Minimal Inflammatory Response Research Articles

Acellular Dermal Matrix Susceptibility to Collagen Digestion: Effect on Mechanics and Host Response.

Various tissue origins and manufacturing processes can differentially affect the retention of native properties of acellular dermal matrices (ADMs); however, comparative studies are limited. Head-to-head comparisons between different configurations of porcine-derived Strattice (Allergan Aesthetics, an AbbVie Company, Irvine, CA) and bovine-derived SurgiMend (Integra LifeSciences, Billerica, MA) ADMs were performed to evaluate mechanical integrity and host tissue biologic response. Thermodynamic profile and morphology, which affect retention of mechanical strength, were evaluated through differential scanning calorimetry, scanning electron microscopy, and histology. Mechanical strength was assessed through tensile testing following collagenase exposure in vitro and following subcutaneous implantation in a rodent model. Host biologic response was evaluated through histopathology. Compared with respective native tissues, reductions in onset melting temperature following tissue processing were smaller for Strattice Firm versus SurgiMend 1.0 (Δ0.79°C vs. Δ5.77°C), Strattice Extra Thick versus SurgiMend 3.0 (Δ1.57°C vs. Δ4.79°C), and Strattice Perforated versus SurgiMend Microperforated (Δ1.18°C vs. Δ7.76°C), with similar trends for peak melting temperature. Strattice maintained native dermal architecture versus compacted collagen with process-induced interstices observed for SurgiMend. Strattice Firm, Extra Thick, and Perforated retained 33.44%, 65.65%, and 17.20% of initial strength after 48 h exposure to excess collagenase, while the SurgiMend ADMs were completely digested by 48 h. At 6 weeks postimplantation, both Strattice and SurgiMend showed minimal inflammatory response, but greater fibroblast repopulation was evident for Strattice. Strattice Firm had higher maximum load (145.85 ± 33.05 N/cm vs. 24.29 ± 12.35 N/cm, p ≤ 0.01), maximum stress (8.20 ± 1.91 MPa vs. 2.24 ± 1.27 Mpa, p ≤ 0.01), and stiffness (7491.00 ± 1981.32 N/cm vs. 737.56 ± 292.55 N/cm, p ≤ 0.01) than SurgiMend 1.0. Strattice Extra Thick had lower maximum load (198.54 ± 58.79 N/cm vs. 303.08 ± 76.76 N/cm, p < 0.05) than SurgiMend 3.0, but similar maximum stress (6.96 ± 1.78 Mpa vs. 8.73 ± 2.15 Mpa) and stiffness (13386.11 ± 3123.28 N/cm vs. 9389.02 ± 4860.67 N/cm). Strattice Perforated had higher maximum load (72.65 ± 41.44 N/cm vs. 10.23 ± 4.67 N/cm, p < 0.05) and maximum stress (4.08 ± 2.08 Mpa vs. 0.44 ± 0.19 p < 0.05) than SurgiMend Microperforated. Maximum load retention rates following implantation were higher for Strattice Firm versus SurgiMend 1.0 (37.85% vs. 8.03%), Strattice Extra Thick versus SurgiMend 3.0 (45.03% vs. 37.80%), and Strattice Perforated versus SurgiMend Microperforated (28.04% vs. 6.21%). Similar results were obtained for maximum stress and stiffness. In conclusion, Strattice retained greater mechanical strength in vitro and in vivo, while exhibiting greater fibroblast cell infiltration. Impact statement Acellular dermal matrix (ADM)-derived surgical meshes are used in abdominal wall reconstruction procedures, such as hernia repair. Comparative studies evaluating the mechanical properties of ADMs and how they integrate with host tissue are essential because these properties impact performance in a clinical setting. This study compared the maintenance of mechanical integrity and host tissue biologic response of two commercially available ADMs, Strattice and SurgiMend, using in vitro and in vivo techniques. A better understanding of the properties of ADMs is expected to impact mesh selection and help to minimize the incidence of herniation recurrence and need for revisional surgery.

In vitro and in vivo applications of a universal and synthetic thermo-responsive drug delivery hydrogel platform

A synthetic and thermo-responsive polymer, poly(N-isopropylacrylamide)-co-(polylactide/2-hydroxy methacrylate)-co-(oligo (ethylene glycol)), is used to formulate a universal carrier platform for sustained drug release. The enabling carrier, denoted as TP, is prepared by dissolving the polymer in an aqueous solution at a relatively neutral pH. A wide range of therapeutic moieties can be incorporated without the need for the addition of surfactants, organic solvents, and other reagents to the carrier system. The resulting solution is flowable through fine gauge needle, allowing accurate administration of TP to the target site. After injection, TP carrier undergoes a coil to globe phase transition to form a hydrogel matrix at the site. The benign nature of the polymer carrier and its physical gelation process are essential to preserve the biological activity of the encapsulated compounds while the adhesive hydrogel nature of the matrix allows sustained elusion and controlled delivery of the incorporated therapeutics. The TP carrier system has been shown to be non-toxic and elicits a minimal inflammatory response in multiple in vitro studies. These findings suggest the suitability of TP as an enabling carrier of therapeutics for localized and sustained drug delivery. To confirm this hypothesis, the capabilities of TP to encapsulate and effectively deliver multiple therapeutics of different physicochemical characteristics was evaluated. Specifically, a broad range of compounds were tested, including ciprofloxacin HCl, tumor necrosis factor-alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), and recombinant human bone morphogenetic protein 2 (BMP2). In vitro studies confirmed that TP carrier is able to control the release of the encapsulated drugs over an extended period of time and mitigate their burst release regardless of the compounds’ physiochemical properties for the majority of the loaded therapeutics. Importantly, in vitro and in vivo animal studies showed that the released drugs from the TP hydrogel matrix remained potent and bioactive, confirming the high potential of the TP polymer system as an enabling carrier.

Quantifying the Immune Response to a Tissue-Engineered Porcine Extracellular Matrix

Aim: Structural valvular deterioration of xenogenic heart valve replacements is thought to be due to a chronic immune response. We sought to engineer porcine extracellular matrixthat elicits minimal inflammatory immune response. Materials & methods: Whole blood, bone marrowand pericardium were collected from patients undergoing elective cardiac surgery. Porcine extracellular matrix was decellularized, reseeded with homologous mesenchymal stem cellsand exposed to whole blood. Results: DAPI stain confirmed the absence of cells after decellularization, and presence of mesenchymal stem cells after recellularization. There was a significant reduction in IL-1β and TNF-α production in the recellularized matrix. Conclusion: Recellularization of porcine matrix is successful at attenuating the xenogenic immune response and may provide a suitable scaffold to address the current limitations of prosthetic heart valve replacements.

Clinical Application of a Synthetic Hybrid-Scale Fiber Matrix in a Pediatric Trauma Patient

Introduction. Large soft tissue defects resulting from trauma in the pediatric population are common. MLLs are a rare subset of these injuries with no standard treatment regimen. Thorough surgical debridement of these lesions is often warranted to remove necrotic tissue and contamination, which results in a large, open soft tissue defect. STSGs may be used to provide tissue coverage; however, they have limitations, including donor site morbidity and additional surgical time and cost. Case Report. A 12-year-old female with a cutaneous thermal contact burn and an MLL of the right lower medial thigh declined STSG to avoid additional operations. The wound was treated with an SHSFM that is engineered to mimic the structure and architecture of human extracellular matrix and supports cellular infiltration and proliferation with minimal inflammatory response. Over a 4-month period, the SHSFM was applied 6 times at 2- to 3-week intervals, resulting in complete regranulation and wound closure with no further surgical procedures required. Conclusions. This case demonstrates the utility of the SHSFM in the management of pediatric surgical wounds and highlights the flexibility of the SHSFM in achieving the goals of both patient and physician alike.

Endosomal Escapable and Nuclear Localizing Cationic Polyaspartate-Based CRISPR Activation System for Preventing Respiratory Virus Infection by Specifically Inducing Interferon-λ.

Global pandemics caused by viruses cause widespread panic and economic losses. The lack of specific antivirals and vaccines increases the spreading of viral diseases worldwide. Thus, alternative strategies are required to manage viral outbreaks. Here, we develop a CRISPR activation (CRISPRa) system based on polymeric carriers to prevent respiratory virus infection in a mouse model. A polyaspartate grafted with 2-(diisopropylamino) ethylamine (DIP) and nuclear localization signal peptides (NLS-MTAS fusion peptide) was complexed with plasmid DNA (pDNA) encoding dCas9-VPR and sgRNA targeting IFN-λ. The pH-sensitive DIP and NLS-MTAS groups were favor of endo-lysosomal escape and nuclear localization of pDNA, respectively. They synergistically improved gene transfection efficiency, resulting in significant reporter gene expression and IFN-λ upregulation in lung tissue. In vitro and in vivo prophylactic experiments showed that the non-viral CRISPRa system could prevent infection caused by H1N1 viruses with minimal inflammatory responses, presenting a promising prophylactic approach against respiratory virus infections.

Nonwoven Hemostatic Dressings Formed by Contact Drawing of Interposed Polyethylene Oxide (PEO)‐Fibrinogen and PEO‐Thrombin Microfibers

AbstractTextiles containing interposed layers of polyethylene oxide (PEO)‐fibrinogen and PEO‐thrombin fibers are explored as biomaterials for hemostasis. The PEO‐fibrinogen and PEO‐thrombin fibers are formed by contact drawing, an approach that uses an entangled polymer solution and a pin array to form fibers by extension of liquid bridges. The interposition of the PEO‐fibrinogen and PEO‐thrombin fibers results in polymerization of a fibrin hydrogel mesh once the textile is hydrated. This fibrin hydrogel mesh displays the expected bands and diffraction peaks by Fourier‐transform infrared spectromicroscopy and X‐ray diffraction, respectively. The functionality of the hemostatic textiles formed from the interposed PEO‐fibrinogen and PEO‐thrombin fibers is demonstrated by analyzing human blood hemolysis, complement activation, protein adsorption, and platelet and leukocyte adhesion, indicating compatibility with human blood (hemolysis ratio &lt;5%), with minimal inflammatory response (levels of terminal complement complex equivalent to plasma). The cytocompatibility and potential for cell remodeling of the fibrin hydrogel mesh formed by this process is evaluated with human dermal fibroblasts and human keratinocytes and it is found that both cell types attach and grow on the fibrin mesh. Finally, a whole blood clotting time of less than 30 s suggests a potential use of this material in hemorrhage control.

Cytotoxic Activity and Lymphocyte Subtypes in Mice Selected for Maximal and Minimal Inflammatory Response after Transplantation of B16F10 and S91 Melanoma Cells.

AIRmax and AIRmin mice strains were selected according to the intensity of their acute inflammatory responsiveness. Previous studies have shown that AIR mice differ in their resistance to chemically induced skin tumors and in the development of melanoma metastases, in addition to differences in neutrophil and NK cells activity. In the present work, we aimed to evaluate whether the difference of susceptibility to murine melanoma is associated with NK cytotoxic activity against Yac.1 cells and lymphocyte subsets. Mice were subcutaneously inoculated with B16F10 or S91 melanoma cells. After 7, 14, or 30 days, the animals were euthanized to analyze the number of lymphocyte subsets, cytotoxic activity, and number of cytokine-producing spleen cells. AIRmax mice presented a higher number of CD4+/CD25+ cells than that of AIRmin mice following inoculation of B16F10 cells, whereas inoculation of S91 cells reduced CD4+/CD25+ and increased TCD8+ cell subsets in the AIRmax mice. AIRmax mice had a higher number of interleukin (IL)-10- and IL-12-producing cells and a lower number of interferon-γ–producing cells than those of AIRmin mice at 30 days. The cytotoxic activity of nonadherent spleen cells was similar in both the AIR strains. These results suggest that melanoma cells can induce different responses in AIR mice, possibly owing to alterations in regulatory mechanisms, such as the action of CD4+/CD25+ regulatory T cells and IL-10, in AIRmax mice.

Pain and Cellular Migration Induced by Bothrops jararaca Venom in Mice Selected for an Acute Inflammatory Response: Involvement of Mast Cells.

Bothrops jararaca venom (BjV) can induce mast cell degranulation. In order to investigate the role of mast cells and the interference of the host genetic background in the inflammation induced by BjV, we have used mouse strains selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory response (AIR). Mice were pretreated with an inhibitor of mast cell degranulation, cromolyn (CROM), and injected in footpads or intraperitoneally (i.p.) with BjV. Pain was measured with von Frey hairs, cell migration in the peritoneum by flow cytometry, and reactive oxygen species (ROS) production by chemiluminescence assays. The nociceptive response to BjV was higher in AIRmax than AIRmin mice; however, this difference was abolished by pretreatment with CROM. BjV induced peritoneal neutrophil (CD11b+ GR-1+) infiltration and ROS secretion in AIRmax mice only, which were partially inhibited by CROM. Our findings evidence a role for mast cells in pain, neutrophil migration, and ROS production triggered by BjV in AIRmax mice that are more susceptible to the action of BjV.

Mapping of novel loci involved in lung and colon tumor susceptibility by the use of genetically selected mouse strains

Two non-inbred mouse lines, phenotypically selected for maximal (AIRmin) and minimal (AIRmax) acute inflammatory response, show differential susceptibility/resistance to the development of several chemically-induced tumor types. An intercross pedigree of these mice was generated and treated with the chemical carcinogen dimethylhydrazine, which induces lung and intestinal tumors. Genome wide high-density genotyping with the Restriction Site-Associated DNA genotyping (2B-RAD) technique was used to map genetic loci modulating individual genetic susceptibility to both lung and intestinal cancer. Our results evidence new common quantitative trait loci (QTL) for those phenotypes and provide an improved understanding of the relationship between genomic variation and individual genetic predisposition to tumorigenesis in different organs.

Kalsium Sulfat sebagai Bone Graft

Calcium sulfate, which is also known as gypsum or Plaster of Paris has been used widely for more than a century. The use of calcium sulfate is not limited only to industry or food, but also to medicine and dentistry. Furthermore, calcium sulfate can be used as a bone graft for bone regeneration after tooth extraction or other bone loss cases. The development of calcium sulfate has attracted much attention from researchers due to its full biodegradability in bone defects, stimulatory effect on angiogenesis, minimal inflammatory responses, and low cost of production. This article reviews the use of calcium sulfate as a bone graft in medicine and dentistry as well as the advantages and the disadvantages.

Engineered Bacteria Enhance Immunotherapy and Targeted Therapy through Stromal Remodeling of Tumors.

Desmoplastic solid tumors are characterized by the rapid build-up of extracellular matrix (ECM) macromolecules, such as hyaluronic acid (HA). The resulting physiological barrier prevents the infiltration of immune cells and also impedes the delivery of anticancer agents. The development of a hypervesiculating Escherichia coli Nissle (ΔECHy) based tumor targeting bacterial system capable of distributing a fusion peptide, cytolysin A (ClyA)-hyaluronidase (Hy) via outer membrane vesicles (OMVs) is reported. The capability of targeting hypoxic tumors, manufacturing recombinant proteins in situ and the added advantage of an on-site OMV based distribution system makes the engineered bacterial vector a unique candidate for peptide delivery. The HA degrading potential of Hy for stromal modulation is combined with the cytolytic activity of ClyA followed by testing it within syngeneic cancer models. ΔECHy is combined with immune checkpoint antibodies and tyrosine kinase inhibitors (TKIs) to demonstrate that remodeling the tumor stroma results in the improvement of immunotherapy outcomes and enhancing the efficacy of biological signaling inhibitors. The biocompatibility of ΔECHy is also investigated to show that the engineered bacteria are effectively cleared, elicit minimal inflammatory and immune responses, and therefore could be a reliable candidate as a live biotherapeutic.

Successful Utilization of Poly-4-Hydroxybutyrate Mesh in High Risk, Complex Abdominal Wall Reconstructions with Photo-Microscopic Analysis.

Background: Biosynthetic resorbable mesh offers encouraging alternative for reinforcement in complex hernia repairs. This study evaluated outcomes of P4HB, absorbable polymer scaffold, in high-risk patients undergoing complex abdominal hernia repairs. Materials and Methods: This is a retrospective outcomes analysis of a prospectively kept database. Patient/wound characteristics, perioperative findings, short/mid-term outcomes of our cohort were analyzed. Endpoints included hernia recurrences, wound events and any complications. ACS NSQIP online risk calculator was used for each patient to obtain predicted outcomes as virtual matched control group. We also performed a full-thickness abdominal wall biopsy at 14-months post mesh implantation for histologic evaluation. Results: 28 patients with mean age 57 years and mean BMI 31 were analyzed. 21 patients (75%) had preexisting infections. 20 (71%) of patients had class I wounds per CDC classification at time of surgery. However, 19 of these 20 had wound or deep organ/space infections prior to surgery. Repair types included restoration of Linea Alba with retromuscular mesh placement in 23 patients (82%) with 22 of them requiring additional myofascial release. 5 patients (18%) had only mesh placement. Postoperatively, 11 patients (39%) had complications with zero hernia recurrence and zero mesh explantation at maximum of 42 months of follow up. Conclusion: P4HB can be successfully used in high-risk operative fields with no postoperative mesh explantation, despite serious complications such as infected hematomas. Histologic evaluation of the human tissue, 14-months post-implantation of P4HB confirms mesh presence with surrounding dense collagen scaffold formation and minimal inflammatory response.

Biodegradable polymer hydrogel‐based tissue adhesives: A review

Tissue-adhesive materials are emerging biomaterials with potential applications in wound healing patches, tissue sealants, and haemostat materials. Tissue adhesives based on synthetic polymers generally have good adhesion but are not biodegradable. However, the long-term presence of non-biodegradable adhesives in the body can cause secondary harm to the patient. An ideal tissue adhesive should meet the following requirements: good adhesiveness, biodegradability, low cytotoxicity, and minimal inflammatory response. Natural polymers with inherent biodegradation and biocompatibility show great potentials in biomedical engineering, and the development of tissue adhesives based on natural polymers has become a hot topic in biomaterials science. This review systematically summarises the latest progresses in biodegradable tissue adhesives based on natural polymers, such as chitosan, hyaluronic acid, alginate, gelatin, dextran, and cellulose. Methods for preparing natural polymer tissue adhesives are summarised and their advantages and disadvantages are discussed. Finally, potential trends in the future direction of biodegradable tissue adhesives are discussed.

Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance

Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.

Histopathological analysis of schistosomal appendicitis in Kano North-Western Nigeria

Background: Schistosomiasis is a chronic granulomatous inflammation affecting many organs and systems of the body including the gastrointestinal tract with frequent involvement of the appendix. It presents with clinical diagnostic challenge without biopsy and histopathologic evaluation. The study aims to documents the histopathologic pattern of the appendiceal schistosomiasis in our environment. Material and Methods: A 15-year (2004 to 2018) review of all appendix specimens received in the department of Histopahology, Aminu Kano University Teaching Hospital. Information on age, sex and duration of disease was retrieved from request cards and patient case notes. Cases with histological evidence of Schistosomiasis were selected for the study. Data presented as frequency distribution tables, charts and photomicrographs. Results: Thirty six (36) cases of histopathologically confirmed Schistosomal appendicitis constituting 3.2% of all appendectomy specimen with male to female ratio of 9:1, and peak incidence in the third decade of life. Majority (83.3%) of cases show granuloma formation with either calcified or viable schistosoma ova or both. Only 6 cases show Minimal inflammatory response and calcified schistosoma ova. The most common presentation was recurrent and acute appendicitis. Conclusion: Appendiceal schistosomiasis constitutes 3.2% of appendiceal lesions in our settings, affecting predominantly young male. High index of suspicions is therefore advocated in all cases of acute recurrent abdominal pains to avoid unnecessary surgical trauma. Keywords: Appendix, Schistosoma ova, Pathology.

A New Type of Biological Glue Derived from Fish Swim Bladder: Outstanding Adhesion and Surgical Applications

AbstractMechanical strong adhesives have been widely explored in many technical fields. Therefore, a great deal of efforts has been devoted to the widespread investigation of synthetic adhesives and bioadhesives. Nevertheless, it is a crucial challenge to produce economical and practical protein‐based adhesives with robust adhesion properties for biomedical applications. In this study, the fish swim bladder as raw materials to produce robust adhesives by simple heating‐cooling treatment is utilized. The resulting fish swim bladder glue (FSG) reveals excellent lap shear strength on various hard substrates, especially wood and glass, exceeding many commercial available adhesives and artificial protein‐based adhesives. In addition, FSG also has low cytotoxicity and minimal inflammatory response, which exhibits considerable adhesion on soft tissues. Notably, the biocompatibility and biodegradability together with robust adhesion performance endow FSG the capacity in accelerating the wound healing and skin regeneration. Overall, these studies provide insight into the protein‐based adhesives from natural resources.

Late neointimal volume reduction is observed following biodegradable polymer-based drug eluting stent in porcine model.

BackgroundThe BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3–4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES).MethodsBP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density.ResultsOFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (−0.6 ± 0.5 mm2 vs. 0.00 ± 0.4 mm2, p = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively; p < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3, p = 0.09).ConclusionsWhile both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.

In Vivo Evaluation of the Regenerative Capability of Glycylglycine Ethyl Ester-Substituted Polyphosphazene and Poly(lactic-co-glycolic acid) Blends: A Rabbit Critical-Sized Bone Defect Model.

In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly[(glycine ethylglycinato)75(phenylphenoxy)25]phosphazene (PNGEGPhPh) and poly(lactic-co-glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh-PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study. Radiological and histological analyses demonstrated that PNGEGPhPh-PLGA blends exhibited favorable in vivo biocompatibility and osteoconductivity, as the newly designed matrices allowed new bone formation to occur without adverse immunoreactions. The X-ray images of the blends showed higher levels of radiodensity than that of the pristine PLGA, indicating higher rates of new bone formation and regeneration. Micro-computed tomography quantification revealed that new bone volume fractions were significantly higher for the PNGEGPhPh-PLGA blends than for the PLGA controls after 4 weeks. The new bone volume increased linearly with increasing time points, with the new tissues observed throughout the defect area for the blend and only at the implant site's extremes for the PLGA control. Histologically, the polyphosphazene system appeared to show tissue responses and bone ingrowths superior to PLGA. By the end of the study, the defects with PNGEGPhPh-PLGA scaffolds exhibited evidence of effective bone tissue ingrowth and minimal inflammatory responses. Thus, polyphosphazene-containing biomaterials have excellent translational potential for use in bone regenerative engineering applications.

Recent Advances on Bioprinted Gelatin Methacrylate-Based Hydrogels for Tissue Repair.

Bioprinting of body tissues has gained great attention in recent years due to its unique advantages, including the creation of complex geometries and printing the patient-specific tissues with various drug and cell types. The most momentous part of the bioprinting process is bioink, defined as a mixture of living cells and biomaterials (especially hydrogels). Among different biomaterials, natural polymers are the best choices for hydrogel-based bioinks due to their intrinsic biocompatibility and minimal inflammatory response in body condition. Gelatin methacryloyl (GelMA) hydrogel is one of the high-potential hydrogel-based bioinks due to its easy synthesis with low cost, great biocompatibility, transparent structure that is useful for cell monitoring, photocrosslinkability, and cell viability. Furthermore, the potential of adjusting properties of GelMA due to the synthesis protocol makes it a suitable choice for soft or hard tissues. In this review, different methods for the bioprinting of GelMA-based bioinks, as well as various effective process parameters, are reviewed. Also, several solutions for challenges in the printing of GelMA-based bioinks are discussed, and applications of GelMA-based bioprinted tissues argued as well. Impact statement Bioprinting has been demonstrated as a promising and alternative approach for organ transplantation to develop various types of living tissue. Bioinks, with great biological characteristics similar to the host tissues and rheological/flow features, are the first requirements for the successful bioprinting approach. Gelatin methacryloyl (GelMA) hydrogel is one of the high-potential hydrogel-based bioinks. This review provides a comprehensive look at different methods for the bioprinting of GelMA-based bioinks and applications of GelMA-based bioprinted tissues for tissue repair.

Histological Evaluation of Periradicular Tissue Inflammatory Reactions and Calcified Tissue Formations After Implantation of Experimental Calcium Silicate and Hydroxyapatite Based Nanostructural Cements Into Root Canals of Rabbits Teeth

Abstract The aim of the study was to evaluate inflammatory tissue reactions and the formation of calcified tissue after implantation of experimental nanostructured calcium silicate cement (CS) and hydroxyapatite with calcium silicate cement (HA-CS) into root canals of rabbits’ teeth. The study was conducted on four rabbits of the genus Oryctolagus cuniculus. After instrumentation and irrigation, the root canals of the central incisors were dried and filled with CS, HA-CS and control material (MTA Angelus). The animals were sacrificed after 28 days. After histological preparation and hematoxylin-eosin staining, tissue samples were evaluated for the intensity and extension of inflammatory tissue reaction; continuity, morphology and thickness of the newly formed calcified tissue; and presence of giant cells, materials particles and microorganisms. Kruskal Wallis and Dunn’s post hoc test were used for data analysis (α=0.05). There were no significant differences in the intensity of inflammatory reactions between CS, HA-CS and MTA control. HA-CS showed significantly better results than MTA and CS with respect to continuity of the newly formed calcified tissue (P=0.003 and P=0.010, respectively). Significant differences in thickness of the calcified tissue existed between CS and MTA (P=0.004) and between HA-CS and MTA (P=0.012). Application of CS and HA-CS resulted in minimal inflammatory tissue response, similar to the MTA control. CS and HA-CS were more efficient than MTA in supporting hard tissue formation. The best organized newly formed calcified tissue was seen after HA-CS application.