Subcutaneous Implantation In Rats Research Articles

Electrostatic Flocking of Insulative and Biodegradable Polymer Microfibers for Biomedical Applications.

Electrostatic flocking, a textile engineering technique, uses Coulombic driving forces to propel conductive microfibers toward an adhesive-coated substrate, leaving a forest of aligned fibers. Though an easy way to induce anisotropy along a surface, this technique is limited to microfibers capable of accumulating charge. This study reports a novel method, utilizing principles from the percolation theory to make electrically insulative polymeric microfibers flockable. A variety of well-mixed, conductive materials are added to multiple insulative and biodegradable polymer microfibers during wet spinning, which enables nearly all types of polymer microfibers to accumulate sufficient charges required for flocking. Biphasic, biodegradable scaffolds are fabricated by flocking silver nanoparticle (AgNP)-filled poly(ε-caprolactone) (PCL) microfibers onto substrates made from 3D printing, electrospinning, and thin-film casting. The incorporation of AgNP into PCL fibers and use of chitosan-based adhesive enables antimicrobial activity against methicillin-resistant Staphylococcus aureus. The fabricated scaffolds demonstrate both favorable in vitro cell response and new tissue formation after subcutaneous implantation in rats, as evident by newly formed blood vessels and infiltrated cells. This technology opens the door for using previously unflockable polymer microfibers as surface modifiers or standalone structures in various engineering fields.

Freeze-Casting with 3D-Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration.

A new approach is described for fabricating 3D poly(ε-caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze-casting with 3D-printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D-printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro-/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)-mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.

Improving in vitro and in vivo corrosion resistance and biocompatibility of Mg–1Zn–1Sn alloys by microalloying with Sr

Magnesium (Mg) and its alloys have attracted attention as potential biodegradable materials in orthopedics due to their mechanical and physical properties, which are compatible with those of human bone. However, the effect of the mismatch between the rapid material degradation and fracture healing caused by the adverse effect of hydrogen (H2), which is generated during degradation, on surrounding bone tissue has severely restricted the application of Mg and its alloys. Thus, the development of new Mg alloys to achieve ideal degradation rates, H2 evolution and mechanical properties is necessary. Herein, a novel Mg–1Zn–1Sn-xSr (x = 0, 0.2, 0.4, and 0.6 wt%) quaternary alloy was developed, and the microstructure, mechanical properties, corrosion behavior and biocompatibility in vitro/vivo were investigated. The results demonstrated that a minor amount of strontium (Sr) (0.2 wt %) enhanced the corrosion resistance and mechanical properties of Mg–1Zn–1Sn alloy through grain refinement and second phase strengthening. Simultaneously, due to the high hydrogen overpotential of tin (Sn), the H2 release of the alloys was significantly reduced. Furthermore, Sr-containing Mg–1Zn–1Sn-based alloys significantly enhanced the viability, adhesion and spreading of MC3T3-E1 cells in vitro due to their unique biological activity and the ability to spontaneously form a network structure layer with micro/nanotopography. A low corrosion rate and improved biocompatibility were also maintained in a rat subcutaneous implantation model. However, excessive Sr (>0.2 wt %) led to a microgalvanic reaction and accelerated corrosion and H2 evolution. Considering the corrosion resistance, H2 evolution, mechanical properties and biocompatibility in vitro and in vivo, Mg–1Zn–1Sn-0.2Sr alloy has tremendous potential for clinical applications.

Robust Electrospun Nanofibers from Chemosynthetic Poly(4-hydroxybutyrate) as Artificial Dural Substitute.

Bioresorbable poly(4-hydroxybutyrate) (P4HB) may fulfill the specific requirements that are necessary for a dural substitute, including its high elasticity, long-term strength retention properties, and the biocompatibility without significant accumulation of acidic degradation products. However, commercial P4HB can only be produced by the bacterial fermentation, which limits its applications in the cerebrospinal system due to higher endotoxin restriction. Meanwhile, P4HB can be prepared via the ring-opening polymerization of γ-butyrolactone. In this contribution, high molecular weight P4HB from chemosynthesis is electrospun into fibrous membrane, showing good mechanical properties that match the natural dura mater. Such P4HB membrane induces fast cellular migration, adhesion, and proliferation of fibroblasts in vitro. Subcutaneous implantation in rats demonstrates excellent biocompatibility of the P4HB membrane with proper biodegradation behaviors. After implantation in the rabbit dural defect model as an onlay graft, the P4HB membranes prevent cerebrospinal fluid leakage and regenerate dura tissue without detecting any local or systematic infections or foreign body responses. Thus, the electrospun P4HB membranes may be particularly useful as artificial dural substitutes to induce wound closure and tissue regeneration, which will be of great benefit to neurosurgery in the future.

MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion

Adhesion formation during tendon healing remains a severe problem in clinical practice. Multiple factors contribute to postoperative adhesion formation, and macrophage-driven inflammation is thought to be greatly involved in this process. We hypothesize that reducing macrophage-mediated inflammation in the injured tendon by regulating M1 to M2 macrophage polarization may effectively inhibit adhesion formation. Here, we developed an acellular immunomodulatory biomaterial consisting of an electrospun polycaprolactone/silk fibroin (PCL/SF) composite fibrous scaffold functionalized with mesenchymal stem cell (MSC)-derived extracellular matrix (ECM). To enhance the immunoregulatory potential of MSCs, we performed inflammatory licensing with IFN-γ to obtain immunomodulatory ECM (iECM). Proteomic analyses of MSCs and their secreted ECM components from different culture conditions revealed the MSC-ECM molecular signatures and the potential mechanism of ECM immunoregulation. Then, the immunoregulatory potential of the iECM-modified scaffold was evaluated in vitro and in vivo. Relative to the PCL/SF fibrous scaffold, the iECM-functionalized scaffold facilitated M2 macrophage polarization and inhibited the expression of multiple cytokines (IL-1β, IL-6, CXCL11, IL-10, IL-1R2, and TGF-β1) in vitro, strongly suggesting the immunosuppressive ability of iECM derived from inflammatory licensed MSCs. Consistent with the in vitro findings, the results of rat subcutaneous implantation indicated that a markedly lower foreign-body reaction (FBR) was obtained in the PCL/SF-iECM group than in the other groups, as evidenced by thinner fibrotic capsule formation, less type I collagen production and more M2-type macrophage polarization. In the rat Achilles tendon injury model, the PCL/SF-iECM scaffold greatly mitigated tendon adhesion with clear sheath space formation between the tendon and the scaffold. These data highlight the immunomodulatory potential of iECM-functionalized fibrous scaffolds to attenuate FBR by modulating M2 macrophage polarization, thereby preventing tendon adhesion. Statement of significanceElectrospun PCL/SF fibrous scaffolds functionalized with ECM secreted by MSCs stimulated by inflammatory factor IFN-γ was developed that combined physical barrier and immunomodulatory functions to prevent tendon adhesion formation. PCL/SF micro-nanoscale bimodal fibrous scaffolds prepared by emulsion electrospinning possess high porosity and a large pore size beneficial for nutrient transport to promote intrinsic healing; moreover, surface modification with immunomodulatory ECM (iECM) mitigates the FBR of fibrous scaffolds to prevent tendon adhesion. The iECM-functionalized electrospun scaffolds exhibit powerful immunomodulatory potency in vitro and in vivo. Moreover, the iECM-modified scaffolds, as an anti-adhesion physical barrier with immunomodulatory ability, have an excellent performance in a rat Achilles tendon adhesion model. MSC secretome-based therapeutics, as an acellular regenerative medicine strategy, are expected to be applied to other inflammatory diseases due to its strong immunoregulatory potential.

Surface modification of electrospun fibers with mechano-growth factor for mitigating the foreign-body reaction

The implantation of synthetic polymeric scaffolds induced foreign-body reaction (FBR) seriously influence the wound healing and impair functionality recovery. A novel short peptide, mechano-growth factor (MGF), was introduced in this study to modify an electrospun polycaprolactone (PCL) fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR. In vitro studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins. We found that macrophages response the MGF stimuli via endocytosis, then MGF promotes the histone acetylation and upregulates the STAT6 expression to direct an anti-inflammatory phenotype transition. Subsequently, an immunoregulatory electrospun PCL fibrous scaffold was modified by silk fibroin (SF) single-component layer-by-layer assembly, and the SF was decorated with MGF via click chemistry. Macrophages seeded on scaffold to identify the function of MGF modified scaffold in directing macrophage polarization in vitro. Parallelly, rat subcutaneous implantation model and rat tendon adhesion model were performed to detect the immunomodulatory ability of the MGF-modified scaffold in vivo. The results demonstrate that MGF-modified scaffold is beneficial to the transformation of macrophages to M2 phenotype in vitro. More importantly, MGF-functionalized scaffold can inhibit the FBR at the subcutaneous tissue and prevent tissue adhesion.

CLINICAL ANALYSIS OF BLOOD TRACES OF RATS AFTER SUBCUTANEOUS IMPLANTATION OF Nd-Fe-B MAGNETS WITH PROTECTIVE PVD ZrN COATINGS

It is possible to increase the effectiveness of treatment of various anomalies of occlusion with the help of orthodontic appliances, including permanent magnets as components. But a significant disadvantage of magnetic materials is low corrosion resistance, which can be prevented by applying to the magnets various PVD protective coatings leading to passivation of the surface of the magnetic material. The effect of Nd-Fe-B magnets with and without protective ZrN coating after subcutaneous implantation in rats on the results of laboratory blood tests has been evaluated.

New prospects in skin regeneration and repair using nanophased hydroxyapatite embedded in collagen nanofibers

This study reflects an exploitation of a composite matrix produced by electrospinning of collagen and electrospraying of nanophased hydroxyapatite (nanoHA), for skin regeneration applications. The main goal was to evaluate the effect of nanoHA, as source of localized calcium delivery, on human dermal fibroblasts, keratinocytes, and human mesenchymal stem cells (hMSCs) growth, proliferation, differentiation, and extracellular matrix production. This study revealed that calcium ions provided by nanoHA significantly enhanced cellular growth and proliferation rates and prevented adhesion of pathogenic bacteria strains typically found in human skin flora. Moreover, hMSCs were able to differentiate in both osteogenic and adipogenic lineages. Rat subcutaneous implantation of the membranes also revealed that no adverse reaction occurred. Therefore, the mechanically fit composite membrane presents a great potential to be used either as cell transplantation scaffold for skin wound regeneration or as wound dressing material in plastic surgery, burns treatment or skin diseases.

Subcutaneous Surgical Rat Models for the Evaluation of Tissue-Engineered Heart Valve Immunogenicity: A Systematic Review

Background: Tissue engineered heart valves are being designed as alternative valvular conduits to standard bioprostheses with the potential to meet the requirements of an ideal valvular prosthesis: non-thrombogenicity, non-immunogenicity, long-lasting, and capability of growth, repair, and remodelling upon implantation. Assessments of immunogenicity are required before in vivo testing in large animals may be undertaken. Rats are a cost-effective model that are widely used for such assessments. However, it is unclear whether the surgical rat models used for examining tissue immunogenicity are homogenous in their design. Methods: Systematic searches were conducted in the PubMed, Scopus, and Web of Science databases for articles in which the immunogenicity of tissue engineered heart valves was examined using subcutaneous surgical rat models. Assessments were made of the animal, surgical, and donor scaffold characteristics used in such models. The heterogeneity of the various characteristics was then evaluated qualitatively. Results: In total, 54 articles were qualitatively assessed in this systematic review. The donor scaffold characteristics were homogenous. Whereas, the animal and surgical characteristics were heterogenous and infrequently reported. The collective data suggest that an agreed subcutaneous rat model might consist of implanting four, 1 cm2, tissue engineered heart valve samples in the dorsal aspect of 6-week-old, Sprague Dawley, rats. Conclusions: Rat subcutaneous implantation may be undertaken to assess the immunogenicity of tissue engineered heart valves before proceeding to in vivo studies in large animal models. There is significant heterogeneity in the characteristics of the subcutaneous rat models that have been used, to date. Most studies insufficiently report the techniques used. Funding Information: This work was supported by funding gratefully received from the Green Lane Research and Education Fund (Greenlane Research and Education Fund, Grafton, Auckland, New Zealand), and the National Heart Foundation of New Zealand (National Heart Foundation of New Zealand, Ellerslie, Auckland, New Zealand). S.W. received a postgraduate scholarship from the National Heart Foundation of New Zealand, M.G. received and Green Lane Research and Education Fund Postgraduate Scholarship, and C.A. received a University of Auckland summer research scholarship. Declaration of Interests: The authors declare that they have no conflicts of interest related to this work.

Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration.

Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO4 incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity-especially the angiogenic ability-is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr-CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr-CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr-CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr-CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr-CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr-CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr-CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.

Comprehensive analyses and prioritization of various swim bladder-derived extracellular matrix in the application of heart valve prosthesis

Calcification-caused failure and deterioration have become the biggest issues facing traditional biological heart valves (BHVs). Thus, developing new source of materials with the ability to resist calcification is an imperative demand of clinical. In our previous work, swim bladder was proved with superb calcification-resistance as a promising candidate for cardiovascular biomaterials. To find the optimal choice of swim bladder, we herein further investigated four types of swim bladders including grass carp (GC), culter alburnus (CA), carp (C) and silver carp (SC) as material source of the BHVs. Data showed that all the swim bladder was mainly composed of elastin fiber, collagen fiber and glycosaminoglycan (GAG). All the groups except GC group can meet the basic mechanical and materials stability requirements as BHVs. Moreover, the calcification of swim bladder derived from SC was proved significantly lower than that of CA and C groups with in vivo rat subcutaneous implantation model. Additionally, in vitro assays demonstrated that four types of swim bladder exhibited well hemocompatibility and cytocompatibility. Collectively, the superior properties including low calcification, adequate mechanical, high stability, as well as excellent hemocompatibility and cytocompatibility of SC-derived swim bladder endow it great competence as BHVs.

Polyzwitterion-crosslinked hybrid tissue with antithrombogenicity, endothelialization, anticalcification properties

Although transcatheter aortic valve implantation (TAVI) has been proven with excellent effectiveness and safety, the subclinical leaflet thrombosis (SLT) and structural valve deterioration (SVD) are two main factors threatening the service lifespan of the transcatheter aortic valve (TAV) because the glutaraldehyde (Glut) crosslinked tissue as leaflet material for the current clinically used TAV has high calcification propensity and thrombogenicity. In this study, zwitterionic monomer sulfobetaine methacrylate (SBMA) and methacrylated porcine pericardium (MA-PP) were in situ copolymerized to obtain zwitterionic-polymer/ tissue hybrid (PSBMA-PP). The hybrid PP showed high collagen stability, appropriate mechanical property, and anti-fatigue performance, meeting the essential requirements as a TAV leaflet. Moreover, the assays of platelet adhesion, in vitro thrombus generation, and ex vivo arteriovenous shunt (AV-shunt) assay suggested that PSBMA-PP had significantly lower thrombogenicity than the non-hybrid porcine pericardium (PMA-PP) and glutaraldehyde crosslinked porcine pericardium (Glut-PP). Interestingly, the introduction of poly-SBMA increased the resistance to the adsorption of non-specific proteins but didn’t compromise the endothelialization potential, promisingly benefitting the long-term hemocompatibility. Meanwhile, the subcutaneous implantation in rats for 120 days showed that PSBMA-PP was able to effectively inhibit the calcification of valve leaflets compared with Glut-PP, which was significant to retard the occurrence of SVD. In conclusion, we developed a simple method to simultaneously functionalize and crosslink the tissue with robust antithrombotic and anticalcification properties for the fabrication of TAV, which was expected to further improve the safety and service life of existing interventional TAV products.

Biocompatiblibility analysis of the decellularized bovine pericardium

The decellularized bovine pericardium and its potential use as a natural scaffold is a promising approach in the field of tissue engineering and regenerative medicine. The reaction of the host toward decellularized scaffolds depends on their biocompatibility, which should be satisfied being before applied in clinical use. Purpose: to evaluate the biocompatibility of the extracellular matrices, which were decellularized by trypsin enzyme and anionic sodium dodecyl sulfate (SDS) detergent. Material and methods. Pericardial sacs were acquired from 12-18 months’ age bulls. Tissue decellularization was performed by using 0.25 % Trypsin solution and 1 % ionic SDS for group I and 0.1 % SDS for group II samples. The implantation was performed on Wistar rats. The tissue samples were stained with hematoxylin & eosin, Congo red and Masson's Trichrome for histological analysis. Results. In group 1 in 3 months after subcutaneous implantation in rats we noticed the inflammation in surrounding tissue and degradation of the implant. Under the same conditions in animals of group 2 implant replacement with growing immature connective tissue was noted. Bio-implant of this group did not degrade, moreover it's integrated to the tissues of experimental rats. Conclusion. Our results showed that decellularized bovine pericardium by 0.1 % SDS can become an alternative material for tissue engineering and has the potential for further use in human surgery.

Synthetic ceramic macroporous blocks as a scaffold in ectopic bone formation induced by recombinant human bone morphogenetic protein 6 within autologous blood coagulum in rats.

We have recently developed an autologous bone graft substitute (ABGS) containing recombinant human bone morphogenetic protein 6 (rhBMP6) in autologous blood coagulum (ABC) that induces new bone formation in vivo. In order to improve biomechanical properties of the implant, compression resistant matrix (CRM) consisting of synthetic ceramics in the form of macroporous cylinders was added to the ABGS and we evaluated the biomechanical properties and the quantity and quality of bone formation following subcutaneous implantation in rats. ABGS implants containing rhBMP6 in ABC with cylindrical ceramic blocks were implanted subcutaneously (n = 6 per time point) in the axillary region of Sprague-Dawley rats and removed at specified time points (7, 14, 21, 35, and 50days). The quantity and quality of newly formed bone were analyzed by microCT, histology, and histomorphometric analyses. Biomechanical properties of ABGS formulations were determined by employing the cut test. MicroCT analyses revealed that ABGS implants induced formation of new bone within ceramic blocks. Histological analysis revealed that on day seven following implantation, the endochondral ossification occupied the peripheral part of implants. On days 14 and 21, newly formed bone was present both around the ceramic block and through the pores inside the block. On both days 35 and 50, cortical bone encircled the ceramic block while inside the block, bone covered the ceramic surface surrounding the pores. Within the osseous circles, there were few trabeculae and bone marrow containing adipocytes. ABGS containing cylindrical ceramic blocks were more rigid and had significantly increased stiffness compared with implants containing ceramic particles as CRM. We demonstrated that macroporous ceramic blocks in a form of cylinders are promising CRMs with good handling and enhanced biomechanical properties, supporting bone formation with ABGS containing rhBMP6 within autologous blood coagulum. Hence, ABGS containing ceramic blocks should be tested in preclinical models including diaphyseal segmental defects and non-unions in larger animals.

Graphene oxide–modified 3D acellular cartilage extracellular matrix scaffold for cartilage regeneration

Articular cartilage regeneration is a challenge in orthopedics and tissue engineering. This study prepared a graphene oxide (GO)-modified 3D acellular cartilage extracellular matrix (ACM) scaffold for cartilage repair. Cartilage slices were decellularized using a combination of physical and chemical methods of fabricating ACM particles. GO was crosslinked with the ACM by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxy succinimide to prepare a composite scaffold. GO modification improved the internal structure and mechanical properties of the scaffold. The GO-modified (2 mg/mL) composite scaffold promoted cell adhesion, cell proliferation, and chondrogenic differentiation in vitro. Experiments on subcutaneous implantation in rats demonstrated that the composite scaffold had good biocompatibility and mild inflammatory response. After 12 weeks of implantation, the composite scaffold loaded with bone marrow mesenchymal stem cells completely bridged the cartilage defects in the rabbit knee with hyaline cartilage. Results indicated that the GO-modified 3D ACM composite scaffold can provide a powerful platform for cartilage tissue engineering and articular cartilage injury treatment.

Tanshinone IIA-loaded aligned microfibers facilitate stem cell recruitment and capillary formation by inducing M2 macrophage polarization

Direct implantation of cell-free scaffolds capable of promoting tissue regeneration by manipulating immune responses has proven to be a promising therapeutic strategy for regenerative medicine. Here, we developed aligned microfiber scaffolds with sustained release of tanshinone ⅡA (Tan ⅡA) to modulate macrophages phenotypic transition, which subsequently promoted stem cell recruitment and capillary formation. Aligned microfibers scaffolds loaded with 1μM Tan ⅡA (AF-1) significantly down-regulated the expression of proinflammatory genes and proteins, while they upregulated anti-inflammatory genes and proteins, in RAW 264.7 macrophages. Conditioned medium collected from macrophages cultured on AF-1 scaffolds enhanced bone marrow-derived mesenchymal stem cell (BMSC) proliferation and migration, and also regulated their multiple biological functions as evidenced by RNA-Seq assays. Moreover, the conditioned medium also promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. Enhancement of endogenous stem cell recruitment and vascularization by regulating macrophage phenotype transition was further confirmed by utilizing rat subcutaneous implantation of the scaffolds. These results support the use of drug-loaded aligned microfiber scaffolds to enable immune modulation to stimulate stem cell recruitment and vascularization, which could potentially result in successful cell-free, scaffold-guided tissue regeneration.

Tough pNAGA hydrogel hybridized porcine pericardium for the pre-mounted TAVI valve with improved anti-tearing properties and hemocompatibility

The rate of adoption of transcatheter aortic valve implantation (TAVI) is increasing rapidly, due to the procedure being less invasive. However, TAVI still faces problems relating to durability, the potential incidence of thrombosis, and the inconvenience of storage in glutaraldehyde (Glut) solution. In this work, a tough hydrogel poly(N-acryloyl glycinamide) (pNAGA) is hybridized with Glut-crosslinked porcine pericardium (Glut-PP) via in situ polymerization and glycerolization, so as to obtain dry leafet material for the fabrication of a pre-mounted bioprosthetic heart valve (BHV). The tensile strength, anti-shearing, and anti-tearing properties of the valve are significantly improved by the process of hydrogel hybridization. Following a period of dry-state compression as a simulation for the crimping process of pre-mounted TAV, pNAGA/Glut-PP showed full recovery without structural damage when fully rehydrated. The introduction of pNAGA also improved the blood compatibility of the tissue, with less clot formation and fewer blood cells adhering to the surface of pNAGA/Glut-PP than is found with Glut-PP. Subcutaneous implantation in rats showed that pNAGA/Glut-PP induced a decreased inflammatory response compared with Glut-PP. These results indicate that the strategy for hybridization with hydrogel could be a potential method for preparing pre-mounted TAVs with an improved performance.

Co-effects of C/Ag dual ion implantation on enhancing antibacterial ability and biocompatibility of silicone rubber

Although silicone implants are the most popular choice around the world for breast augmentation, reconstruction, and revision, due to the poor antibacterial properties and limited biocompatibility of silicone rubber (SR), one of the major complications, capsule contracture, is a lingering problem. To overcome the two main shortcomings, a dual ion implantation technique was applied to modify the surface of SR with the basic skeleton element of organic matter, carbon (C) and the broad-spectrum bactericide, silver (Ag). We present surface characterization, toxicological effects, and evaluation of the mechanical, antibacterial and biocompatible properties of C and Ag co-implanted SR (C/Ag−SRs). After ion implantation, surface roughness and tensile strength of these new materials increased. Biotoxicity was fully assessed by in vitro experiments on human fibroblasts and in vivo experiments on rats, showing that the low-Ag groups met safety standards. Both the anti-bacterial adhesion and bactericidal abilities of C/Ag−SRs were superior to those of SR, which had few antibacterial activities, especially against Staphylococcus epidermidis. With respect to biocompatibility, the adhesion of fibroblasts was promoted, while their proliferation was moderately inhibited on ion-implanted surfaces. After subcutaneous implantation in rats for 7, 30, 90 and 180 d, the capsular thickness around C/Ag−SRs was significantly lower than that around the SR. Additionally, there was no difference in the inflammatory reaction after 7 d of retention in vivo between C/Ag−SRs and SR. The results demonstrate that C/Ag−SRs are desirable shell materials for breast implants.

Inorganic-polymerization crosslinked tissue-siloxane hybrid as potential biomaterial for bioprosthetic heart valves.

Bioprosthetic heart valve (BHV) replacement is increasingly used for treating valve-related diseases worldwide but the current commercially used BHVs treated with glutaraldehyde (Glut) often failed within 12-15 years due to degradation, thrombosis, inferior biocompatibility, and calcification. Herein, 3-glycidyloxypropyl trimethoxysilane (GPTMS) was used to crosslink porcine pericardium (PP) at the concentration (vol/vol) of 0.25%, 1%, 2%, and 4% and their performance for potential application in BHVs was evaluated. The crosslinking mechanism mainly involved the ring-opening of epoxide by amine attack and silanol poly-condensation. The stability of collagen in higher concentration (1%, 2%, and 4%) GPTMS crosslinked PPs (GPTMS-PPs) was clearly increased. GPTMS-PPs showed no cytotoxicity and supported the growth of endothelial cells while Glut-PP did not. GPTMS-PPs were less prothrombotic than Glut-PP. GPTMS-PP crosslinked at 1% concentration showed comparable mechanical properties to Glut-PP while had better anti-tearing performance. The subcutaneous implantation in rat for 30 days showed that GPTMS crosslinking was able to effectively inhibit the calcification of BHV.

Biocompatibility evaluation of heparin-conjugated poly(ε-caprolactone) scaffolds in a rat subcutaneous implantation model.

Vascular grafts prepared from synthetic polymers have serious shortcomings that can be resolved by surface modification, such as by immobilizing heparin. In this study, the mechanical properties, biocompatibility, anticoagulation property, and water contact angle of two heparin-conjugated poly(ε-caprolactone) scaffolds (PCL-hexamethylendiamine-heparin, PCL-HMD-H. PCL-lysine-heparin, PCL-LYS-H) were compared to identify a preferred heparin conjugation method. An evaluation of the subcutaneous tissue biocompatibility of the scaffolds demonstrated that PCL-HMD-H had better endothelial cell proliferation than the PCL-LYS-H and was therefore a promising scaffold candidate for use in vascular tissue-engineering.