Host Tissue Integration Research Articles

Costal Cartilage Graft Repair Osteochondral Defect in a Mouse Model.

Osteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation. Costal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes. At 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur. Costal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.

Preparation of Multi-Functional Quaternary Ammonium Chitosan/Surfactin Hydrogel and its Application in Wound Management.

Hydrogel with a 3D network structure can cover the wound to stop the bleeding and support the host tissue infiltration and integration. In this study, an antibacterial hydrogel with hemostasis and the ability to promote wound healing is proposed. This hydrogel comprised surfactin, polyvinylpyrrolidone, and methacrylic anhydride (MA) grafted quaternary ammonium chitosan (CS-MA). The hydrogel formation is triggered by the ultraviolet-initiated polymerization of CS-MA, while the surfactin is complexed with the hydrogel through hydrogen bonding interaction. The results showed that this hydrogel is an adhesive hydrogel with shape adaptability, which can cover the wound surface and promote contact between the hydrogel and the wound surface. More importantly, this hydrogel can simulate the microenvironment of the primary extracellular matrix and increase collagen deposition, and inflammatory factor transformation. The designing of such a multi-functional hydrogel is expected to provide a novel approach to promoting the healing of wounds.

Cellular infiltration in an injectable sulfated cellulose nanocrystal hydrogel and efficient angiogenesis by VEGF loading

BackgroundCellular infiltration and angiogenesis into implanted biomaterial scaffolds are crucial for successful host tissue integration and tissue regeneration. Cellulose nanocrystal (CNC) is a nano-sized cellulose derivative, which can form an injectable physical gel with salts. Sulfate groups of sulfated CNC (CNC-S) can act as a binding domain to various growth factors and cytokines with a heparin-binding domain for sustained release of them. Vascular endothelial growth factor (VEGF) can promote the proliferation of endothelial cells and angiogenesis. In this study, VEGF-loaded CNC-S hydrogel was evaluated as an injectable scaffold that can induce cellular infiltration and angiogenesis.MethodsCNC-S was hydrolyzed to get desulfated CNC (CNC-DS), which was used as a negative control group against CNC-S. Both CNC-S and CNC-DS hydrogels were prepared and compared in terms of biocompatibility and VEGF release. The hydrogels with or without VEGF loading were subcutaneously injected into mice to evaluate the biocompatibility, cellular infiltration, and angiogenesis induction of the hydrogels.ResultsBoth hydrogels possessed similar stability and shear-thinning behavior to be applicable as injectable hydrogels. However, CNC-S hydrogel showed sustained release (until 8 weeks) of VEGF whereas CNC-DS showed a very fast release of VEGF with a large burst. Subcutaneously injected CNC-S hydrogel showed much enhanced cellular infiltration as well as better biocompatibility with milder foreign body response than CNC-DS hydrogel. Furthermore, VEGF-loaded CNC-S hydrogel induced significant angiogenesis inside the hydrogel whereas VEGF-loaded CNC-DS did not.ConclusionCNC-S possesses good properties as a biomaterial including injectability, biocompatibility, and allowing cellular infiltration and sustained release of growth factors. VEGF-loaded CNC-S hydrogel exhibited efficient angiogenesis inside the hydrogel. The sulfate group of CNC-S was a key for good biocompatibility and the biological activities of VEGF-loaded CNC hydrogel.

Ocean acidification elicits differential bleaching and gene expression patterns in larval reef coral Pocillopora damicornis under heat stress

The successful dispersal of coral larvae is vital to the population replenishment and reef recovery and resilience. Despite that this critical early stage is susceptible to ocean warming and acidification, little is known about the responses of coral larvae to warming and acidification across different biological scales. This study explored the influences of elevated temperature (29 °C versus 33 °C) and pCO2 (500 μatm versus 1000 μatm) on brooded larvae of Pocillopora damicornis at the organismal, cellular and gene expression levels. Heat stress caused bleaching, depressed light-enhanced dark respiration, photosynthesis and autotrophy, whereas high pCO2 stimulated photosynthesis. Although survival was unaffected, larvae at 33 °C were ten-times more likely to settle than those at 29 °C, suggesting reduced capacity to disperse and differentiate suitable substrate. Remarkably, heat stress induced greater symbiont loss at ambient pCO2 than at high pCO2, while cell-specific pigment concentrations of symbionts at 33 °C increased twofold under ambient pCO2 relative to high pCO2, suggesting pCO2-dependent bleaching patterns. Considerable increases in activities of host antioxidants superoxide dismutase (SOD) and catalase (CAT) at 33 °C indicated oxidative stress, whereas lipid peroxidation and caspase activities were contained, thereby restraining larval mortality at 33 °C. Furthermore, the coral host mounted stronger transcriptional responses than symbionts. High pCO2 stimulated host metabolic pathways, possibly because of the boosted algal productivity. In contrast, host metabolic processes and symbiont photosystem genes were downregulated at 33 °C. Interestingly, the upregulation of extracellular matrix genes and glycosaminoglycan degradation pathway at 33 °C was more evident under ambient pCO2 than high pCO2, suggesting compromised host tissue integrity that could have facilitated symbiont expulsion and bleaching. Our results provide insights into how coral larvae respond to warming and acidification at different levels of biological organization, and demonstrate that ocean acidification can mediate thermal bleaching and gene expression in coral larvae under heat stress.

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.Graphical

ST2 deletion accelerates inflammatory-angiogenesis and remodeling in subcutaneous implants in mice.

Implantation of biomedical/synthetic devices to replace and/or repair biological tissues very often induces an adverse healing response (scarce angiogenesis, excessive collagen deposition) which is detrimental to implant functionality and integration to host tissue. Interleukin-33/ST2 axis (IL-33/ST2) has been shown to modulate angiogenic and remodeling processes in several types of injuries. However, its effects on these processes after implantation of synthetic matrix have not been reported. Using synthetic matrix of polyether-polyurethane implanted subcutaneously in mice lacking ST2 receptor (ST2/KO), we characterized neovascularization and matrix remodeling in the fibrovascular tissue induced by the implants. Tissue accumulation was increased inside and around the implants in KO implants relative to the wild type (WT). More intense proliferative activity, using CDC 47 marker, was observed in KO implants compared with that of WT implants. Angiogenesis, using two endothelial cell markers, Von Willebrand Factor (VWF) and vascular endothelial cell VE cadherin and hemoglobin content, increased in implants of KO mice relative to control WT. Remodeling of the newly formed fibrovascular tissue (soluble collagen and PicroSirius Red-stained histological sections) showed predominance of type 1 collagen in ST2-KO implants versus type 3 in control implants. The number of positive cells for caspase-3, apoptotic marker, decreased in ST2 group. Our findings evidenced a role of IL-33/ST2 axis in restraining blood vessel formation and regulating the pattern of matrix remodeling in the fibrovascular tissue induced by synthetic implants. Intervention in this cytokine complex holds potential to accelerate integration of biomaterial and host tissue by improving blood supply and matrix remodeling.

An Injectable Meta-Biomaterial: From Design and Simulation to In Vivo Shaping and Tissue Induction.

A novel type of injectable biomaterial with an elastic softening transition is described. The material enables invivo shaping, followed by induction of 3D stable vascularized tissue. The synthesis of the injectable meta-biomaterial is instructed by extensive numerical simulation as a suspension of irregularly fragmented, highly porous sponge-like microgels. The irregular particle shape dramatically enhances yield strain for invivo stability against deformation. Porosity of the particles, along with friction between internal surfaces, provides the elastic softening transition. This emergent metamaterial property enables the material to reversibly change stiffness during deformation, allowing native tissue properties to be matched over a wide range of deformation amplitudes. After subcutaneous injection in mice, predetermined shapes can be sculpted manually. The 3D shape is maintained during excellent host tissue integration, with induction of vascular connective tissue that persists to the end of one-year follow-up. The geometrical design is compatible with many hydrogel materials, including cell-adhesion motives for cell transplantation. The injectable meta-biomaterial therefore provides new perspectives in soft tissue engineering and regenerative medicine.

Silicon-substituted hydroxyapatite reinforced 3D printed gelatin membrane for guided bone regeneration

Guided bone regeneration (GBR) warrants a bioactive membrane with biocompatibility, host tissue integration, and clinical moldability along with adequate mechanical and physical properties. Hydroxyapatite (HA) incorporated membranes have shown to promote the functional and osteogenic activity of stromal cells towards GBR. Also, many studies have demonstrated that the addition of trace elements such as Silicon-substituted HA (SiHA) accelerates and enhances bioactivity compared to HA. In this study, HA and SiHA were incorporated with gelatin (Gel) which is a biocompatible, low-cost, and cell-attractant, and widely used material for GBR. The three-dimensional printed construct provides for topography with interconnected pores that permit selective cell occlusion; a desirable property for GBR. The objective of the study was to develop, characterize, and study the osteogenic potential of Gel-SiHA membrane for GBR.

Ex Vivo and In Vivo Analysis of a Novel Porcine Aortic Patch for Vascular Reconstruction.

(1) Background: The aim of the present study was the biocompatibility analysis of a novel xenogeneic vascular graft material (PAP) based on native collagen won from porcine aorta using the subcutaneous implantation model up to 120 days post implantationem. As a control, an already commercially available collagen-based vessel graft (XenoSure®) based on bovine pericardium was used. Another focus was to analyze the (ultra-) structure and the purification effort. (2) Methods: Established methodologies such as the histological material analysis and the conduct of the subcutaneous implantation model in Wistar rats were applied. Moreover, established methods combining histological, immunohistochemical, and histomorphometrical procedures were applied to analyze the tissue reactions to the vessel graft materials, including the induction of pro- and anti-inflammatory macrophages to test the immune response. (3) Results: The results showed that the PAP implants induced a special cellular infiltration and host tissue integration based on its three different parts based on the different layers of the donor tissue. Thereby, these material parts induced a vascularization pattern that branches to all parts of the graft and altogether a balanced immune tissue reaction in contrast to the control material. (4) Conclusions: PAP implants seemed to be advantageous in many aspects: (i) cellular infiltration and host tissue integration, (ii) vascularization pattern that branches to all parts of the graft, and (iii) balanced immune tissue reaction that can result in less scar tissue and enhanced integrative healing patterns. Moreover, the unique trans-implant vascularization can provide unprecedented anti-infection properties that can avoid material-related bacterial infections.

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.

Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord.

Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into—and thus integration of host tissue with—implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI.

Characterization of infected, explanted ventricular assist device drivelines: The role of biofilms and microgaps in the driveline tunnel

Driveline infections remain a major complication of ventricular assist device (VAD) implantation. This study aimed to characterize in vivo microbial biofilms associated with driveline infections and host tissue integration of implanted drivelines. A total of 9 infected and 13 uninfected drivelines were obtained from patients with VAD undergoing heart transplantation in Australia between 2016 and 2018. Each driveline was sectioned into 11 pieces of 1.5 cm in length, and each section was examined by scanning electron microscopy (SEM) and viable counts for microbial biofilms. Microorganisms were cultured and identified. Host tissue integration of clinical drivelines was assessed with micro-computed tomography (CT) and SEM. An in vitro interstitial biofilm assay was used to simulate biofilm migration in the driveline tunnel, and time-lapse microscopy was performed. Of the 9 explanted, infected drivelines, all had organisms isolated from varying depths along the velour section of the drivelines, and all were consistent with the swab culture results of the clinically infected exit site. SEM and micro-CT suggested insufficient tissue integration throughout the driveline velour, with microgaps observed. Clinical biofilms presented as microcolonies within the driveline tunnel, with human tissue as the sub-stratum, and were resistant to anti-microbial treatment. Biofilm migration mediated by a dispersal-seeding mechanism was observed. This study of explanted infected drivelines showed extensive anti-microbial-resistant biofilms along the velour, associated with microgaps between the driveline and the surrounding tissue. These data support the enhancement of tissue integration into the velour as a potential preventive strategy against driveline infections by preventing biofilm migration that may use microgaps as mediators.

A biomimetic bi-layered tissue engineering scaffolds for osteochondral defects repair

Osteochondral defects are most commonly characterized by damages to both cartilage and underlying subchondral bone tissues, thus developing bi-layered scaffold that can concurrently regenerate these two specific lineages becomes challenge. In this study, the highly biomimetic bi-layered scaffolds were successfully prepared using human-like-collagen (HLC), hyaluronan (HA) and nano hydroxyapatite (HAP) particles, combined with “liquid phase synthesis” technology, freeze-drying and chemical cross-linking techniques, which was simulated the composition of natural extracellular matrix to repair osteochondral defects. This novel bilayer osteochondral graft had a seamlessly integrated layer structure, suitable pore size, high levels of porosity, and excellent mechanical properties. In vitro cell experiments of the bilayer scaffold indicated that the scaffold could promote the proliferation and adhesion of human bone marrow mesenchymal stem cells. In vivo osteochondral defects and micro-CT experiment revealed that bilayer scaffolds showed complete closure of the defect. Histology confirmed collagen and glycosaminoglycans were deposited in the new matrix of hyaline cartilage and bone in the bilayer scaffold group. Therefore, the developed bionic bilayer scaffold enhanced the regeneration of hyaline cartilage through subchondral bone formation and lateral host-tissue integration. In conclusion, this bilayer scaffold based on HLC could be used as the desired strategy for osteochondral defects regeneration.

Engineering Biomimetic Nanofiber Microspheres with Tailored Size, Predesigned Structure, and Desired Composition via Gas Bubble-Mediated Coaxial Electrospray.

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.

Interleukin-17 mediated immunity during infections with Trypanosoma cruzi and other protozoans

Host resistance during infection with Trypanosoma cruzi, and other protozoans, is dependent on a balanced immune response. Robust immunity against these pathogens requires of the concerted action of many innate and adaptive cell populations including macrophages, neutrophils, dendritic cells, CD4+, and CD8+ T cells and B cells among others. Indeed, during most protozoan infections only a balanced production of inflammatory (TH1) and anti-inflammatory (TH2/regulatory) cytokines will allow the control of parasite spreading without compromising host tissue integrity. The description of TH17 cells, a novel effector helper T cell lineage that produced IL-17 as signature cytokine, prompted the revision of our knowledge about the mechanisms that mediate protection and immunopathology during protozoan infections. In this manuscript we discuss the general features of IL-17 mediated immune responses as well as the cellular sources, effector mechanisms and overall role of IL-17 in the immune response to T. cruzi and other protozoan infections.

Surface modification of corneal prosthesis with nano-hydroxyapatite to enhance in vivo biointegration

The majority of clinical corneal prostheses (KPros) adopt a core-skirt configuration. This configuration is favored owing to the optic core (generally a cylindrical, acrylic-based material, such as PMMA), that not only provides a clear window for the patients’ vision, but also confers resistance to biodegradability. The surrounding skirt (typically a biological material, such as corneal tissue) allows for host tissue integration. However, due to poor biointegration between the dissimilar core and skirt materials, it results in a weak adhesion at the interface, giving rise to clinical complications, such as bacterial infections in the tissue-PMMA interface and device extrusion. Here, we physically immobilized nano-hydroxyapatite (nHAp) on a PMMA cylinder via a dip-coating technique, to create a bioactive surface that improved biointegration in vivo. We established that the nHAp coating was safe and stable in the rabbit cornea over five weeks. More importantly, we found that apoptotic, wound healing and inflammatory responses to nHAp-coated PMMA were substantially milder than to non-coated PMMA. More mature collagen, similar to the non-operated cornea, was maintained in the corneal stroma adjacent to the nHAp-coated implant edge. However, around the non-coated cylinder, an abundant new and loose connective tissue formed, similar to bone tissue response to bioinert scaffolds. As a result of superior biointegration, tissue adhesion with nHAp-coated PMMA cylinders was also significantly enhanced compared to non-coated cylinders. This study set a precedent for the future application of the nHAp coating on clinical KPros. Statement of significanceCurrently, all clinical corneal prostheses utilize as-manufactured, non-surface modified PMMA optic cylinder. The bioinert cylinder, however, has poor biointegration and adhesion with the surrounding biological tissue, which can give rise to postoperative complications, such as microbial invasion in the tissue-PMMA loose interface and PMMA optic cylinder extrusion. In the current study, we showed that surface modification of the PMMA cylinder with bioactive nano-hydroxyapatite (nHAp) significantly enhanced its biointegration with corneal stromal tissue in vivo. The superior biointegration of the nHAp-coated PMMA was signified by a more attenuated corneal wound healing, inflammatory and fibrotic response, and better tissue apposition, as well as a significantly improved corneal stromal tissue adhesion when compared to the non-coated PMMA.

Outcomes of the Shunt Tube Exposure Prevention Study: A Randomized Clinical Trial

To compare the long-term safety and efficacy of amniotic membrane-umbilical cord (AM-UC) and pericardium patch grafts in reducing glaucoma shunt tube exposure. Multicenter, prospective, randomized clinical trial. Adults with uncontrolled glaucoma undergoing glaucoma drainage device (GDD) implantation. Patients were randomized to receive GDD with either AM-UC or pericardium patch grafts to cover GDD tubes. Patients were followed up clinically with anterior segment (AS) OCT to assess patch graft stability and host-tissue integration prospectively. Tube exposure, graft thinning, and graft-related complications. A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67±13 years underwent GGD implantation using Baerveldt (n= 72) or Ahmed valve (n= 9). Tubes were inserted in the anterior chamber (n= 71), sulcus (n= 6), or pars plana (n= 4). Tube ligation was performed with Baerveldt GDD along with fenestration (n= 51) or orphan trabeculectomy (n= 21). Tubes were covered with AM-UC (n= 41) or pericardium (n= 40). The mean follow-up time was 29±8 months (range, 13-40 months). Tube exposure occurred in 1 eye (2%) in the AM-UC group at 3 months and in 2 eyes (5%) in the pericardium group at 2 and 6 months (P= 0.54). Sequential AS OCT showed better host-tissue integration and significantly less graft thinning in the AM-UC group. Early graft thinning (≤3 months) occurred in 5 eyes (12%) in the AM-UC group and in 17 eyes (43%) in the pericardium group (P= 0.002). Late thinning occurred in 2 eyes (5%) and 11 eyes (28%) in the AM-UC and pericardium groups, respectively (P= 0.007). Graft translucency and cosmetic appearance of the AM-UC graft were superior to those of the pericardium graft. No evidence of graft rejection or infection was associated with the patch grafts in either group. Amniotic membrane-umbilical cord grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. Its high-tensile strength, low immunogenicity, and excellent host-tissue integration significantly reduced graft thinning.

Hybrid nanocomposite as a chest wall graft with improved integration by adipose-derived stem cells

Surgery of the chest wall is potentially required to cover large defects after removal of malignant tumours. Usually, inert and non-degradable Gore-Tex serves to replace the missing tissue. However, novel biodegradable materials combined with stem cells are available that stimulate the healing. Based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) and pure PLGA, a dual layer biodegradable hybrid nanocomposite was generated. Mouse adipose-derived stem cells were cultered on electrospun disks (ASCs of C57BL/6), and biomechanical tests were performed. The cell-seeded scaffolds were engrafted in C57BL/LY5.1 mice to serve as a chest wall substitute. Cell invasion into the bi-layered material, extent of CD45+ cells, inflammatory response, neo-vascularization and ECM composition were determined at 1 and 2 months post-surgery, respectively. The bi-layered hybrid nanocomposite was stable after a 2-week in vitro culture, in contrast to PLGA/aCaP without a PLGA layer. There was a complete biointegration and good vascularization in vivo. The presence of ASCs attracted more CD45+ cells (hematopoietic origin) compared to cell-free scaffolds. Inflammatory reaction was similar for both groups (±ASCs) at 8 weeks. A bi-layered hybrid nanocomposite fabricated of electrospun PLGA/aCaP and a reinforcing layer of pristine PLGA is an ideal scaffold for chest wall reconstruction. It is stable and allows a proper host tissue integration. If ASCs are seeded, they attract more CD45+ cells, supporting the regeneration process.

Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.

Structural assessments in decellularized extracellular matrix of porcine semilunar heart valves: Evaluation of cell niches.

Tissue-engineered heart valves aim to reproduce the biological properties of natural valves with anatomically correct structure and physiological performance. The closest alternative to creating an ideal heart valve substitute is to use decellularized porcine heart valves, due to their anatomy and availability. However, the immunological barrier and the structural maintenance limit the long-term physiological performance of decellularized porcine heart valves. This study investigated the extracellular matrix (ECM) structure of aortic and pulmonary porcine valves decellularized by a low concentration sodium dodecyl sulfate (SDS)-based method in order to determine the ECM scaffold (ECMS) conditions related to remodeling potential. To assess the structures of the leaflets and conduits of the heart valves, ECM components and their organization were evaluated by histology, biochemical analysis (BC), scanning electron microscopy, multiphoton microscopy, tensile test, immunofluorescence labeling (IF), and Raman microspectroscopy used to draw a profile of the cell niches. Histology and multiphoton imaging of decellularized aortic and pulmonary leaflets and conduits revealed a collagen and elastin histoarchitecture with rearrangement, loosening fibers, and glycosaminoglycan depletion confirmed by biochemistry quantification. The potential cytotoxicity of SDS residues was eliminated after 10 wash cycles. The mechanical properties of the structure of the valve indicated a functional resistance of decellularized ECM. The IF demonstrated the presence of basement membrane, suggesting a potential structure for host cell attachment. The RM analysis showed evidence of molecular interactions, suggesting conservation of the chemical composition, particularly among the protein molecular structures. The structural analyses performed in the semilunar porcine heart valves demonstrate that decellularized ECMS has structural properties that support physiological performance and potential host tissue integration. In fact, decellularized leaflet scaffolds were prone to cell interaction after human adipose-derived stromal cell seeding and culturing. Further analysis of biocompatibility, particularly the ECM-cell interaction, can elucidate the remodeling process, in preserved decellularized heart valve scaffold.