications ◽  
Tissue Response ◽  
Bone Surface ◽  
Tissue Thickness ◽  
Implant Materials ◽  
Soft Tissue Thickness

Abstract Background A compact passive oxide layer can grow on tantalum (Ta). It has been reported that this oxide layer can facilitate bone ingrowth in vivo though the development of bone-like apatite, which promotes hard and soft tissue adhesion. Thus, Ta surface treatment on facial implant materials may improve the tissue response, which could result in less fibrotic encapsulation and make the implant more stable on the bone surface. The purposes of this study were to verify whether surface treatment of facial implant materials using Ta can improve the biohistobiological response and to determine the possibility of potential clinical applications. Methods Two different and commonly used implant materials, silicone and expanded polytetrafluoroethylene (ePTFE), were treated via Ta ion implantation using a Ta sputtering gun. Ta-treated samples were compared with untreated samples using in vitro and in vivo evaluations. Osteoblast (MG-63) and fibroblast (NIH3T3) cell viability with the Ta-treated implant material was assessed, and the tissue response was observed by placing the implants over the rat calvarium (n = 48) for two different lengths of time. Foreign body and inflammatory reactions were observed, and soft tissue thickness between the calvarium and the implant as well as the bone response was measured. Results The treatment of facial implant materials using Ta showed a tendency toward increased fibroblast and osteoblast viability, although this result was not statistically significant. During the in vivo study, both Ta-treated and untreated implants showed similar foreign body reactions. However, the Ta-treated implant materials (silicone and ePTFE) showed a tendency toward better histological features: lower soft tissue thickness between the implant and the underlying calvarium as well as an increase in new bone activity. Conclusion Ta surface treatment using ion implantation on silicone and ePTFE facial implant materials showed the possibility of reducing soft tissue intervention between the calvarium and the implant to make the implant more stable on the bone surface. Although no statistically significant improvement was observed, Ta treatment revealed a tendency toward an improved biohistological response of silicone and ePTFE facial implants. Conclusively, tantalum treatment is beneficial and has the potential for clinical applications.

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