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 ◽  
...  

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.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiaxi Chen ◽  
Huiqun Zhou ◽  
Daping Xie ◽  
Yiming Niu

Abstract Background Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants. Methods First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials. Results Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure. Conclusions Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1794
Author(s):  
Nina Noskovicova ◽  
Boris Hinz ◽  
Pardis Pakshir

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.


2021 ◽  
Author(s):  
Jiaxi Chen ◽  
Huiqun Zhou ◽  
Daping Xie ◽  
Yiming Niu

Abstract BackgroundImplantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implant. The level of foreign-body reaction can be modulated by material properties.MethodsFirst, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and rheology were measured to characterize the material properties of cryogels. Live/dead staining of cells and CCK-8 was performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for in vitro tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials.ResultsOur data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels show well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure.ConclusionsCollectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body response and promote the performance of medical devices.


2021 ◽  
Author(s):  
Arnat Balabiyev ◽  
Nataly P. Podolnikova ◽  
Jacquelyn A. Kilbourne ◽  
D. Page Baluch ◽  
David Lowry ◽  
...  

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.


Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 275
Author(s):  
Shan Yasin Mian ◽  
Jonathan Roy Honey ◽  
Alejandro Carnicer-Lombarte ◽  
Damiano Giuseppe Barone

Brain–computer interfaces (BCI) are reliant on the interface between electrodes and neurons to function. The foreign body reaction (FBR) that occurs in response to electrodes in the brain alters this interface and may pollute detected signals, ultimately impeding BCI function. The size of the FBR is influenced by several key factors explored in this review; namely, (a) the size of the animal tested, (b) anatomical location of the BCI, (c) the electrode morphology and coating, (d) the mechanics of electrode insertion, and (e) pharmacological modification (e.g., drug eluting electrodes). Trialing methods to reduce FBR in vivo, particularly in large models, is important to enable further translation in humans, and we systematically reviewed the literature to this effect. The OVID, MEDLINE, EMBASE, SCOPUS and Scholar databases were searched. Compiled results were analysed qualitatively. Out of 8388 yielded articles, 13 were included for analysis, with most excluded studies experimenting on murine models. Cats, rabbits, and a variety of breeds of minipig/marmoset were trialed. On average, over 30% reduction in inflammatory cells of FBR on post mortem histology was noted across intervention groups. Similar strategies to those used in rodent models, including tip modification and flexible and sinusoidal electrode configurations, all produced good effects in histology; however, a notable absence of trials examining the effect on BCI end-function was noted. Future studies should assess whether the reduction in FBR correlates to an improvement in the functional effect of the intended BCI.


2007 ◽  
Vol 330-332 ◽  
pp. 193-196
Author(s):  
Duck Hyun Kim ◽  
Kang Sik Lee ◽  
Jung Hwa Kim ◽  
Jae Suk Chang ◽  
Yung Tae Kim

We observed the cytotoxicity of human bone marrow stromal cells(hBMSCs) by microparticles of bioactive glass with four particle groups(same chemical composition-45S5 but produced by two different manufacturer and two different size groups). In vivo test using rat calvaria were also carried out. The apoptosis rates of all small particle groups(10-20 ㎛) were increased than large(500-700 ㎛ or 200-900 ㎛) particle groups in any culture time and any amount of particles with statistical significance. In vivo study we observed pathologic signs such as macrophages and foreign-body giant cells in rat calvaria by micro-particles of bioglass. Small(10- 20 ㎛) sized particles induced foreign body reaction and bone resorption. There was proliferation of macrophages and cells in large number. But in large particle groups, only fibroblasts were surrounding the particles. The micro-particles of bioglass induced apoptosis of hBMSC and foreign body reaction in calvaria of rat, therefore micro-particles of bioglass may cause osteolysis if used in replacement arthroplasty.


1998 ◽  
Vol 45 (7) ◽  
pp. 921-927 ◽  
Author(s):  
H.H. Qiu ◽  
L.W. Hedlund ◽  
M.R. Neuman ◽  
C.R. Edwards ◽  
R.D. Black ◽  
...  

1988 ◽  
Vol 7 (4) ◽  
pp. 469-479 ◽  
Author(s):  
James M. Anderson

The goal of in vivo testing of a medical device is to determine the safety or biocompatibility of the device in a biological environment. Biocompatibility is the ability of a medical device to perform with an appropriate host response in a specific application. Biocompatibility assessment is considered to be a measure of the magnitude and duration of adverse alterations in homeostatic mechanisms that determine the host response. Perspectives are provided on the role of injury, tissue responses to medical devices, and blood responses to medical devices. The concept of the normal foreign body reaction is presented. The potential importance of the macrophage, an important component of the foreign body reaction, in controlling the biocompatibility in the in vivo environment is discussed.


2021 ◽  
Author(s):  
Yixin Zhang ◽  
Hanwen Liang ◽  
Qian Luo ◽  
Jianlin Chen ◽  
Nan Zhao ◽  
...  

Abstract Biodegradable polymer particles have been used as dermal fillers for pre-clinical and clinical trials. The impact of material properties of polymers is very important to develop products for aesthetic medicine such as dermal fillers. Herein, eight biodegradable polymers with different molecular weights, chemical compositions or hydrophilic-hydrophobic properties were prepared and characterized for systematical study for aesthetic medicine applications. Polymer microspheres with 20-100 nm were prepared. The in vitro degradation study showed that poly (L-lactic-co-glycolic acid) 75/25 (PLLGA75/25) microspheres degraded the fastest while PLLA microspheres with intrinsic viscosity of 6.89 ([η]=6.89) with the highest molecular weight showed the slowest degradation rate. After these microspheres were fabricated dermal fillers according to the formula of Sculptra®, they were injected subcutaneously into the back skin of rabbits. In vivo results demonstrated that the degradation rate of microspheres strongly correlated with the foreign body reaction and collagen regeneration was induced by microspheres. The microspheres with faster degradation rate induced inflammatory response and the collagen regeneration maintained in shorter time. PLLA ([η]=3.80) microsphere with a moderate molecular weight and degradation rate could strongly regenerate type I and III collagen to maintain a long-term aesthetic medicine effect. These properties of size, morphology and degradation behavior would influence the foreign body reaction and collagen regeneration.


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