scholarly journals The Granule Size Mediates the In Vivo Foreign Body Response and the Integration Behavior of Bone Substitutes

Materials ◽  
2021 ◽  
Vol 14 (23) ◽  
pp. 7372
Author(s):  
Manuel Abels ◽  
Said Alkildani ◽  
Annica Pröhl ◽  
Xin Xiong ◽  
Rumen Krastev ◽  
...  
Keyword(s):  
Granulation Tissue ◽  
Bone Substitute ◽  
Degradation Process ◽  
Bone Substitutes ◽  
Granule Size ◽  
Foreign Body Response ◽  
Surrounding Tissue ◽  
Bony Tissue ◽  
Tissue Integration

The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.

scholarly journals Supplementation with 45S5 Bioactive Glass Reduces In Vivo Resorption of the β-Tricalcium-Phosphate-Based Bone Substitute Material Vitoss

2019 ◽  
Vol 20 (17) ◽  
pp. 4253 ◽  
Author(s):  
Fabian Westhauser ◽  
Christopher Essers ◽  
Maria Karadjian ◽  
Bruno Reible ◽  
Gerhard Schmidmaier ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Tricalcium Phosphate ◽  
Bone Substitute ◽  
Degradation Kinetics ◽  
Bone Substitutes ◽  
Micro Computed Tomography ◽  
Immunodeficient Mice ◽  
Bone Substitute Materials ◽  
Osseous Regeneration

Compared to other materials such as 45S5 bioactive glass (BG), β-tricalcium phosphate (β-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of β-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of β-TCP/45S5-BG composite bone substitute materials.

3D Microtomography Characterization of Dental Implantology Bone Substitutes Used In Vivo

2013 ◽  
Vol 541 ◽  
pp. 97-113 ◽  
Author(s):  
Rossella Bedini ◽  
Deborah Meleo ◽  
Raffaella Pecci
Keyword(s):  
Bone Substitute ◽  
Histological Analysis ◽  
Research Work ◽  
Bone Substitutes ◽  
Human Bone ◽  
Histological Techniques ◽  
In Vitro Characterization

After a short introduction to bone substitute biomaterials and X-ray microtomography, this article describes a research work carried out for in-vitro characterization of bone substitute biomaterials as well as for in-vivo investigation of human bone grafted with biomaterials. Three different bone substitute biomaterials have been analyzed in-vitro by means of 3D microtomographic technique, while human bone samples grafted with bone substitute biomaterials are investigated by 3D microtomography and histological techniques. 3D images of bone substitutes and human bone samples with biomaterials have been obtained, together with morphometric parameters, by microtomography . 2D histological images have also been obtained by traditional technique only for human bone samples with biomaterials. Compared to traditional histological analysis, 3D microtomography shows better results for investigating bone tissue and bone substitute biomaterial, and in a short time. Nevertheless, histological analysis remains the best technique for the observation of soft tissue and blood vessels.

IN VIVO EVALUATION OF A NEW β-TRICALCIUM PHOSPHATE BONE SUBSTITUTE IN A RABBIT FEMUR DEFECT MODEL

2015 ◽  
Vol 27 (03) ◽  
pp. 1550028 ◽  
Author(s):  
Kam-Kong Chan ◽  
Chia-Hsien Chen ◽  
Lien-Chen Wu ◽  
Yi-Jie Kuo ◽  
Chun-Jen Liao ◽  
...  
Keyword(s):  
Bone Graft ◽  
Tricalcium Phosphate ◽  
Bone Substitute ◽  
Zealand White Rabbit ◽  
Bone Substitutes ◽  
Bone Graft Substitute ◽  
Defect Model ◽  
In Vivo Evaluation ◽  
Rabbit Femur

Calcium phosphate ceramics, of a similar composition to that of mineral bone, and which possess the properties of bioactivity and osteoconductivity, have been widely used as substitutes for bone graft in orthopedic, plastic and craniofacial surgeries. A synthetic β-tricalcium phosphate, Osteocera™, a recently developed bone graft substitute, has been used in this study. To evaluate the affinity and efficacy of Osteocera™ as bone defect implant, we used a New Zealand white rabbit femur defect model to test the osteoconductivity of this new bone substitute. Alternative commercially available bone substitutes, Triosite® and ProOsteon500, were used as the control materials. These three bone substitutes show good biocompatibility, and no abnormal inflammation either infection was seen at the implantation sites. In the histological and histomorphometric images, newly formed bone grew into the peripheral pores in the bone substitutes. After six months implantation, the volume of bone formation was found to be 20.5 ± 5.2%, 29.8 ± 6.5% and 75.5 ± 4.9% of the potential total cavity offered by ProOsteon500, Triosite® and Osteocera™, respectively. The newly formed bone area within the femur defect section for Osteocera™ was significantly larger than ProOsteon500 and Triosite®. We concluded that Osteocera™ shows better bioresorbability, biocompatibility and osteoconductivity in the rabbit femur defect model.

scholarly journals Mesenchymal Stem/Progenitor Cell Isolation from Tooth Extraction Sockets

2014 ◽  
Vol 93 (11) ◽  
pp. 1133-1140 ◽  
Author(s):  
R. Nakajima ◽  
M. Ono ◽  
E.S. Hara ◽  
Y. Oida ◽  
S. Shinkawa ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Granulation Tissue ◽  
Tooth Extraction ◽  
Alveolar Bone ◽  
Fibrous Tissue ◽  
Flow Cytometric Analysis ◽  
Primary Source ◽  
Control Group ◽  
Bony Tissue

Bone marrow–derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach. It is well known that stem cells migrate from surrounding tissues and play important roles in wound healing. We thus hypothesized that stem/progenitor cells could be isolated from granulation tissue in the dental socket, and we subsequently collected granulation tissue from dog dental socket 3 d after tooth extraction. After enzyme digestion of the collected tissue, the cells forming colonies constituted the dental socket–derived stem/progenitor cells (dDSCs). Next, dDSCs were compared with dog BMSCs (dBMSCs) for phenotype characterization. A flow cytometric analysis showed that dDSCs were positive for CD44, CD90, and CD271 but negative for CD34 and CD45, similar to dBMSCs. dDSCs also exhibited osteogenic, adipogenic, and chondrogenic differentiation ability, similar to dBMSCs, with a higher capacity for colony formation, proliferation, and motility than dBMSCs. In addition, an in vivo ectopic bone formation assay showed that dDSCs and dBMSCs both induced hard tissue formation, although only dDSCs formed a fibrous tissue-like structure connected to the newly formed bone. Finally, we tested the ability of dDSCs to regenerate periodontal tissue in a one-wall defect model. The defects in the dDSC-transplanted group (β-TCP/PGA/dDSCs) were regenerated with cementum-like and periodontal ligament-like tissues and alveolar bone, whereas only bony tissue was observed in the control group (β-TCP/PGA). In conclusion, we identified and characterized a population of stem/progenitor cells in granulation tissue obtained from the dental socket that exhibited several characteristics similar to those of BMSCs. Dental sockets could therefore be a novel source for isolating stem/progenitor cells from bone.

scholarly journals Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

2021 ◽  
Vol 22 (9) ◽  
pp. 4442
Author(s):  
Mike Barbeck ◽  
Marie-Luise Schröder ◽  
Said Alkildani ◽  
Ole Jung ◽  
Ronald E. Unger
Keyword(s):  
Bone Substitute ◽  
Cytokine Expression ◽  
Granule Size ◽  
Physical Characteristics ◽  
Cytokine Gene Expression ◽  
Pore Sizes ◽  
Gm Csf ◽  
Bone Substitute Materials ◽  
Substitute Materials

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.

10 Analysis of the in vivo course of foreign body response to a phycogenic bone substitute using FTIR spectroscopy

2021 ◽  
pp. 117-122
Author(s):  
Žarko Mitić ◽  
Sanja Stojanović ◽  
Stevo Najman ◽  
Mike Barbeck ◽  
Miroslav Trajanović
Keyword(s):  
Foreign Body ◽  
Ftir Spectroscopy ◽  
Bone Substitute ◽  
Foreign Body Response ◽  
Body Response

scholarly journals Biocompatible Nanocomposite Implant with Silver Nanoparticles for Otology—In Vivo Evaluation

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 764 ◽  
Author(s):  
Magdalena Ziąbka ◽  
Elżbieta Menaszek ◽  
Jacek Tarasiuk ◽  
Sebastian Wroński
Keyword(s):  
Silver Nanoparticles ◽  
Middle Ear ◽  
Granulation Tissue ◽  
Ex Vivo ◽  
Healing Process ◽  
Silver Ions ◽  
In Vivo Studies ◽  
Surrounding Tissue ◽  
Injection Moulding Process

The aim of this work was to investigate of biocompatibility of polymeric implants modified with silver nanoparticles (AgNPs). Middle ear prostheses (otoimplants) made of the (poly)acrylonitrile butadiene styrene (ABS) and ABS modified with silver nanoparticles were prepared through extrusion and injection moulding process. The obtained prostheses were characterized by SEM-EDX, micro-CT and mechanical tests, confirming their proper shape, good AgNPs homogenization and mechanical parameters stability. The biocompatibility of the implants was evaluated in vivo on rats, after 4, 12, 24 and 48 weeks of implantation. The tissue-healing process and cytotoxicity of the implants were evaluated on the basis of microscopic observations of the materials morphology after histochemical staining with cytochrome c oxidase (OCC) and acid phosphatase (AP), as well as via micro-tomography (ex vivo). The in vivo studies confirmed biocompatibility of the implants in the surrounding tissue environment. Both the pure ABS and nanosilver-modified ABS implants exhibited a distinct decrease in the area of granulation tissue which was replaced with the regenerating muscle tissue. Moreover, a slightly smaller area of granulation tissue was observed in the surroundings of the silver-doped prosthesis than in the case of pure ABS prosthesis. The kinetics of silver ions releasing from implants was investigated by ICP-MS spectrometry. The measurement confirmed that concentration of the silver ions increased within the implant’s immersion period. Our results showed that middle ear implant with the nanoscale modification is biocompatible and might be used in ossicular reconstruction.

Comparative Critical Study of Commercial Calcium Phosphate Bone Substitutes in Terms of Physic-Chemical Properties

2013 ◽  
Vol 587 ◽  
pp. 63-68 ◽  
Author(s):  
T. Miramond ◽  
Pascal Borget ◽  
Serge Baroth ◽  
Daculsi Guy
Keyword(s):  
Bone Substitute ◽  
Calcium Phosphates ◽  
Chemical Properties ◽  
Quality Criteria ◽  
Bone Substitutes ◽  
Critical Study ◽  
Chemical Characteristics ◽  
Bioactive Properties ◽  
Physico Chemical

Physico-chemical characteristics impact directly or indirectly the bioactive properties of biomaterials, it is then essential to correlate it with their effect in vivo. A panel of biomaterials available on the market, based on Hydroxyapatite (HA) and Tricalcium phosphate (β-TCP) is studied in terms of surface area, hydrophilicity, porosity, zeta potential, crystalline phases and density. This study highlights the dispersity of commercial calcium phosphates (CaP) properties, and demonstrates how the quality criteria required for such bone substitute based on biomimicry concept, whose pores distribution is certainly the more relevant, are often incompletely or not respected according to literature.

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

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.

scholarly journals ROS-Degradable Polythioketal Urethane Foam Dressings to Promote Porcine Skin Wound Repair

2021 ◽  
Author(s):  
Prarthana Patil ◽  
Katherine A Russo ◽  
Joshua T McCune ◽  
Alonda C Pollins ◽  
Matthew A Cottom ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Degradation Products ◽  
Skin Wound ◽  
Foreign Body Response ◽  
Skin Wound Healing ◽  
Tissue Integration ◽  
Wound Matrix

Impaired skin healing and progression into chronic wounds is a prevalent and growing medical problem. Porous, resorbable biomaterials can be used as temporary substrates placed into skin defects to support cell infiltration, neo-tissue formation, and remodeling of nonhealing wounds. Naturally-derived biomaterials have promising healing benefits, but their low mechanical properties and exuberant costs limit their performance and use. Synthetic materials can be affordably manufactured and tuned across a broader range of physiochemical properties, but opportunities remain for tailoring them for ideal host immune and regenerative responses. Polyesters are the most clinically-tested class of synthetic biomaterials, but their hydrolysis releases acidic degradation products that can cause autocatalytic degradation processes that are poorly controlled and are not tied to cellular or other biologic activities. Here, we systemically explored a series of ROS-degradable polythioketal (PTK) urethane (UR) foams with varied hydrophilicity as an alternative class of synthetic biomaterials for wound healing. It was found that the most hydrophilic PTK-UR variant, which had 7 ethylene glycol (EG7) repeats flanking each side of each thioketal bond, had the highest ROS reactivity of the PTK-URs tested. In an in vivo porcine excisional skin wound healing model, hydrophilic EG7 PTK-UR foams more effectively promoted tissue integration, ECM deposition, and re-epithelialization of full-thickness skin wound compared to more hydrophobic PTK-UR variants. Resolution of type 1 inflammation and lower foreign body response to scaffold remnants was also observed for EG7 versus more hydrophobic PTK-UR scaffolds. Finally, porcine wound healing studies showed that EG7 PTK-UR foams had similar wound healing response to a collagen-based clinical gold standard product, Integra Bilayer Wound Matrix (BWM), while outperforming polyester UR foam-based NovoSorb Biodegradable Temporizing Matrix (BTM) with respect to increased ECM production, vascularization, and biomaterial-associated immune phenotype. In sum, PTK-UR foams warrant further development toward a new class of synthetic biomaterial foams for skin wound healing applications.

Sign in / Sign up

Export Citation Format

Share Document