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Cardiovascular disease such as myocardial infarction is one of the chief reasons for death universally. An extensive variety of natural and synthetic biodegradable polymers have been studied lately for cardiac tissue engineering applications. Cardiac tissue regeneration is a substitute approach for in situ cellular cardiomyoplasties, which is considered to renovate infarcted myocardium utilizing cells, scaffold, and growth factors. Polymer-based scaffolds including graphene and carbon nanotubes can be employed for heart tissue engineering. In this review, we consider the literature in terms of cardiac tissue engineering and discuss the most recent developments in terms of scaffold-based polymers for cardiac tissue regeneration. [ABSTRACT FROM AUTHOR]

The aim of this paper was to evaluate the effect of gel addition to biopolymeric scaffolds on the pro-angiogenic and basic material characteristics of the final composite for use in regenerative medicine. The studied scaffold consisted of natural biopolymers: polyhydroxybutyrate, chitosan, agarose, and gelatin. The final scaffold was characterized by high macroporosity (90%) and wide pore size distribution. As is known, the pore size is a critical factor for cell ingrowth in grafts after implantation in the body and for angiogenic development and creation of new vessels. After 9 days of cultivation in the culture medium, the scaffold retained its physicochemical properties without any tendency of disintegration. The addition of polymeric gels to the scaffold improved the mechanical stability of the composite. In vitro cytotoxicity testing showed good adherence of the seeded L929 fibroblasts on the scaffold and strong ingrowth of cells into the macropores. No sign of cytotoxicity was identified by both the MTS assay and live/dead cell staining. The quail chorioallantoic membrane (CAM) assay—as an alternative to in vivo assays—revealed suitable pro-angiogenic properties of the scaffold for the formation and ingrowth of new blood vessels. Moreover, the upregulation of gene expression responsible for the activation of angiogenic cascade clearly demonstrated a positive effect of the prepared composites on angiogenesis as an essential part of new tissue formation and the regeneration process itself.

Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.

Simple Summary: This study aimed at producing a polymeric scaffold with the ability to replicate the structure and mechanical properties of native trabecular bone. The scaffold's morphological characteristics and mechanical parameters were compared to those of trabecular bone from bovine iliac crest. Using a three-step procedure, the elastic modulus and yield strength were investigated, and a dynamic test was performed to evaluate the mechanical behavior under various loading regimes. The local micromechanics of the scaffolds were assessed with in situ microcomputed tomography and digital volume correlation, which measured the full-field strain distribution. Overall, the results showed that the fabricated polymeric scaffold exhibited mechanical properties in the range of trabecular bone and represents a suitable bone surrogate for in vitro applications, with the potential to be further translated for in vivo clinical purposes. This study presents a polymeric scaffold designed and manufactured to mimic the structure and mechanical compressive characteristics of trabecular bone. The morphological parameters and mechanical behavior of the scaffold were studied and compared with trabecular bone from bovine iliac crest. Its mechanical properties, such as modulus of elasticity and yield strength, were studied under a three-step monotonic compressive test. Results showed that the elastic modulus of the scaffold was 329 MPa, and the one for trabecular bone reached 336 MPa. A stepwise dynamic compressive test was used to assess the behavior of samples under various loading regimes. With microcomputed tomography (µCT), a three-dimensional reconstruction of the samples was obtained, and their porosity was estimated as 80% for the polymeric scaffold and 88% for trabecular bone. The full-field strain distribution of the samples was measured using in situ µCT mechanics and digital volume correlation (DVC). This provided information on the local microdeformation mechanism of the scaffolds when compared to that of the tissue. The comprehensive results illustrate the potential of the fabricated scaffolds as biomechanical templates for in vitro studies. Furthermore, there is potential for extending this structure and fabrication methodology to incorporate suitable biocompatible materials for both in vitro and in vivo clinical applications. [ABSTRACT FROM AUTHOR]

Wound healing is a process getting affected by internal and external factors and might be interrupted by infections. To overcome infections during wound healing, novel antibacterial agents such as antimicrobial peptides have gained popularity because of the rising antibiotic resistance. Therefore, in this study, a three‐dimensional polymeric scaffold was designed for the controlled release of HF‐18 peptide, with the contribution of hyaluronic acid, chondroitin sulfate, and chitosan polymers with the crosslinker genipin. The obtained scaffold structure (OPT) was found to have interconnected pores, was pH‐responsive and swelled more in acidic conditions (5446.5% at pH: 5.0). It was observed that HF‐18‐loaded OPT (P‐OPT) was able to release HF‐18 peptide both in acidic and neutral conditions in a controlled release manner. This study also demonstrated that both OPT and P‐OPT were biocompatible and promoted L929 cell attachment and migration. Antimicrobial activity assessments demonstrated that P‐OPT was effectively bactericidal on Staphylococcus aureus and methicillin‐resistant S. aureus. Moreover, OPT produced a synergistic effect on the antimicrobial activity of HF‐18 peptide, as P‐OPT showed activity below the reported MIC value. As a result, OPT is considered a promising scaffold as a carrier for HF‐18 for wound healing. [ABSTRACT FROM AUTHOR]

Diabetes associated injury healing and other tissue irregularities are viewed as a significant concern. The purpose of the study is to design the wound regeneration activity of Ficus carica extract (FFE) loaded amphiphilic polymeric scaffold of poly(xylitol-g-adipate-co-glutamide) (PXAG)–polyhydroxybutyrate (PHB) for potential diabetic affected wound regeneration. The PXAG copolymer was prepared by the condensation method, and the polymeric scaffolds of PXAG-PHB, PXAG-PHB/FFE were developed through the ultra-sonication process and magnetic stirrer processes. The chemical structure, crystalline nature, thermal stability, size, surface charge and surface morphology of PXAG-PHB and PXAG-PHB/FFE polymeric scaffolds were investigated. The PXAG-PHB/FFE exhibits 99.0% free radical scavenging activity which was determined by the DPPH method. The inhibition zones by the PXAG-PHB/FFE indicate it had a higher antibacterial activity with the Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) pathogens. The PXAG, PXAG-PHB and PXAG-PHB/FFE polymeric scaffolds exhibited good viability against diabetic induced wound cells (WS1) in 100 μg/mL concentrations up to 72 h incubation. Since the synthesized PXAG-PHB/FFE polymeric scaffolds possess excellent thermal stability, bioactivity, biocompatibility and antioxidant activity along with potent antimicrobial activity, they play a potential role in diabetic wound tissue regenerations.

This study aimed to evaluate the influence of formulation and procedure parameters in obtaining thick and continuous chitosan/PVA/glycerol nanofibres to be applied in skin care. For that, the polymers were characterized by nuclear magnetic resonance , Fourier-transform infrared spectroscopy, and size-exclusion chromatography. After this, 96 chitosan/PVA/glycerol nanofibre scaffolds were prepared by electrospinning method, using factorial designs. The independent variables were crude and pure chitosan, 2 brands of PVA, 2 needle gauges, high and low polymer concentration, high and low glycerol concentration, and final solution with and without ultrafiltration. Morphological analysis was performed by scanning electron microscopy, atomic force microscopy, and confocal microscopy. The best sample (NF67) presented an average thickness of 268.3 nm, uniform distribution, and high yield. It was obtained at a 1:3.5 (crude chitosan: PVA with lower molecular weight, but more hydrolysed) ratio and lower glycerol concentration, suggesting that the degree of hydrolysis of the PVA is more important than its molecular weight for obtaining better quality nanofibres and that the glycerol also makes the electrospinning process difficult. Thus, it was possible to choose parameters that provide scaffolds that could be applied as a matrix extracellular-like material in wound healing. • Hydrolysis of PVA is more important than its molecular weight in obtaining nanofibers. • It is possible to obtain nanofibers from chitosan, PVA and glycerol. • Glycerol makes electrospinning of chitosan/poly(vinyl alcohol) more difficult. [ABSTRACT FROM AUTHOR]

Diabetes associated injury healing and other tissue irregularities are viewed as a significant concern. The purpose of the study is to design the wound regeneration activity of Ficus carica extract (FFE) loaded amphiphilic polymeric scaffold of poly(xylitol-g-adipate-co-glutamide) (PXAG)–polyhydroxybutyrate (PHB) for potential diabetic affected wound regeneration. The PXAG copolymer was prepared by the condensation method, and the polymeric scaffolds of PXAG-PHB, PXAG-PHB/FFE were developed through the ultra-sonication process and magnetic stirrer processes. The chemical structure, crystalline nature, thermal stability, size, surface charge and surface morphology of PXAG-PHB and PXAG-PHB/FFE polymeric scaffolds were investigated. The PXAG-PHB/FFE exhibits 99.0% free radical scavenging activity which was determined by the DPPH method. The inhibition zones by the PXAG-PHB/FFE indicate it had a higher antibacterial activity with the Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) pathogens. The PXAG, PXAG-PHB and PXAG-PHB/FFE polymeric scaffolds exhibited good viability against diabetic induced wound cells (WS1) in 100 μg/mL concentrations up to 72 h incubation. Since the synthesized PXAG-PHB/FFE polymeric scaffolds possess excellent thermal stability, bioactivity, biocompatibility and antioxidant activity along with potent antimicrobial activity, they play a potential role in diabetic wound tissue regenerations. [ABSTRACT FROM AUTHOR]

Knee menisci are structurally complex components that preserve appropriate biomechanics of the knee. Meniscal tissue is susceptible to injury and cannot heal spontaneously from most pathologies, especially considering the limited regenerative capacity of the inner avascular region. Conventional clinical treatments span from conservative therapy to meniscus implantation, all with limitations. There have been advances in meniscal tissue engineering and regenerative medicine in terms of potential combinations of polymeric biomaterials, endogenous cells and stimuli, resulting in innovative strategies. Recently, polymeric scaffolds have provided researchers with a powerful instrument to rationally support the requirements for meniscal tissue regeneration, ranging from an ideal architecture to biocompatibility and bioactivity. However, multiple challenges involving the anisotropic structure, sophisticated regenerative process, and challenging healing environment of the meniscus still create barriers to clinical application. Advances in scaffold manufacturing technology, temporal regulation of molecular signaling and investigation of host immunoresponses to scaffolds in tissue engineering provide alternative strategies, and studies have shed light on this field. Accordingly, this review aims to summarize the current polymers used to fabricate meniscal scaffolds and their applications in vivo and in vitro to evaluate their potential utility in meniscal tissue engineering. Recent progress on combinations of two or more types of polymers is described, with a focus on advanced strategies associated with technologies and immune compatibility and tunability. Finally, we discuss the current challenges and future prospects for regenerating injured meniscal tissues.

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy that accounts for the majority of deaths from all thyroid cancers. ATC exhibits invasiveness and highly resistance to conventional therapies which include cytotoxic chemotherapy, the combination of BRAF and MEK inhibition and, more recently, immunotherapies, that have shown promising but still limited results. A growing knowledge on ATC tumor biology is needed for developing more effective therapies with significant better survival. Researchers have begun to utilize 3D models to culture cancer cells for in vitro studies. In this work, C643 ATC cell line was cultured on polymeric scaffolds with high-interconnected porous matrix. They exhibited distinct viability, proliferation and 3D morphology similar to an in vivo solid tumor mass. We also carried out quantitative real-time PCR experiments for monitoring Cancer Stem Cells enrichment, since they are most probably the cause of tumor resistance, reoccurrence and metastasis. The same tests were performed after cell treatment with the chemotherapic Doxorubicin. An up-regulation of the analyzed stem-cell markers confirmed the high resistance to treatment of these cell line with respect to conventional drugs. In conclusion, 3D scaffolds could be an ideal platform for studying the mechanisms that regulate ACT growth and survival and also improving novel therapeutic approaches for treatment-resistant thyroid cancer. • 3D PLLA scaffold resulted as an ideal platform for thyroid cancer cells culture. • Proliferation and morphology of ATC cells grown on scaffold were as like as in vivo. • Cancer stem cells markers resulted up-regulated for cells cultured on scaffolds. • High resistance to therapeutics of ATC was confirmed after Doxorubicin treatment. [ABSTRACT FROM AUTHOR]

Aim: The present work is based on preparation of different grades of Moringa Bark Gum (MOG) with Acrylamide (AM) with varying amount of AM (monomer) and APS (redox initiator) using microwave accelerated free radical reaction. Objectives: In the current work, the Moringa bark gum grafted with acrylamide graft copolymer was tested for tissue engineered polymeric scaffold as well as controlled drug delivery system using metronidazole as a model drug. Methodology: The microwave radiation process was used along with redox initiator for the graft copolymerization process and the optimization of the grades was done using % grafting efficiency, intrinsic viscosity. Moreover, the optimized grade GF4 was analyzed with FTIR as well as NMR proving efficient grafting has resulted along with TGA, OCA and XRD. Results: The grade GF4 showed 95% drug release for 24 hours with only 1% hemolysis proving non-toxic and SEM images evidence its biodegradability thereby making the grade GF4 suitable for controlled release as well as tissue engineered scaffold. Conclusion: The results indicated that the optimized grade GF4 can be utilized as biodegradable polymer having applications in controlled delivery of drugs as well as scaffold for cell proliferation in wound healing and burn therapies. [ABSTRACT FROM AUTHOR]

Conventional transdermal drug delivery systems (TDDS) have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.

In this study, the synergistic effect of graphene oxide (GO) and Montmorillonite (MMT) additives on the chemical, physical, mechanical, and biological properties of chitosan-gelatin (CS-Gel) scaffolds samples were investigated. FT-IR, XRD, Raman spectroscopy, and zeta potential analysis were used to investigate the accuracy of GO synthesis. Morphological studies of scaffold samples showed highly porous structure of all scaffold samples. The water absorption values of CS-Gel/GO and CS-Gel/GO/MMT samples were almost the same, but the highest value of water retention was observed for CS-Gel/GO scaffold. All scaffold samples showed the ability to form biomineral on the surface when exposed to SBF, although CS-Gel/GO/MMT scaffold had the best biomineralization ability. Considerable improvement in mechanical properties of scaffold samples were observed for CS-Gel/GO/MMT in comparison to CS-Gel scaffold, from 17.56 to 22.73 MPa for Young's modulus and from 0.14 to 0.2265 MPa for compressive strength. Protein adsorption of the scaffold was almost doubled in CS-Gel/GO/MMT samples compared to CS-Gel scaffold. Cell viability results indicated that none of the samples were cytotoxic and 30% of improvement in cell viability was observed for CS-Gel/GO/MMT scaffold in comparison to CS-Gel samples after 72 h of incubation. [ABSTRACT FROM AUTHOR]

The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds.

The process of wound healing involves complex interplay of systems biology, dependent on coordination of various cell types, both intra and extracellular mechanisms, proteins, and signaling pathways. To enhance these interactions, drugs must be administered precisely and continuously, effectively regulating the intricate mechanisms involved in the body's response to injury. Controlled drug delivery systems (DDS) play a pivotal role in achieving this objective. A proficient DDS shields the wound from mechanical, oxidative, and enzymatic stress, against bacterial contamination ensuring an adequate oxygen supply while optimizing the localized and sustained delivery of drugs to target tissue. A pH-sensitive SPH was designed by blending two natural polysaccharides, Opuntia mucilage and carrageenan, using microwave irradiation and optimized according to swelling index at pH 1.2, 7.0, and 8.0 and % porosity. Optimized grade was analyzed for surface hydrophilicity-hydrophobicity using OCA. Analytical characterizations were performed using FTIR, TGA, XRD, DSC, reflecting semicrystalline behavior. Mechanical property confirmed adequate strength. In vitro drug release study with ciprofloxacin-HCL as model drug showed 97.8 % release within 10 h, fitting to the Korsmeyer-Peppas model following diffusion and erosion mechanism. In vitro antimicrobial, anti-inflammatory assays, zebrafish toxicity, and animal studies in mice with SPH concluded it as a novel biomaterial. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To assess the in vivo biomechanical maturation of tissue-engineered neo-uteri that have previously supported live births in a rabbit model., Design: Nonclinical animal study., Setting: University-based research laboratory., Animals: Eighteen adult female rabbits., Intervention: Biodegradable poly-DL-lactide-co-glycolide-coated polyglycolic acid scaffolds seeded with autologous uterine-derived endometrial and myometrial cells. Nonseeded scaffolds and seeded, tissue-engineered neo-uteri were implanted into one uterine horn of rabbits for 1, 3, or 6 months, excised, and biomechanically assessed in comparison to native uterine tissue., Main Outcome Measures: Tensile stress-relaxation testing, strain-to-failure testing, and viscoelastic modeling., Results: By evaluating the biomechanical data with several viscoelastic models, it was revealed that tissue-engineered uteri were more mechanically robust than nonseeded scaffolds. For example, the 10% instantaneous stress of the tissue-engineered neo-uteri was 2.1 times higher than the nonseeded scaffolds at the 1-month time point, 1.6 times higher at the 3-month time point, and 1.5 times higher at the 6-month time point. Additionally, as the duration of implantation increased, the engineered constructs became more mechanically robust (e.g., 10% instantaneous stress of the tissue-engineered neo-uteri increased from 22 kPa at 1 month to 42 kPa at 6 months). Compared with native tissue values, tissue-engineered neo-uteri achieved or surpassed native tissue values by the 6-month time point., Conclusion: The present study evaluated the mechanical characteristics of novel tissue-engineered neo-uteri that have previously been reported to support live births in the rabbit model. We demonstrate that the biomechanics of these implants closely resemble those of native tissue, giving further credence to their development as a clinical solution to uterine factor infertility., Competing Interests: Declaration of interests R.C.N. has nothing to disclose. R.S.M. has nothing to disclose. I.C. has nothing to disclose. J.K.W. has nothing to disclose. A.A. has reported that Boston Children’s Hospital was assigned the rights to two issued patents, both titled “Tissue Engineered Uterus,” no. 7,049,057, filed November 15, 2002, and no. 7,429,490, filed February 7, 2005, with A.A. listed as an inventor. On the basis of the remaining patent term and the need for further studies before this technology is used clinically, there are no current or expected financial interests related to these patents. E.G.L. has nothing to disclose., (Published by Elsevier Inc.)

Graphical abstract Abstract Bone infection is a devastating condition resulting from implant or orthopaedic surgery. Therapeutic strategies are extremely complicated and may result in serious side effects or disabilities. The development of enhanced 3D scaffolds, able to promote efficient bone regeneration, combined with targeted antibiotic release to prevent bacterial colonization, is a promising tool for the successful repair of bone defects. Herein, polymeric electrospun scaffolds composed of polycaprolactone (PCL) nanofibres decorated with poly(lactic-co-glycolic acid) (PLGA) particles loaded with rifampicin were fabricated to achieve local and sustained drug release for more efficient prevention and treatment of infection. The release profile showed an initial burst of rifampicin in the first six hours, enabling complete elimination of bacteria. Sustained and long-term release was observed until the end of the experiments (28 days), facilitating a prolonged effect on the inhibition of bacterial growth, which is in agreement with the common knowledge concerning the acidic degradation of the microparticles. In addition, bactericidal effects against gram negative (Escherichia coli) and gram positive (Staphylococcus aureus) bacteria were demonstrated at concentrations of released rifampicin up to 58 ppm after 24 h, with greater efficacy against S. aureus (13 ppm vs 58 ppm for E. coli). Cell morphology and cytocompatibility studies highlighted the suitability of the fabricated scaffolds to support cell growth, as well as their promising clinical application for bone regeneration combined with prevention or treatment of bacterial infection. [ABSTRACT FROM AUTHOR]

Abstract Polymeric composite scaffold renders great potential in the remodeling of the damaged tissues when compared to the traditional materials such as autograft, allograft and xenograft. Recently, polymeric scaffolds fabricated using the electrospinning technique has been widely utilized in regenerative medicine. In this study, a novel electrospun composite scaffold based on polyurethane (PU) impregnated with MgO nanoparticles (MgO Np) and neem oil was fabricated and their physico-chemical properties were investigated. The fabricated nanocomposites showed reduced fiber and pore diameter than the pristine PU. The incorporation of neem oil and MgO resulted in the decrease in wettability behavior indicating the hydrophobic nature. Differential thermogravimetry (DTG) study revealed the reduced weight loss of the PU membrane with the addition of MgO Np and neem oil. Moreover, the incorporation of MgO Np and neem oil content altered the crystallinity behavior of the PU membrane as depicted in the X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) analysis. Finally, the existence of MgO Np and neem oil facilitated the decrease in the surface roughness and increase in tensile strength of the pristine PU. Hence, this novel nanocomposites exhibiting enhanced physico-chemical properties warrant them as a putative candidate for the regenerative application. Highlights 1) Electrospun polyurethane composite incorporated with MgO and neem oil was fabricated; 2) Morphology, wettability and roughness indicated its superiority than pristine PU; 3) The addition of MgO and neem oil in PU induced a change in crystalline behavior; 4) Thermal analysis depicted a reduced weight loss of the fabricated composites than PU; 5) Improved properties of the composites may be conducive for regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract The evolution of micro and nanofabrication approaches significantly spurred the advancements of cardiac tissue engineering over the last decades. Engineering in the micro and nanoscale allows for the rebuilding of heart tissues using cardiomyocytes. The breakthrough of human induced pluripotent stem cells expanded this field rendering the development of human tissues from adult cells possible, thus avoiding the ethical issues of the usage of embryonic stem cells but also creating patient-specific human engineered tissues. In the case of the heart, the combination of cardiomyocytes derived from human induced pluripotent stem cells and micro/nano engineering devices gave rise to new therapeutic approaches of cardiac diseases. In this review, we survey the micro and nanofabrication methods used for cardiac tissue engineering, ranging from clean room-based patterning (such as photolithography and plasma etching) to electrospinning and additive manufacturing. Subsequently, we report on the main approaches of microfluidics for cardiac culture systems, the so-called "Heart on a Chip", and we assess their efficacy for future development of cardiac disease modeling and drug screening platforms. Highlights • Overview of micro/nanofabrication methods for cardiac tissue engineering. • Clean room-based patterning, electrospinning and additive manufacturing. • Microfluidic technologies for creating disease models and drug screening systems. • Electrical and mechanical stimulation of cardiac cells on chip. • Micro-engineered "Human Heart on a Chip". [ABSTRACT FROM AUTHOR]

Hypothesis The development of novel scaffolds based on biocompatible polymers is of great interest in the field of bone repair for fabrication of biodegradable scaffolds that mimic the extracellular matrix and have osteoconductive and osteoinductive properties for enhanced bone regeneration. Experiments Polycaprolactone (PCL) and polycaprolactone/polyvinyl acetate (PCL/PVAc) core–shell fibers were synthesised and decorated with poly(lactic- co -glycolic acid) [PLGA] particles loaded with bone morphogenetic protein 2 (BMP2) by simultaneous electrospinning and electrospraying. Hydroxyapatite nanorods (HAn) were loaded into the core of fibers. The obtained scaffolds were characterised by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The in vitro potential of these materials for bone regeneration was assessed in biodegradation assays, osteoblast viability assays, and analyses of expression of specific bone markers, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Findings PLGA particles were homogeneously distributed in the entire fibre mat. The growth factor load was 1.2–1.7 μg/g of the scaffold whereas the HAn load was in the 8.8–12.6 wt% range. These scaffolds were able to support and enhance cell growth and proliferation facilitating the expression of osteogenic and osteoconductive markers (OCN and OPN). These observations underline the great importance of the presence of BMP2 in scaffolds for bone remodelling as well as the good potential of the newly developed scaffolds for clinical use in tissue engineering. [ABSTRACT FROM AUTHOR]

Gene delivery is a potent alternative in comparison with angiogenic growth factor delivery to stimulate the growth of new blood vessels in tissue constructs. The combining of polymeric scaffolds with gene delivery is a promising strategy to achieve controlled, localized, and sustained release of vectors carrying genes encoding angiogenic growth factors (GF) into the target site. This can overcome the limitations of both direct delivery of growth factors and genes encoding them. Recently, various gene delivery based strategies have been used to improve angiogenesis. In this regard, surveying and discussing these studies along with their theoretical principals is required for the full understanding and exploring the great potential of this approach. To this aim, we have provided an illustrated and comprehensive review, which first explains the basic principles of the vascularization in the body and then the importance of the vascularization in tissue engineering. This has been followed by a systematic survey of gene delivery methods, the mechanism of gene uptake by cells and polymeric carrier preparation and loading methods. It can be concluded that in spite of some promising results, gene delivery based angiogenesis is still in its infancy, requiring further investigations to explore the potential of this strategy. [ABSTRACT FROM PUBLISHER]

Conventional transdermal drug delivery systems (TDDS) have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches. [ABSTRACT FROM AUTHOR]

Bone regeneration requires scaffolds with a suitable nanostructured 3D-network and decorated with bioactive functionalities to promote cell ingrowth and induce the intended biological responses. In this work, highly porous poly(ε-caprolactone) (PCL) scaffolds containing biodegradable mesoporous microparticles (starch aerogel microspheres) and a bioactive compound (ketoprofen, a NSAID) were designed and produced using supercritical technologies (scCO 2 impregnation/deposition and foaming) for bone regeneration purposes. One-micron-sized starch aerogel microspheres were processed for the first time. The effects of the incorporation of aerogel powders in the synthetic PCL-based scaffolds on the morphological, physico-chemical and mechanical properties of the construct were evaluated by N 2 adsorption-desorption analysis, scanning electron microscopy, mercury intrusion porosimetry, 3D-modeling, dynamic mechanical analysis and differential scanning calorimetry methods. Scaffolds containing starch aerogels presented an increased porosity and pore interconnectivity to promote the bone tissue growth processes at the expense of a minor decrease in the mechanical properties. The scaffolds showed sustained release of ketoprofen (37 °C, pH 7.4) in the timeframe of days with faster release rate in the case of scaffolds containing starch aerogels. Therefore, scaffolds containing starch aerogel microspheres and obtained by supercritical foaming are an attractive solution to obtain drug-loaded scaffolds with accurate pore structure (porosity, pore size distribution, interconnectivity) for cell in-growth and with sustained release profiles of bioactive compounds. [ABSTRACT FROM AUTHOR]

Polymers are amongst the main candidate materials for load bearing tissue engineering scaffolds. Their effective and reliable clinical uses necessitate insightful analyses of the nonlinear characteristics, which has so far received little attention in literature. To better understand the failure characteristics of these porous structures, yielding behaviors of scaffolds made of a commercial photopolymer (RGD720) were studied using experiments and finite element method (FEM). The polymer exhibits substantial softening under uniaxial material test, but the extent of such softening behavior in a scaffold structure is compromised or even eliminated due to the internal non-uniformity of material yielding. [ABSTRACT FROM AUTHOR]

The degree of stent/scaffold embedment could be a surrogate parameter of the vessel wall-stent/scaffold interaction and could have biological implications in the vascular response. We have developed a new specific software for the quantitative evaluation of embedment of struts by optical coherence tomography (OCT). In the present study, we described the algorithm of the embedment analysis and its reproducibility. The degree of embedment was evaluated as the ratio of the embedded part versus the whole strut height and subdivided into quartiles. The agreement and the inter- and intra-observer reproducibility were evaluated using the kappa and the interclass correlation coefficient (ICC). A total of 4 pullbacks of OCT images in 4 randomly selected coronary lesions with 3.0 × 18 mm devices [2 lesions with Absorb BVS and 2 lesions with XIENCE (both from Abbott Vascular, Santa Clara, CA, USA)] from Absorb Japan trial were evaluated by two investigators with QCU-CMS software version 4.69 (Leiden University Medical Center, Leiden, The Netherlands). Finally, 1481 polymeric struts in 174 cross-sections and 1415 metallic struts in 161 cross-sections were analyzed. Inter- and intra-observer reproducibility of quantitative measurements of embedment ratio and categorical assessment of embedment in Absorb BVS and XIENCE had excellent agreement with ICC ranging from 0.958 to 0.999 and kappa ranging from 0.850 to 0.980. The newly developed embedment software showed excellent reproducibility. Computer-assisted embedment analysis could be a feasible tool to assess the strut penetration into the vessel wall that could be a surrogate of acute injury caused by implantation of devices. [ABSTRACT FROM AUTHOR]

Synthetic polymeric scaffolds to be used as surrogates of autologous bone grafts should not only have suitable physicochemical and mechanical properties, but also contain bioactive agents such as growth factors (GFs) to facilitate the tissue growth. For this purpose, cost-effective and autologous GFs sources are preferred to avoid some post-surgery complications after implantation, like immunogenicity or disease transmission, and the scaffolds should be processed using methods able to preserve GFs activity. In this work, poly(ɛ-caprolactone) (PCL) scaffolds incorporating GFs were processed using a green foaming process based on supercritical fluid technology. Preparation rich in growth factors (PRGF), a natural and highly available cocktail of GFs obtained from platelet rich plasma (PRP), was used as GF source. PCL:starch:PRGF (85:10:5 weight ratio) porous solid scaffolds were obtained by a supercritical CO 2 -assisted foaming process at 100 bar and 37 °C with no need of post-processing steps. Bioactivity of GFs after processing and scaffold cytocompatibility were confirmed using mesenchymal stem cells. The performance of starch as GF control release component was shown to be dependent on starch pre-gelification conditions. [ABSTRACT FROM AUTHOR]

This study reports the use of biocompatible and biodegradable polymers for the formulation and design of an implantable multipolymeric drug delivery device (MDDD) for the management of AIDS dementia complex (ADC), a debilitating condition affecting the cognitive, motor and behavioral systems in HIV+ individuals. A 3-factor Box-Behnken statistical design was employed for the optimization of nanoparticle and multipolymeric scaffold formulations. Fifteen formulations were generated using the Box-Behnken template, which were assessed for physicochemical and physicomechanical characterization. The optimised nanoparticle formulation yielded nanoparticles measuring 68.04 nm in size and zeta potential (ZP) of −13.4 mV was calculated for the colloidal system. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a multipolymeric matrix. Matrix erosion was calculated at 28% for multipolymeric scaffold and a matrix resilience of 4.451% was observed 30 days post exposure to PBS, indicating slow degradation of the MDDD. In vivo studies showed 12.793 ng/mL and 35.225 ng/mL AZT level in plasma and CSF. In view of the physicomechanical properties, in vitro and in vivo drug release kinetics of MDDD makes it a potential candidate for the management of the ADC. [ABSTRACT FROM AUTHOR]

Interaction of endothelial-lineage cells with three-dimensional substrates was much less studied than that with flat culture surfaces. We investigated the in vitro attachment of both mature endothelial cells (ECs) and of less differentiated EC colony-forming cells to poly-ε-capro-lactone (PCL) fibers with diameters in 5–20 μm range ('scaffold microfibers', SMFs). We found that notwithstanding the poor intrinsic adhesiveness to PCL, both cell types completely wrapped the SMFs after long-term cultivation, thus attaining a cylindrical morphology. In this system, both EC types grew vigorously for more than a week and became increasingly more differentiated, as shown by multiplexed gene expression. Three-dimensional reconstructions from multiphoton confocal microscopy images using custom software showed that the filamentous (F) actin bundles took a conspicuous ring-like organization around the SMFs. Unlike the classical F-actin-containing stress fibers, these rings were not associated with either focal adhesions or intermediate filaments. We also demonstrated that plasma membrane boundaries adjacent to these circular cytoskeletal structures were tightly yet dynamically apposed to the SMFs, for which reason we suggest to call them ‘actin grips’. In conclusion, we describe a particular form of F-actin assembly with relevance for cytoskeletal organization in response to biomaterials, for endothelial-specific cell behavior in vitro and in vivo , and for tissue engineering. [ABSTRACT FROM AUTHOR]

Tissue-engineered oral mucosa, in the form of epithelial cell sheets or full-thickness oral mucosa equivalents, is a potential solution for many patients with congenital defects or with tissue loss due to diseases or tumor excision following a craniofacial cancer diagnosis. In the laboratory, it further serves as an in vitro model, alternative to in vivo testing of oral care products, and provides insight into the behavior of the oral mucosal cells in healthy and pathological tissues. This review covers the old and new generation scaffold types and materials used in oral mucosa engineering; discusses similarities and differences between oral mucosa and skin, the methods developed to reconstruct oral mucosal defects; and ends with future perspectives on oral mucosa engineering. [ABSTRACT FROM AUTHOR]

Objective: In this study, polymeric hydrogels were prepared which contain peptides for reducing neuroinflammation and selectively triggering nerve cell adhesion. These peptides were immobilized to polymeric structures using different conjugation methods. Hydrogels are biocompatible and biodegradable polymeric scaffolds, and hydrogels containing bioactive molecules can also be used as effective and controlled drug release platforms by using properties such as adjustable physical strength, porosity, biodegradability and high water holding capacity. Methods: General cell adhesion peptide RGD and the neuron-specific cell adhesion peptide IKVAV were conjugated to a hydrogel structure. Using thiol-in click chemistry, synthetic and hydrophilic PEG-based hydrogel structures reinforced with Poly (lactic acid) (PLA) (5-10-20% wt) and Hyaluronic acid (HA) (10-20-30% wt) polymers and its suitability for mechanical nerve cell attachment were evaluated. On the other hand, HA-MA with methacrylate functional groups was prepared at 3% w/v and gelled under UV (365 nm) with photoinitiator. The IKVAV peptide, with a methacrylic group via heterofunctional molecule, was also added. Results: Hydrogels were chemically characterized by FT-IR Spectroscopy and mechanical properties using rheometer. SEM demonstrated that hydrogels have porous structure (30-40 μm). BCA assay and SEM-EDS detector were used for peptide quantitation and ~35% immobilization efficiency was calculated. Using LC-MS/MS, hydrogels were shown to release drug molecules encapsulated within a week slowly. in vitro studies demonstrated non-toxic behavior (>80% viability) of the hydrogels against mouse fibroblast cells. In addition, human brain cortical neuron cells were used on the surface of peptide and non-peptide hydrogels for ongoing cell adhesion studies. Conclusion: Ibuprofen, for reducing neuroinflammation in nerve cell damage, was physically loaded with maximum loading efficiency of 90%, and shown to release in a controlled fashion for at least 1 week. These hydrogels were made selective to nerve cells by the addition of IKVAV. [ABSTRACT FROM AUTHOR]