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Cardiovascular diseases represent one of the leading causes of death worldwide. Despite significant advances in the diagnosis and treatment of these diseases, numerous challenges remain in managing them. One of these challenges is the need for replacements for damaged cardiac tissues that can restore the normal function of the heart. Amniotic membrane, as a biological scaffold with unique properties, has attracted the attention of many researchers in recent years. This membrane, extracted from the human placenta, contains growth factors, cytokines, and other biomolecules that play a crucial role in tissue repair. Its anti-inflammatory, antibacterial, and wound-healing properties have made amniotic membrane a promising option for the treatment of heart diseases. This review article examines the applications of amniotic membrane in cardiovascular diseases. By focusing on the mechanisms of action of this biological scaffold and the results of clinical studies, an attempt will be made to evaluate the potential of using amniotic membrane in the treatment of heart diseases. Additionally, the existing challenges and future prospects in this field will be discussed.

Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds. [ABSTRACT FROM AUTHOR]

Advancements in regenerative medicine have highlighted the potential of decellularized extracellular matrix (ECM) as a scaffold for organ bioengineering. Although the potential of ECM in major organ systems is well-recognized, studies focusing on the angiogenic effects of pancreatic ECM are limited. This study investigates the capabilities of pancreatic ECM, particularly its role in promoting angiogenesis. Using a Triton-X-100 solution, porcine pancreas was successfully decellularized, resulting in a significant reduction in DNA content (97.1% removal) while preserving key pancreatic ECM components. A three-dimensional ECM hydrogel was then created from this decellularized tissue and used for cell culture. Biocompatibility tests demonstrated enhanced adhesion and proliferation of mouse embryonic stem cell-derived endothelial cells (mES-ECs) and human umbilical vein endothelial cells (HUVECs) in this hydrogel compared to conventional scaffolds. The angiogenic potential was evaluated through tube formation assays, wherein the cells showed superior tube formation capabilities in ECM hydrogel compared to rat tail collagen. The RT-PCR analysis further confirmed the upregulation of pro-angiogenic genes in HUVECs cultured within the ECM hydrogel. Specifically, HUVECs cultured in the ECM hydrogel exhibited a significant upregulation in the expression of MMP2, VEGF and PAR-1, compared to those cultured in collagen hydrogel or in a monolayer condition. The identification of ECM proteins, specifically PRSS2 and Decorin, further supports the efficacy of pancreatic ECM hydrogel as an angiogenic scaffold. These findings highlight the therapeutic promise of pancreatic ECM hydrogel as a candidate for vascularized tissue engineering application. [ABSTRACT FROM AUTHOR]

ABSTRACTInfection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.

Human acellular amniotic membrane (HAAM) has emerged as a promising tool in the field of regenerative medicine, particularly for wound healing and tissue regeneration. HAAM provides a natural biological scaffold with low immunogenicity and good anti-infective and anti-scarring results. Despite its potential, the clinic application of HAAM faces challenges, particularly with respect to the preparation methods and its low mechanical strength. This review provides a comprehensive overview of HAAM, covering its preparation, sterilization, preclinical research, and clinical applications. This review also discusses promising decellularization and sterilization methods, such as Supercritical Carbon Dioxide (SC-CO2), and the need for further research into the regenerative mechanisms of HAAM. In addition, we discuss the potential of HAAM as a skin dressing and cell delivery system in preclinical research and clinical applications. Both the safety and effectiveness of HAAM have been validated by extensive research, which provides a robust foundation for its clinical application. [ABSTRACT FROM AUTHOR]

Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds.

An ideal artificial bone implant should have similar mechanical properties and biocompatibility to natural bone, as well as an internal structure that facilitates stomatal penetration. In this work, 3D printing was used to fabricate and investigate artificial bone composites based on HA-ZrO2-PVA. The composites were proportionally configured using zirconia (ZrO2), hydroxyapatite (HA) and polyvinyl alcohol (PVA), where the ZrO2 played a toughening role and PVA solution served as a binder. In order to obtain the optimal 3D printing process parameters for the composites, a theoretical model of the extrusion process of the composites was first established, followed by the optimization of various parameters including the spray head internal diameter, extrusion pressure, extrusion speed, and extrusion line width. The results showed that, at the optimum parameters of a spray head diameter of 0.2 mm, extrusion pressure values ranging from 1–3 bar, a line spacing of 0.8–1.5 mm, and a spray head displacement range of 8–10 mm/s, a better structure of biological bone scaffolds could be obtained. The mechanical tests performed on the scaffolds showed that the elastic modulus of the artificial bone scaffolds reached about 174 MPa, which fulfilled the biomechanical requirements of human bone. According to scanning electron microscope observation of the scaffold sample, the porosity of the scaffold sample was close to 65%, which can well promote the growth of chondrocytes and angiogenesis. In addition, c5.18 chondrocytes were used to verify the biocompatibility of the composite materials, and the cell proliferation was increased by 100% when compared with that of the control group. The results showed that the composite has good biocompatibility. [ABSTRACT FROM AUTHOR]

Dental problems including cavities, periodontitis, apical periodontitis, and pulpitis are among the most cost-consuming burden for both patients and the health care system all over the world. The pathological consequences of these complications importantly lead to tooth loss causing functional and psychological conflictions for patients. The traditional treatment includes removing the impaired tooth or its restoration using hard restorative materials that are supposed to mimic the tissue of enamel or dentine whereas these materials cannot simulate the chemical, biological, or physical characteristics of a natural tooth. Therefore, different daily-progressing methods of tissue engineering (TE) are being propounded as new and promising approaches for managing dentistry conflicts. TE is now considered almost a practical, reproducible, and clinically safe therapy for regenerating different oral and dental tissues including either the whole dental organ or its various anatomical parts. TE necessarily constitutes three angles of stem cell (SC), scaffold, and essential growth factors (GFs). Generally, scaffolds can be made of decellularized scaffolds (usually containing the extra-cellular matrix (ECM) of target organs and tissues) or biologic scaffolds (containing natural polymer). The current study aims to review the studies conducted in the recent decade on decellularized and biological scaffolds and their potential applications in modern regenerative dentistry.

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Objective To develop a novel decellularized extracellular matrix (ECM) bioscaffold derived from human cirrhotic liver tissues and construct a 3-dimensional cell culture system using this bioscaffold material. Methods Clinical samples of cirrhotic liver tissues were collected from patients undergoing liver transplantation for hepatic cirrhosis. The cirrhotic liver tissues were cleansed, cut into small tissue blocks (5 mm×5 mm×5 mm), and agitated in deionized water and detergents to obtain decellularized cirrhotic liver scaffold. Human primary human hepatocytes (PHHs) were seeded into the prepared ECM scaffold and cultured continuously for 9 d. Histological studies of the seeded cells were performed to assess the cell engraftment, and qPCR was used to detect the expression of the liver-specific genes in the cultured cells. Results The cirrhotic liver tissue became transparent after decellularization, and HE staining and scanning electron microscopy showed no residual nuclei in the bioscaffold. Residual DNA identification showed that the scaffold material had a residue DNA level less than 10 ng/mg of the tissue. After 9 d of continuous culture in the ECM scaffold, the PHHs showed good engraftment as shown by HE staining; the results of qPCR showed that the cells cultured in this 3D culture system expressed higher levels of liver-specific genes as compared with the cells in conventional 2D culture. Conclusion We successfully construct decellularized ECM bioscaffold derived from human cirrhotic liver tissues and confirmed the feasibility of 3D cell culture using this new bioscaffold material.

The management of large rotator cuff tears in patients without evidence of glenohumeral arthritis is challenging and controversial. We wished to investigate the viability of Graft Jacket® augmentation and assess the clinical and radiological outcomes in a prospective study with a select cohort of patients. All procedures were performed by a single shoulder surgeon over a three-year period. Inclusion criteria were patients with large cuff tears (size 3–5 cm) not amenable to end-to-end repair. Patients with radiographic evidence of glenohumeral arthritis or cuff tear arthropathy were excluded. Open rotator cuff repair followed by bridging with GraftJacket® Regenerative Tissue Matrix was performed. Outcome was assessed with Constant scores (CS), QuickDash (QD) and Oxford Shoulder scores (OSS) at minimum twenty-two months and ultrasound assessment at nine months post-operatively. Thirteen patients were identified who fit inclusion criteria (one bilateral). No patients were lost to follow up. At final follow-up thirteen shoulders had achieved function range of movement. Mean CS was 83 (range 70–100), mean Quick DASH was 5.4 (range 0–18.2), and mean OSS was 46 (range 41–48). Shoulder ultrasound revealed an intact Graft Jacket® in these patients. One patient had lower functional movement and worse CS (34), QD (34.1) and OSS (25) and ultrasound assessment identified a re-rupture. This study indicates that augmentation of large rotator cuff repairs with a GraftJacket® scaffold is a viable option and has good functional results and sustained viability. Level 4. [ABSTRACT FROM AUTHOR]

With the development of technology, tissue engineering (TE) has been widely applied in the medical field. In recent years, due to its accuracy and the demands of solid freeform fabrication in TE, three-dimensional printing, also known as additive manufacturing (AM), has been applied for biological scaffold fabrication in craniofacial and dental regeneration. In this review, we have compared several types of AM techniques and summarized their advantages and limitations. The range of printable materials used in craniofacial and dental tissue includes all the biomaterials. Thus, basic and clinical studies were discussed in this review to present the application of AM techniques in craniofacial and dental tissue and their advances during these years, which might provide information for further AM studies in craniofacial and dental TE.

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Human amniotic membrane (hAM) is considered as a surgical waste without ethical issue, so it is a highly abundant, cost-effective, and readily available biomaterial. It has biocompatibility, low immunogenicity, adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability), and good cell adhesion. It exerts anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects. It is also a source of growth factors, cytokines, and hAM cells with stem cell properties. This important source for scaffolding material has been widely studied and used in various areas of tissue repair: corneal repair, chronic wound treatment, genital reconstruction, tendon repair, microvascular reconstruction, nerve repair, and intraoral reconstruction. Depending on the targeted application, hAM has been used as a simple scaffold or seeded with various types of cells that are able to grow and differentiate. Thus, this natural biomaterial offers a wide range of applications in TE applications. Here, we review hAM properties as a biocompatible and degradable scaffold. Its use strategies (i.e., alone or combined with cells, cell seeding) and its degradation rate are also presented.

In this study, NBG was successfully achieved through a sol-gel technique, and to further improve its dispersibility, a crylate coupling agent was coupled onto the surface of the NBG. The 3-(Trimethoxysilyl)Propylmethacrylate coupling agent was used to the surface modification of the synthesized NBG by a wet-chemical method in a dynamic inert nitrogen atmosphere. The surface properties of the biomaterials before and after modification were characterized and compared using FTIR and AFM techniques. The characteristic peaks in FTIR spectra indicated that –CH2, –CH3 and C=O groups appeared on the surface of modified NBG, and also, AFM analysis revealed that the dispersibility of surface modified NBG was improved, significantly. The above results proved that the desired groups of 3-(Trimethoxysilyl)Propyl methacrylate had been covalently bonded onto the surface of NBG. Besides, a nanocomposite scaffold was synthesized using the synthesized NBG and polyurethane foam as raw materials. The morphology of pores, porosity contents, compress strength and bioactivity of the scaffold were studied. The results showed that the biological scaffolds for use in bone tissue engineering with the basic requirements (90% porosity and 200-600 μm pore diameter) were successfully prepared. The polymer component had no effect on the relationship between the scaffold pores and bioactivity of bioglass nanoparticles. Improvement of compressive strength and proper bioactivity of the resulted scaffold showed that it is an acceptable candidate for biomaterials applications.

Of all biologic matrices, decellularized extracellular matrix (dECM) has emerged as a promising tool used either alone or when combined with other biologics in the fields of tissue engineering or regenerative medicine – both preclinically and clinically. dECM provides a native cellular environment that combines its unique composition and architecture. It can be widely obtained from native organs of different species after being decellularized and is entitled to provide necessary cues to cells homing. In this review, the superiority of the macro- and micro-architecture of dECM is described as are methods by which these unique characteristics are being harnessed to aid in the repair and regeneration of organs and tissues. Finally, an overview of the state of research regarding the clinical use of different matrices and the common challenges faced in using dECM are provided, with possible solutions to help translate naturally derived dECM matrices into more robust clinical use. Statement of Significance Ideal scaffolds mimic nature and provide an environment recognized by cells as proper. Biologically derived matrices can provide biological cues, such as sites for cell adhesion, in addition to the mechanical support provided by synthetic matrices. Decellularized extracellular matrix is the closest scaffold to nature, combining unique micro- and macro-architectural characteristics with an equally unique complex composition. The decellularization process preserves structural integrity, ensuring an intact vasculature. As this multifunctional structure can also induce cell differentiation and maturation, it could become the gold standard for scaffolds. [ABSTRACT FROM AUTHOR]

Introduction: There have been attempts to alter the prognosis of severe spinal cord injury in different centers, but none of which have reliably altered the outcome. Some trials use stem cells (SCs) that produced widely differing results. We hereby add our experience in our center of a surgical reconstruction of the damaged spinal cord using a mixture of SCs and Platelet-Rich Protein (PRP) with fibrin coated as a biological scaffold. Materials and Methods: Four cases of severely damaged spinal cord have been operated for neurolysis and reconstruction of the spinal cord using SCs and platelet-rich protein (PRP) with fibrin coated harvested from the peripheral circulation of the patient. PRP serves to maintain the position of the SCs. One milliliter suspension contains an average of 2.8 × 106 of autologous hematopoietic SCs. Patients were intraoperatively monitored by somatosensory evoked potential, motor evoked potentials, and delta wave. They are clinically followed postoperatively and electromyogram was repeated every 2 weeks. Magnetic resonance imaging (MRI) was repeated regularly. The patients are followed up for a period between 2 and 3 years. Results: One patient demonstrated motor and objective sensory improvement (P = 0.05), two other patients reported subjective sensory improvement, and the fourth one remained without any improvement (P = 0.1). None of these patients demonstrated any sign of deterioration or complication either on the surgery or on implanting of the SCs. MRI clearly proved that the inserted biological scaffold remained in place of reconstruction. Conclusion: SCs may play a role in restoring spinal cord functions. However, the unsolved problems of the use of SCs and related ethical issues should be addressed. [ABSTRACT FROM AUTHOR]

In this study, NBG was successfully achieved through a sol-gel technique, and to further improve its dispersibility, a crylate coupling agent was coupled onto the surface of the NBG. The 3-(Trimethoxysilyl)Propylmethacrylate coupling agent was used to the surface modification of the synthesized NBG by a wet-chemical method in a dynamic inert nitrogen atmosphere. The surface properties of the biomaterials before and after modification were characterized and compared using FTIR and AFM techniques. The characteristic peaks in FTIR spectra indicated that -CH2, -CH3 and C=O groups appeared on the surface of modified NBG, and also, AFM analysis revealed that the dispersibility of surface modified NBG was improved, significantly. The above results proved that the desired groups of 3-(Trimethoxysilyl)Propyl methacrylate had been covalently bonded onto the surface of NBG. Besides, a nanocomposite scaffold was synthesized using the synthesized NBG and polyurethane foam as raw materials. The morphology of pores, porosity contents, compress strength and bioactivity of the scaffold were studied. The results showed that the biological scaffolds for use in bone tissue engineering with the basic requirements (90% porosity and 200-600 μm pore diameter) were successfully prepared. The polymer component had no effect on the relationship between the scaffold pores and bioactivity of bioglass nanoparticles. Improvement of compressive strength and proper bioactivity of the resulted scaffold showed that it is an acceptable candidate for biomaterials applications. [ABSTRACT FROM AUTHOR]

The development of biologically templated artificial light harvesting antennae and energy transfer devices is a highly active research area with exceptional challenges. Natural energy harvesting complexes have exquisite spectrally- and spatially-tuned systems with high redundancy to maximize their ability to gather, channel, and distribute electromagnetic radiation. Attempting to mimic these highly efficient systems requires at the very least (sub)nanoscale precision in the positioning of light sensitive molecules, the latter of which must also possess carefully selected photophysical properties; in essence, these two fundamental properties must be exploited in a synergistic manner. First, the scaffold must be highly organized, ideally with multiple symmetrical components that are spatially arranged with nanoscale accuracy. Second, the structure must be amenable to chemical modification in order to be (bio)functionalized with the desired light sensitive moieties which have expanded greatly to now include organic dyes, metal chelates, fluorescent proteins, dye-doped and noble metal nanoparticles, photoactive polymers, along with semiconductor quantum dots amongst others. Several families of biological scaffolding molecules offer strong potential to meet these stringent requirements. Recent advances in bionanotechnology have provided the ability to assemble diverse naturally derived scaffolds along with manipulating their properties and this is allowing us to understand the capabilities and limitations of such artificial light-harvesting antennae and devices. The range of scaffold or template materials that have been used varies from highly symmetrical virus capsids to self-assembled biomaterials including nucleic acids and small peptides as well as a range of hybrid inorganic–biological systems. This review surveys the burgeoning field of artificial light-harvesting and energy transfer complexes that utilize biological scaffolds from the perspective of what each has to offer for optimized energy transfer. We highlight each biological scaffold with prominent examples from the literature and discuss some of the benefits and liabilities of each approach. Cumulatively, the available data suggest that DNA is the most versatile biological material currently available, though it has challenges including precise dye placement and subsequent dye performance. We conclude by providing a perspective on how this field will progress in both the short and long term, with a focus on the transition to applications and devices. [ABSTRACT FROM AUTHOR]

We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm² section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals. [ABSTRACT FROM AUTHOR]

Abstract: The present study investigates the potential use of non-catalyzed water-soluble blocked polyurethane prepolymer (PUP) as a bifunctional cross-linker for collagenous scaffolds. The effect of concentration (5, 10, 15 and 20%), time (4, 6, 12 and 24h), medium volume (50, 100, 200 and 300%) and pH (7.4, 8.2, 9 and 10) over stability, microstructure and tensile mechanical behavior of acellular pericardial matrix was studied. The cross-linking index increased up to 81% while the denaturation temperature increased up to 12°C after PUP crosslinking. PUP-treated scaffold resisted the collagenase degradation (0.167±0.14mmol/g of liberated amine groups vs. 598±60mmol/g for non-cross-linked matrix). The collagen fiber network was coated with PUP while viscoelastic properties were altered after cross-linking. The treatment of the pericardial scaffold with PUP allows (i) different densities of cross-linking depending of the process parameters and (ii) tensile properties similar to glutaraldehyde method. [Copyright &y& Elsevier]

Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering. [ABSTRACT FROM AUTHOR]

The article investigates the differences in the morphological properties and proliferation of olfactory ensheathing cells in three- and two-dimensional cultures. The proliferation rate of olfactory ensheathing cells in three-dimensional culture on collagen-heparan sulfate biological scaffolds was higher versus in two-dimensional culture. Also, over half of the olfactory ensheathing cells subcultured in three-dimensional culture displayed a spindly Schwann cell-like morphology.

Centrifugal electrospinning (CES) was developed by integrating the electrospinning (ES) and centrifugal spinning (CS) concepts to produce oriented and diameter-controlled fibrous scaffolds which were then applied to stimulate the behaviour of fibroblast cells. During the fabrication process, polymer concentrations, rotational speeds, operating voltages, and needle sizes were key parameters to affect the diameters of produced fibres. The mathematical model indicated that the centrifugal force with the power of 2 was the main influence in fabricating thinner fibres, followed by electrostatic force with the power of 1. The developed CES technique could fabricate fibres scaffold ranging from 210 ± 50 nm to 2814 ± 96 nm by only applying low operating voltages and rotation speed which were 10 kV and up to 2000 rpm, respectively. Through optimum parameter, random and aligned nanofibrous were fabricated with the diameter being distributed mainly at 200–400 nm. Aligned nanofibrous demonstrated a high degree of orientation when 88% of the nanofibrous varied at 0°–10°. Compared to random structure, aligned nanofibrous presented high tensile strength, which was approximately 4.35 MPa and appropriate flexibility with 73% of elongation break. Aligned nanofibrous exhibited high cell viabilities with a 2.34 absorbance rate at day 14. The fibroblast cells elongated and accelerated in the orientation of the aligned nanofibrous. Results suggest that fibre aligned scaffolds are possible candidates for wound dressing application. [ABSTRACT FROM AUTHOR]

Driven by market demand, many biological and synthetic scaffolds have been developed during the last 15 years. Both positive and negative results have been reported in clinical applications for tendon and ligament repair. To obtain data for this review, multiple electronic databases were used (e.g., Pubmed and ScienceDirect), as well as the US FDA website and the reference lists from clinical trials, review articles and company reports, in order to identify studies relating to the use of these commercial scaffolds for tendon and ligament repair. The commercial names of each scaffold and the keywords 'tendon' and 'ligament' were used as the search terms. Initially, 378 articles were identified. Of these, 47 were clinical studies and the others were reviews, editorials, commentaries, animal studies or related to applications other than tendons and ligaments. The outcomes were reviewed in 47 reports (six on Restore™, eight on Graftjacket®, four on Zimmer®, one on TissueMend®, five on Gore-Tex®, six on Lars®, 18 on Leeds-Keio® and one study used both Restore and Graftjacket). The advantages, disadvantages and future perspectives regarding the use of commercial scaffolds for tendon and ligament treatment are discussed. Both biological and synthetic scaffolds can cause adverse events such as noninfectious effusion and synovitis, which result in the failure of surgery. Future improvements should focus on both mechanical properties and biocompatibility. Nanoscaffold manufactured using electrospinning technology may provide great improvement in future practice. [ABSTRACT FROM AUTHOR]

Summary: More than a decade after the first reports on successful three-dimensional cardiac cell culture for experimental and potential therapeutic application, the interest and experimental efforts in the field of myocardial tissue engineering continues to grow. The hope that tissue cultures may one day act as graft substitute for malfunctioning myocardium continues to drive current scientific activity. Against this background interest seem to have progressively shifted towards the aim of engineering single tissue components. Accordingly, elements of the extracellular matrix (ECM) have gained increasing attention as potentially crucial mediators in developing and maintaining the characteristics of three-dimensional cardiac cell cultures. The ECM is now no longer regarded as merely a scaffold for developing tissue, a concept that is widely acknowledged in modern tissue engineering. The understanding of the role of precursor and stem cells has highlighted new complicated aspects of cell proliferation and differentiation and ECM proves to play an important role in providing essential signals to influence major intracellular pathways such as proliferation, differentiation and cell metabolism. Furthermore, progress in biochemical engineering has provided the perspective of application of synthetic ECM-linked molecules with bioactive potential. With the advent and continuous refinement of cell removal techniques, a new class of native acellular ECM has emerged with some striking advantages. The presently available ECM materials aim to closely resemble the in vivo microenvironment by acting as an active component of the developing tissue construct. It is therefore not surprising that most of the focus in myocardial tissue engineering has been on cell–matrix interaction, for both naturally derived and synthetic ECM. This article provides a review of established models of myocardial tissue engineering with respect to the employed ECM materials including current frontiers in material development. [Copyright &y& Elsevier]

Understanding of new materials at the molecular level has become increasingly critical for a new generation of nanomaterials for nanotechnology, namely, the design, synthesis and fabrication of nanodevices at the molecular scale. New technology through molecular self-assembly as a fabrication tool will become tremendously important in the coming decades. Basic engineering principles for microfabrication can be learned by understanding the molecular self-assembly phenomena. Self-assembly phenomenon is ubiquitous in nature. The key elements in molecular self-assembly are chemical complementarity and structural compatibility through noncovalent interactions. We have defined the path to understand these principles. Numerous self-assembling systems have been developed ranging from models to the study of protein folding and protein conformational diseases, to molecular electronics, surface engineering, and nanotechnology. Several distinctive types of self-assembling peptide systems have been developed. Type I, “molecular Lego” forms a hydrogel scaffold for tissue engineering; Type II, “molecular switch” as a molecular actuator; Type III, “molecular hook” and “molecular velcro” for surface engineering; Type IV, peptide nanotubes and nanovesicles, or “molecular capsule” for protein and gene deliveries and Type V, “molecular cavity” for biomineralization. These self-assembling peptide systems are simple, versatile and easy to produce. These self-assembly systems represent a significant advance in the molecular engineering for diverse technological innovations. [Copyright &y& Elsevier]

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Human amniotic membrane (hAM) is considered as a surgical waste without ethical issue, so it is a highly abundant, cost-effective, and readily available biomaterial. It has biocompatibility, low immunogenicity, adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability), and good cell adhesion. It exerts anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects. It is also a source of growth factors, cytokines, and hAM cells with stem cell properties. This important source for scaffolding material has been widely studied and used in various areas of tissue repair: corneal repair, chronic wound treatment, genital reconstruction, tendon repair, microvascular reconstruction, nerve repair, and intraoral reconstruction. Depending on the targeted application, hAM has been used as a simple scaffold or seeded with various types of cells that are able to grow and differentiate. Thus, this natural biomaterial offers a wide range of applications in TE applications. Here, we review hAM properties as a biocompatible and degradable scaffold. Its use strategies (i.e., alone or combined with cells, cell seeding) and its degradation rate are also presented. [ABSTRACT FROM AUTHOR]

Skin shares properties of elasticity with muscular tissue. Since elasticity is mostly conferred by muscle cells or elastic fibers, after decellularization the removal of muscle cells causes in decellularized muscles loss of such property, while decellularized skin retains elasticity as skin ECM is rich in elastic fibers that are retained after decellularization. Additionally, mechanic properties are fundamental to ensure myocyte differentiation1 and alignment in myocardium. We developed a fast and efficient protocol of decellularization for human skin using skin fragments from patients undergoing plastic surgery. After decellularization, content of elastin was quantified by quantitative dye-binding method. Additionally elastin content and distribution was evaluated on histological sections by Paraldehyde Fuchsin Gomori and Weigert Van Gieson stainings. Decellularized Human Skin (d-HuSk) obtained was then sectioned into 600um thick sections and used as scaffold to prepare three-dimensional culture of cardiac primitive cells (CPCs). We evaluated, then, CPC survival and ability to differentiate, in vitro, towards cardiomyocytes at gene and protein level when cultured on d-HuSk. Decellularization procedure yielded the acellular extracellular matrix (ECM) with preserved tissue architecture, named d-HuSk. Importantly, histological and quantitative analysis clearly showed the retention of elastic fibers by d-HuSk. CPCs seeded on d-Husk engrafted and survived, and their ability to differentiate towards cardiomyocytes was not lost, as shown by preserved expression of markers specific for cardiac muscle cells, both at protein and gene level. Such results suggest that common signals and properties act both in cardiac and skin microenvironment, making skin a potential powerful and off-the-shelf biological scaffold for cardiovascular regenerative medicine. Although emerging from an in vitro study, the evidence that progenitors of cardiac muscle lineage retain the ability to differentiate on biological scaffold obtained from different, more easily accessible, anatomic site, represents an important advance in cardiovascular regenerative medicine. Specifically, d-HuSk is an alternate biological scaffold that overcomes problems related to the preparation of myocardial biological scaffolds. [ABSTRACT FROM AUTHOR]

Of all biologic matrices, decellularized extracellular matrix (dECM) has emerged as a promising tool used either alone or when combined with other biologics in the fields of tissue engineering or regenerative medicine - both preclinically and clinically. dECM provides a native cellular environment that combines its unique composition and architecture. It can be widely obtained from native organs of different species after being decellularized and is entitled to provide necessary cues to cells homing. In this review, the superiority of the macro- and micro-architecture of dECM is described as are methods by which these unique characteristics are being harnessed to aid in the repair and regeneration of organs and tissues. Finally, an overview of the state of research regarding the clinical use of different matrices and the common challenges faced in using dECM are provided, with possible solutions to help translate naturally derived dECM matrices into more robust clinical use., Statement of Significance: Ideal scaffolds mimic nature and provide an environment recognized by cells as proper. Biologically derived matrices can provide biological cues, such as sites for cell adhesion, in addition to the mechanical support provided by synthetic matrices. Decellularized extracellular matrix is the closest scaffold to nature, combining unique micro- and macro-architectural characteristics with an equally unique complex composition. The decellularization process preserves structural integrity, ensuring an intact vasculature. As this multifunctional structure can also induce cell differentiation and maturation, it could become the gold standard for scaffolds., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells following induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined specific neuronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuronal-specific proteins, including βIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differentiation medium differentiated into a multilayered neural network-like structure with long nerve fibers that was composed of several parallel microfibers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sectioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve.