Bletilla striata polysaccharide cryogel scaffold for spatial control of foreign-body reaction

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.

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Bletilla striata Polysaccharide Cryogel Scaffold for Spatial Control of Foreign-body Reaction

10.21203/rs.3.rs-999929/v1 ◽

2021 ◽

Author(s):

Jiaxi Chen ◽

Huiqun Zhou ◽

Daping Xie ◽

Yiming Niu

Keyword(s):

Foreign Body ◽

Pore Size ◽

Foreign Body Reaction ◽

Foreign Body Response ◽

Host Tissue ◽

Bletilla Striata ◽

Pore Sizes ◽

Tissue Integration

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.

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Large Animal Studies to Reduce the Foreign Body Reaction in Brain–Computer Interfaces: A Systematic Review

Biosensors ◽

10.3390/bios11080275 ◽

2021 ◽

Vol 11 (8) ◽

pp. 275

Author(s):

Shan Yasin Mian ◽

Jonathan Roy Honey ◽

Alejandro Carnicer-Lombarte ◽

Damiano Giuseppe Barone

Keyword(s):

Foreign Body ◽

Animal Studies ◽

Foreign Body Reaction ◽

Inflammatory Cells ◽

Anatomical Location ◽

Large Animal ◽

Brain Computer Interfaces ◽

Computer Interfaces ◽

Electrode Insertion

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.

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Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles

RSC Advances ◽

10.1039/c8ra03914c ◽

2018 ◽

Vol 8 (43) ◽

pp. 24633-24640 ◽

Cited By ~ 14

Author(s):

Jie Li ◽

Suqin Shen ◽

Fei Kong ◽

Ting Jiang ◽

Cui Tang ◽

...

Keyword(s):

Mesoporous Silica ◽

Pore Size ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Pore Sizes

MSN with suitable pore sizes achieved an outstanding performance for in vitro and in vivo antitumor efficacies.

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Mechanical matching of implant to host minimises foreign body reaction

10.1101/829648 ◽

2019 ◽

Cited By ~ 3

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.

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Local Foreign-Body Reaction to Commercial Biodegradable Implants: An in Vivo Animal Study

Craniomaxillofacial Trauma & Reconstruction ◽

10.1055/s-0033-1364199 ◽

2014 ◽

Vol 7 (1) ◽

pp. 27-33 ◽

Cited By ~ 26

Author(s):

Amy S. Xue ◽

John C. Koshy ◽

William M. Weathers ◽

Erik M. Wolfswinkel ◽

Yoav Kaufman ◽

...

Keyword(s):

Foreign Body ◽

Foreign Body Reaction ◽

Close Association ◽

Inflammatory Cells ◽

Giant Cells ◽

Inflammatory Reactions ◽

Debris Accumulation ◽

Foreign Body Reactions ◽

The 1960S

Biodegradable plates have been used extensively in fracture fixation since the 1960s. They rarely cause stress-protection atrophy or problems requiring secondary plate removal, common complications seen with metallic plates. However, aseptic foreign-body reactions have been reported, sometimes years after the original implantation. Both inadequate polymer degradation and debris accumulation have been implicated as causes. The current generation of commercial biodegradable plates is formulated to minimize this complication by altering the ratio of polylactic and polyglycolic acids. This in vivo study compares the degree of local foreign-body reaction of two commercially available resorbable plates in rabbits. Two types of biodegradable plates were examined: poly(D/L)lactide acid (PDLLA) and polylactide-co-glycolide acid (PLGA). Each plate was placed into a periosteal pericalvarial pocket created beneath the anterior or posterior scalp of a rabbit. Humane killing occurred at 3, 6, and 12 months postoperatively. Foreign-body reaction was evaluated histologically. The PDLLA plates demonstrated marked local foreign-body reactions within the implant capsule as early as 3 months after implantation, with presence of inflammatory cells and granulomatous giant cells in close association with the implant material. All local foreign-body reactions were subclinical with no corresponding tissue swelling requiring drainage. PLGA plates did not demonstrate any signs of inflammatory reactions. In addition, the PLGA plates did not appear to resorb or integrate at 12 months. Neither PDLLA nor PLGA plates demonstrated inflammation of the soft tissue or adjacent bone outside the implant capsule. In our study, the PDLLA plates demonstrated histological evidence of foreign-body reaction that is confined within the implant capsule, which was not seen with the PLGA plates. This finding may be attributable to the lack of significant resorption seen in the PLGA plates. Both PDLLA and PLGA plates were biocompatible with the rabbit tissue environment and should be considered for continued use in craniofacial, maxillofacial, and orthopedic reconstruction.

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Extent of Inflammation and Foreign Body Reaction to Porous Polyethylene In Vitro and In Vivo

In Vivo ◽

10.21873/invivo.11479 ◽

2019 ◽

Vol 33 (2) ◽

pp. 337-347 ◽

Cited By ~ 2

Author(s):

TOBIAS VOLLKOMMER ◽

ANDERS HENNINGSEN ◽

REINHARD E. FRIEDRICH ◽

OLIVER HEINRICH FELTHAUS ◽

FABIAN EDER ◽

...

Keyword(s):

Foreign Body ◽

Foreign Body Reaction ◽

Porous Polyethylene

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Macroporous methacrylated hyaluronic acid hydrogel with different pore sizes for in vitro and in vivo evaluation of vascularization

Biomedical Materials ◽

10.1088/1748-605x/ac494b ◽

2022 ◽

Author(s):

Daohuan Lu ◽

Zhiwen Zeng ◽

Zhijie Geng ◽

Cuiping Guo ◽

Dating Pei ◽

...

Keyword(s):

Endothelial Cells ◽

Hyaluronic Acid ◽

Pore Size ◽

Umbilical Vein ◽

Gelatin Microspheres ◽

Pore Sizes ◽

And Migration ◽

Proliferation And Migration

Abstract Vascularization of thick hydrogel scaffolds is still a big challenge, because the submicron- or nano-sized pores seriously restrict endothelial cells adhesion, proliferation and migration. Therefore, porous hydrogels have been fabricated as a kind of promising hydrous scaffolds for enhancing vascularization during tissue repairing. In order to investigate the effects of pore size on vascularization, macroporous methacrylated hyaluronic acid (HAMA) hydrogels with different pore sizes were fabricated by a gelatin microspheres (GMS) template method. After leaching out GMS templates, uniform and highly interconnected macropores were formed in hydrogels, which provided an ideal physical microenvironment to induce human umbilical vein endothelial cells (HUVECs) migration and tissue vascularization. In vitro results revealed that macroporous hydrogels facilitated cells proliferation and migration compared with non-macroporous hydrogels. Hydrogels with middle pore size of 200-250 μm (HAMA250 hydrogels) supported the best cell proliferation and furthest 3D migration of HUVECs. The influences of pore sizes on vascularization were then evaluated with subcutaneous embedding. In vivo results illustrated that HAMA250 hydrogels exhibited optimum vascularization behavior. Highest number of newly formed blood vessels and expression of CD31 could be found in HAMA250 hydrogels rather than in other hydrogels. In summary, our results concluded that the best pore size for endothelial cells migration and tissue vascularization was 200-250 μm. This research provides a new insight into the engineering vascularized tissues and may find utility in designing regenerative biomaterial scaffolds

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Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

Current Drug Delivery ◽

10.2174/1567201818666201214125237 ◽

2020 ◽

Vol 18 ◽

Author(s):

Zirui Zhang ◽

Shangcong Han ◽

Panpan Liu ◽

Xu Yang ◽

Jing Han ◽

...

Keyword(s):

Wound Healing ◽

Mrna Expression ◽

Tissue Injury ◽

Inflammatory Cells ◽

Pcr Analysis ◽

Protective Effects ◽

Deep Tissue ◽

Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics10040227 ◽

2018 ◽

Vol 10 (4) ◽

pp. 227 ◽

Cited By ~ 9

Author(s):

Bayan Darwesh ◽

Hibah Aldawsari ◽

Shaimaa Badr-Eldin

Keyword(s):

Vaginal Delivery ◽

Polyelectrolyte Complex ◽

Inflammatory Cells ◽

Antifungal Drugs ◽

Vaginal Candidiasis ◽

Histological Evaluation ◽

Anionic Polymer ◽

In Vivo Evaluation

(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3151 factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol® 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.

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Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.266.6.l593 ◽

1994 ◽

Vol 266 (6) ◽

pp. L593-L611 ◽

Cited By ~ 13

Author(s):

M. D. Evans ◽

W. A. Pryor

Keyword(s):

Cigarette Smoke ◽

Proteinase Inhibitor ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Lung Lavage ◽

Tissue Destruction ◽

Phagocytic Cells ◽

Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

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