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Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.

Peripheral nerve and spinal cord injuries are potentially devastating traumatic conditions with major consequences for patients' lives. Severe cases of these conditions are currently incurable. In both the peripheral nerves and the spinal cord, disruption and degeneration of axons is the main cause of neurological deficits. Biomaterials offer experimental solutions to improve these conditions. They can be engineered as scaffolds that mimic the nerve tissue extracellular matrix and, upon implantation, encourage axonal regeneration. Furthermore, biomaterial scaffolds can be designed to deliver therapeutic agents to the lesion site. This article presents the principles and recent advances in the use of biomaterials for axonal regeneration and nervous system repair.

Background: A significant challenge facing tissue engineering is the fabrication of vasculature constructs which contains vascularized tissue constructs to recapitulate viable, complex and functional organs or tissues, and free-standing vascular structures potentially providing clinical applications in the future. Three-dimensional (3D) bioprinting has emerged as a promising technology, possessing a number of merits that other conventional biofabrication methods do not have. Over the last decade, 3D bioprinting has contributed a variety of techniques and strategies to generate both vascularized tissue constructs and free-standing vascular structures., Results: This review focuses on different strategies to print two kinds of vasculature constructs, namely vascularized tissue constructs and vessel-like tubular structures, highlighting the feasibility and shortcoming of the current methods for vasculature constructs fabrication. Generally, both direct printing and indirect printing can be employed in vascularized tissue engineering. Direct printing allows for structural fabrication with synchronous cell seeding, while indirect printing is more effective in generating complex architecture. During the fabrication process, 3D bioprinting techniques including extrusion bioprinting, inkjet bioprinting and light-assisted bioprinting should be selectively implemented to exert advantages and obtain the desirable tissue structure. Also, appropriate cells and biomaterials matter a lot to match various bioprinting techniques and thus achieve successful fabrication of specific vasculature constructs., Conclusion: The 3D bioprinting has been developed to help provide various fabrication techniques, devoting to producing structurally stable, physiologically relevant, and biologically appealing constructs. However, although the optimization of biomaterials and innovation of printing strategies may improve the fabricated vessel-like structures, 3D bioprinting is still in the infant period and has a great gap between in vitro trials and in vivo applications. The article reviews the present achievement of 3D bioprinting in generating vasculature constructs and also provides perspectives on future directions of advanced vasculature constructs fabrication., (© 2021 American Association for Anatomy.)

Biomaterials derived from natural resources have increasingly been used for versatile applications in the central nervous system (CNS). Thanks to their biocompatibility and biodegradability, natural biomaterials offer vast possibilities for future clinical repair strategies for the CNS. These materials can be used for diverse applications such as hydrogels to fill the tissue cavities, microparticles to deliver drugs across the blood-brain barrier, and scaffolds to transplant stem cells. In this review, various uses of prominent protein and polysaccharide biomaterials, with a special focus on collagen, in repair and regenerative applications for the brain are summarized together with their individual advantages and disadvantages., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Various gynecologic diseases and chemoradiation or surgery for the management of gynecologic malignancies may damage the uterus and ovaries, leading to clinical problems such as infertility or early menopause. Embryo or oocyte cryopreservation-the standard method for fertility preservation-is not a feasible option for patients who require urgent treatment because the procedure requires ovarian stimulation for at least several days. Hormone replacement therapy (HRT) for patients diagnosed with premature menopause is contraindicated for patients with estrogen-dependent tumors or a history of thrombosis. Furthermore, these methods cannot restore the function of the uterus and ovaries. Although autologous transplantation of cryopreserved ovarian tissue is being attempted, it may re-introduce malignant cells after cancer treatment. With the recent development in regenerative medicine, research on engineered biomaterials for the restoration of female reproductive organs is being actively conducted. The use of engineered biomaterials is a promising option in the field of reproductive medicine because it can overcome the limitations of current therapies. Here, we review the ideal properties of biomaterials for reproductive tissue engineering and the recent advancements in engineered biomaterials for the regeneration of female reproductive organs.

Numerous biomedical applications imply supportive materials to improve protective, antibacterial, and regenerative abilities upon surgical interventions, oncotherapy, regenerative medicine, and others. With the increasing variability of the possible sources, the materials of natural origin are among the safest and most accessible biomedical tools. Animal, plant, and fungal tissues can further undergo decellularization to improve their biocompatibility. Decellularized scaffolds lack the most reactive cellular material, nuclear and cytoplasmic components, that predominantly trigger immune responses. At the same time, the outstanding initial three-dimensional microarchitecture, biomechanical properties, and general composition of the scaffolds are preserved. These unique features make the scaffolds perfect ready-to-use platforms for various biomedical applications, implying cell growth and functionalization. Decellularized materials can be repopulated with various cells upon request, including epithelial, endothelial, muscle and neuronal cells, and applied for structural and functional biorepair within diverse biological sites, including the skin and musculoskeletal, cardiovascular, and central nervous systems. However, the molecular and cellular mechanisms behind scaffold and host tissue interactions remain not fully understood, which significantly restricts their integration into clinical practice. In this review, we address the essential aspects of decellularization, scaffold preparation techniques, and its biochemical composition and properties, which determine the biocompatibility and immunogenicity of the materials. With the integrated evaluation of the scaffold profile in living systems, decellularized animal, plant, and fungal scaffolds have the potential to become essential instruments for safe and controllable biomedical applications.

Decellularized materials (DMs) are attracting more and more attention because of their native structures, comparatively high bioactivity, low immunogenicity and good biodegradability, which are difficult to be imitated by synthetic materials. Recently, DMs have been demonstrated to possess great potential to overcome the disadvantages of autografts and have become a kind of promising material for tissue engineering. In this systematic review, we aimed to not only provide a quick access for understanding DMs, but also bring new ideas to utilize them more appropriately in tissue engineering. Firstly, the preparation of DMs was introduced. Then, the updated applications of DMs derived from different tissues and organs in tissue engineering were comprehensively summarized. In particular, their advantages, drawbacks and current improvements were emphasized. Moreover, we analyzed and proposed future perspectives.

Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of nonneuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, noncritical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be used, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system., (© 2020 Wiley Periodicals, Inc.)

3D bioprinting directly into injured sites in a surgical setting, intraoperative bioprinting (IOB), is an effective process, in which the defect information can be rapidly acquired and then repaired via bioprinting on a live subject. In patients needing tissue resection, debridement, traumatic reconstruction, or fracture repair, the ability to scan and bioprint immediately following surgical preparation of the defect site has great potential to improve the precision and efficiency of these procedures. In this opinion article, we provide the reader with current major limitations of IOB from engineering and clinical points of view, as well as possibilities of future translation of bioprinting technologies from bench to bedside, and expound our perspectives in the context of IOB of composite and vascularized tissues., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Females are underrepresented in clinical trials evaluating new stent technologies whilst results may differ between the sexes. Females are known to have smaller, more tortuous coronary arteries and have generally more comorbidities. On the other hand, they may have smaller plaque burden. This subgroup-analysis sought to assess sex-specific outcomes after Absorb bioresorbable vascular scaffold (BVS) or XIENCE everolimus-eluting stent (EES) implantation., Methods: The AIDA trial was an investigator-initiated, non-inferiority, all-comers trial, in which 1845 patients were randomly assigned to either Absorb BVS or XIENCE EES. Baseline clinical, angiography and procedural variables, as well as 2-year clinical outcomes were analyzed by sex and device modality., Results: Of the 1845 randomized patients, 475 (25.7%) were females. The 2-year rates of target vessel failure (TVF) with Absorb BVS versus XIENCE EES in females were 6.4% versus 10.6% (HR 0.59; 95% CI: 0.31-1.11; p = 0.10) and in males 12.7% versus 9.7% (HR 1.34; 95% CI: 0.98-1.85; p = 0.07). Males treated with Absorb BVS were at higher risk for TVF compared to females treated with Absorb BVS (HR 2.06; 95% CI 1.21-3.53; p = 0.007). Definite/probable device thrombosis occurred in females with Absorb BVS versus XIENCE EES in 1.6% versus 1.4% (HR 1.15; 95% CI: 0.26-5.12; p = 0.86) and in males 3.9% versus 0.7% (HR 5.55; 95% CI: 2.11-14.35; p < 0.001). A statistical significant interaction between sex and device was present for TVF (p = 0.02), but was not seen for definite/probable device thrombosis (p = 0.08)., Conclusions: In this subgroup analysis, Absorb BVS used in routine practice tends to result in better clinical outcomes in females compared to males., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The shortage of donor organs for transplantation remains a continued problem for patients with irreversible end-stage organ failure. Tissue engineering and regenerative medicine aims to develop therapies to provide viable solutions for these patients. Use of decellularized tissue scaffolds has emerged as an attractive approach to generate tissue constructs that mimic native tissue architecture and vascular networks. The process of decellularization which involves the removal of resident cellular components from donor tissues has been successfully translated to the clinic for applications in patients. However, transplantation of bioengineered solid organs using this approach remains a challenge as the process requires repopulating target cells to achieve functioning organs. This article presents a comprehensive overview of the methods used to achieve decellularization, the types of decellularizing agents, and the potential cell sources that could be used to achieve tissue function. Understanding the mechanism of action of the decellularizing agent and the processing methods will provide the optimal results for applications., (Copyright © 2019. Published by Elsevier Inc.)

Pulmonary disease is a worldwide public health problem that reduces the life quality and increases the need for hospital admissions as well as the risk of premature death. A common problem is the significant shortage of lungs for transplantation as well as patients must also take immunosuppressive drugs for the rest of their lives to keep the immune system from attacking transplanted organs. Recently, a new strategy has been proposed in the cellular engineering of lung tissue as decellularization approaches. The main components for the lung tissue engineering are: (1) A suitable biological or synthetic three-dimensional (3D) scaffold, (2) source of stem cells or cells, (3) growth factors required to drive cell differentiation and proliferation, and (4) bioreactor, a system that supports a 3D composite biologically active. Although a number of synthetic as well biological 3D scaffold suggested for lung tissue engineering, the current favorite scaffold is decellularized extracellular matrix scaffold. There are a large number of commercial and academic made bioreactors, the favor has been, the one easy to sterilize, physiologically stimuli and support active cell growth as well as clinically translational. The challenges would be to develop a functional lung will depend on the endothelialized microvascular network and alveolar-capillary surface area to exchange gas. A critical review of the each components of lung tissue engineering is presented, following an appraisal of the literature in the last 5 years. This is a multibillion dollar industry and consider unmet clinical need., (© 2019 Wiley Periodicals, Inc.)

The development of cellular microenvironments suitable for neural tissue engineering purposes involves a plethora of research fields ranging from cell biology to biochemistry, neurosciences, physics, nanotechnology, mechanobiology. In the last two decades, this multi-disciplinary activity has led to the emergence of numerous strategies to create architectures capable of reproducing the topological, biochemical and mechanical properties of the extracellular matrix present in the central (CNS) and peripheral nervous system (PNS). Some of these approaches have succeeded in inducing the functional recovery of damaged areas in the CNS and the PNS to address the current lack of effective medical treatments for this type of injury. In this review, we analyze recent developments in the realization of two-dimensional and three-dimensional neuronal scaffolds following either top-down or bottom-up approaches. After providing an overview of the different fabrication techniques employed for tailoring the biomaterials, we draw on specific examples to describe the major features of the developed approaches. We then conclude with prospective proof of concept studies on guiding scaffolds and regenerative models on macro-scale brain implants targeting neural regeneration., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Large prospective studies on the use of bioresorbable vascular scaffolds (BVS) for diffuse coronary artery disease are lacking. IT DISAPPEARS is a large multicentre prospective registry investigating the short and long-term outcomes of everolimus-eluting BVS in patients with long coronary lesions and/or multivessel coronary artery disease (ClinicalTrials.gov: NCT02004730). We hereby report the 2-year outcomes of the registry., Methods: We enrolled 1002 patients with complex lesions undergoing implantation of 2040 BVS with a prespecified technique including predilation, correct sizing, and postdilation with non-compliant balloons. The primary endpoint was the rate of device-oriented composite endpoint (DOCE), consisting of cardiac death, target vessel-related myocardial infarction (MI), and ischaemia-driven target lesion revascularization (TLR). Secondary endpoints included: 1) patient-oriented composite endpoint (POCE), consisting of all-cause mortality, all infarctions and all revascularisations; 2) definite/probable scaffold thrombosis., Results: Clinical presentation was an acute coronary syndrome in 59.8% of patients. Total BVS length implanted was 47 ± 22 mm. Postdilation of all scaffolds per patient was performed in 96.8%, while optimal implantation as per study guidelines was applied in 71.4%. Through 2-year follow-up, DOCE occurred in 9.5% of patients (cardiac death 0.6%, target vessel-related MI 5.3%, TLR 6.6%). The rate of POCE was 16.6% and of scaffold thrombosis 1.1%. Female gender, total length of coronary lesions, treatment of bifurcation lesions and use of 2.5 mm scaffolds were independent predictors of DOCE., Conclusions: The 2-year results of IT-DISAPPEARS show that BVS may yield acceptable clinical outcomes in patients with complex coronary lesions when the implantation technique is appropriate., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Neurogenesis and angiogenesis share regulatory factors that contribute to the formation of vascular networks and neuronal circuits in the brain. While crosstalk mechanisms between neural stem cells (NSCs) and the vasculature have been extensively investigated, recent studies have provided evidence that blood vessels also play an essential role in neuronal migration in the brain during development and regeneration. The mechanisms of the neuronal migration along blood vessels, referred to as "vascular-guided migration," are now being elucidated. The vascular endothelial cells secrete soluble factors that attract and promote neuronal migration in collaboration with astrocytes that enwrap the blood vessels. In addition, especially in the adult brain, the blood vessels serve as a migration scaffold for adult-born immature neurons generated in the ventricular-subventricular zone (V-SVZ), a germinal zone surrounding the lateral ventricles. The V-SVZ-derived immature neurons use the vascular scaffold to assist their migration toward an injured area after ischemic stroke, and contribute to neuronal regeneration. Here we review the current knowledge about the role of vasculature in neuronal migration and the molecular mechanisms controlling this process. While most of this research has been done in rodents, a comprehensive understanding of vasculature-guided neuronal migration could contribute to new therapeutic approaches for increasing new neurons in the brain after injury., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Microfracture and scaffold application in the treatment of osteochondral defects is still one of the most frequently used methods in the clinic. The most important step in this treatment method is the stabilization of fibrin clot. Tranexamic acid (TA) is an antifibrinolytic agent commonly used in orthopedic surgery in recent years. This study evaluated the effect of local TA application on healing of experimentally induced osteochondral defects on rabbits., Methods: This paper contains an animal in vivo data and histological outcomes on the effect of TA. Eighteen New Zealand white rabbits were treated unilaterally and cylindrical defects having a width of 4 mm and depth of 5 mm were created in the weight-bearing surfaces of the medial and lateral condyles of the right femur. They were divided into two groups, as group 1 study and group 2 control groups, respectively. One milliliter (ml) of TA was injected into the knee joints of the subjects in group 1. All animals were sacrificed for the extraction of the femur condyles for histologic study at the fourth and eighth weeks after surgery. Histological evaluations were performed by Brittberg and O'Driscoll scores to all samples. Data were organized in a Standard Statistical Package System v.22 software package (SPSS/PC Inc., Chicago, IL.) and reported as mean and median (min-max). Repeated measures ANOVA test was used to compare groups and condyle effects together for each week. p values below 0.05 were considered as statistically significant., Results: Samples were taken in the fourth and eighth weeks. The regularity of the surface in group 1 was smoother, and the tissue stability was more robust. Mean Brittberg scores in both weeks were statistically higher in group 1 when compared with group 2. In the microscopic evaluation, it was observed that the regeneration of subchondral and cartilage tissues were more rapid and organized in group 1, and the mean O' Driscoll scores in both weeks were statistically higher in group 1., Conclusions: Application of TA improves the healing time and tissue stability in osteochondral defects which are implanted a-cellular scaffold after microfracture and should be applicable to humans for the treatment of osteochondral defects.

Osteoarthritis (OA) is a common degenerative disease which involves articular cartilage, and leads to total joint disability in the advanced stages. Due to its avascular and aneural nature, damaged cartilage cannot regenerate itself. Stem cell therapy and tissue engineering represent a promising route in OA therapy, in which cooperation of mesenchymal stem cells (MSCs) and three-dimensional (3D) scaffolds contribute to cartilage regeneration. However, this approach still presents some limits such as poor mechanical properties of the engineered cartilage. The natural dynamic environment of the tissue repair process involves a collaboration of several signals expressed in the biological system in response to injury. For this reason, tissue engineering involving exogenous "influencers" such as mechanostimulation and functional biomolecule delivery systems (BDS), represent a promising innovative approach to improve the regeneration process. BDS provide a controlled release of biomolecules able to interact between them and with the injured tissue. Nano-dimensional BDS is the future hope for the design of personalized scaffolds, able to overcome the delivery problems. MSC-derived extracellular vesicles (EVs) represent an attractive alternative to BDS, due to their innate targeting abilities, immunomodulatory potential and biocompatibility. Future advances in cartilage regeneration should focus on multidisciplinary strategies such as modular assembly strategies, EVs, nanotechnology, 3D biomaterials, BDS, mechanobiology aimed at constructing the functional scaffolds for actively targeted biomolecule delivery. The aim of this review is to run through the different approaches adopted for cartilage regeneration, with a special focus on biomaterials, BDS and EVs explored in terms of their delivery potential, healing capabilities and mechanical features., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Shoulder pain is a common problem in the general population and is responsible for prolonged periods of disability, loss of productivity, absence from work and inability to carry out household activities. Rotator cuff problems account for up to 70% of shoulder pain problems and are the third most prevalent musculoskeletal disorder after those occurring in the lower back and neck. Rotator cuff surgery has high failure rates (25-50% within 12 months), and as a result, there is a pressing need to improve the outcome of rotator cuff surgery. Patch augmented surgery for rotator cuff repairs has recently been developed and is increasingly being used within the UK National Health Service. Patch augmented surgery could lead to a dramatic improvement in patient and surgical outcomes, but its clinical and cost effectiveness needs rigorous evaluation. The existing evidence on the use of patches may be at risk of bias as currently only a small number of single-centre comparative studies appear to have been carried out. Additionally, it is unclear for which patches a clinical study (comparative and non-comparative) has been conducted. This paper outlines the protocol for a systematic review intended to summarise the best available clinical evidence and will indicate what further research is required., Methods: Electronic databases (Medline, Embase and Cochrane) will be systematically searched between April 2006 and the present day for relevant publications using a specified search strategy, which can be adapted for the use in multiple electronic databases, and inclusion criteria. Screening of both titles and abstracts will be done by two independent reviewers with any discrepancies resolved by a third independent reviewer. Data extraction will include information regarding the type of participants, type of intervention and outcomes including but not limited to shoulder-specific function and pain scores, patch-related adverse events and type of study. The results will be summarised in a narrative review where qualitative analysis is not possible., Discussion: This review aims to collate the current evidence base regarding the use of patches to augment rotator cuff repair. The results of this review will help to develop, using consensus methods, the design of a definitive randomised trial assessing the clinical and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and is feasible., Systematic Review Registration: CRD42017057908.

Tissue engineering (TE) and regenerative medicine are progressively developed areas due to many novel tissue replacements and implementation strategies. Increasing knowledge involving the fabrication of biomaterials with advanced physicochemical and biological characteristics, successful isolation and preparation of stem cells, incorporation of growth and differentiation factors, and biomimetic environments gives us a unique opportunity to develop various types of scaffolds for TE. The current strategies for soft tissue reconstitution or regeneration highlight the importance of novel regenerative therapies in cases of significant soft tissue loss and in cases of congenital defects, disease, trauma and ageing. Various types of biomaterials and scaffolds have been tested for soft tissue regeneration. The synthetic types of materials have gained great attention due to high versatility, tunability and easy functionalization for better biocompatibility. This article reviews the current materials that are usually the most used for the fabrication of scaffolds for soft TE; in addition, the types of scaffolds together with examples of their applications for the regenerative purposes of soft tissue, as well as their major physicochemical characteristics regarding the increased applicability of these materials in medicine, are reviewed.

Objectives: The objective of this study was to investigate mid-term clinical outcomes of patients treated with 'full-plastic jacket' (FPJ) everolimus-eluting Absorb bioresorbable vascular scaffold (BRS) implantation., Background: FPJ with BRS may represent an interesting option for patient with diffuse coronary artery disease (CAD), but data on the clinical impact of FPJ using the Absorb BRS are scant., Methods: FPJ was defined as the implantation of >56 mm of overlapping BRS in at least one vessel. We compared outcomes of patients receiving Absorb FPJ vs. non-FPJ within the multicenter prospective RAI Registry., Results: Out of 1505 consecutive patients enrolled in the RAI registry, 1384 were eligible for this analysis. Of these, 143 (10.3%) were treated with BRS FPJ. At a median follow-up of 649 days, no differences were observed between FPJ and non-FPJ groups in terms of the device-oriented composite endpoint (DoCE) (5.6% vs. 4.4%, p = 0.675) or the patient-related composite endpoint (PoCE) (20.9% vs. 15.9%, p = 0.149). Patients receiving FPJ had higher rates of target vessel repeat revascularization (TVR) (11.2% vs. 6.3%, p = 0.042). In the FPJ group, there was no cardiac death and only one (very late) stent thrombosis (ST) (0.7%)., Conclusions: Mid-term outcomes of a FPJ PCI strategy in the setting of diffuse CAD did not show a significant increase in composite device- and patient-related events, with rates of cardiac death and ST comparable to non-FPJ Absorb BRS implantation. However, these findings are hypothesis generating and requiring further validation., (Copyright © 2018. Published by Elsevier B.V.)

Background: The bioresorbable vascular scaffold (BVS) technology may be an appealing option in ST-segment elevation myocardial infarction (STEMI) patients. However, the available evidence on its use in this challenging subset is limited., Methods: Registro Absorb Italiano (RAI) is a multicenter, prospective registry that aims to assess BVS performance through a 5-year follow-up of all consecutive patients who undergone at least 1 successful BVS implantation. As a part of it, a subgroup analysis in STEMI patients was performed and the outcomes of this cohort compared to the remaining population (defined as "non-STEMI") are reported here., Results: Among the 1505 patients enrolled, 317 (21.1%) had STEMI on admission. Among those, 232 (73.2%) underwent primary percutaneous coronary intervention (PCI) within 12 h from symptom onset; 64 (20.2%) were late-comers (>12 h); 16 (5%) underwent PCI after successful thrombolysis while 5 (1.6%) underwent rescue-PCI. At a median follow-up time of 12 months (IQR 6-20 months) no differences were noticed between STEMI and "non-STEMI" groups in terms of device-oriented composite endpoint (4.1% vs. 5.6%; p = 0.3) and its singular components: ischemia-driven target lesion revascularization (3.2% vs. 3.6%; p = 0.7), target-vessel myocardial infarction (3.2% vs. 2.8%; p = 0.7) and cardiac death (0.6% vs. 0.6%; p = 0.9). The rate of definite/probable scaffold thrombosis (ScT) was numerically higher but not significant in the STEMI group (2.5% vs. 1.3%; p = 0.1)., Conclusions: BVS implantation in an unrestricted cohort of STEMI patients is associated with a numerically higher rate of ScT compared to the non-STEMI group. Further studies exploring the potential clinical impact of a pre-specified BVS implantation strategy in this high-risk clinical setting are needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rationale: Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall., Objectives: We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G)., Methods and Results: The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed. There was hardly any difference in curvature between pre-procedure and 12months (-0.0019; p=0.48). The change in angulation from pre- to 12months was negligible (-3.58°; 95% CI [-5.97, -1.20]), but statistically significant. At 6months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of -0.489; p=0.055) and with fibrous volume a positive relationship (estimate of 0.53, p=0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6months (Δ 6months vs. post-proc. is -13.5 [95% CI -14.6, -12.4]) and at 12months (Δ 12months vs. post-proc. is -14.0 [95% CI -15.4, -12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6months and at 12months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6months; thereafter, they remained unchanged., Conclusion: Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12months; importantly, these changes occurred with preservation of the lumen size between 6 and 12months. NCT01960504., (Copyright © 2017. Published by Elsevier B.V.)

Background: Bioresorbable vascular scaffolds (BVS) have been heralded with potential benefits that are especially desired in long lesions, including chronic total occlusions (CTOs). Procedural feasibility and mid-term outcomes of BVS in CTOs have been reported. However, there is still a paucity of data regarding the vascular and healing response to BVS in CTOs evaluated by optical coherence tomography (OCT)., Methods: This study included prospectively 21 patients who had a CTO lesion treated with a BVS. Angiography and OCT scan were recorded at either post-implantation and 1-year follow-up. Quantitative coronary angiography and OCT analyses were performed by an independent core laboratory., Results: The angiographic analysis showed a significant increase in the percentage of in-segment diameter stenosis at 1year (11.89±9.5% vs. 21.84±11.7%; p=0.002). The OCT analysis showed a trend (p=0.07) towards increased mean scaffold area and significant reductions in mean lumen diameter (3.1±0.36mm vs. 2.85±0.47mm; p=0.0046), mean lumen area (7.8±1.73mm 2 vs. 6.76±2mm 2 ; p=0.0082) and minimal lumen area (5.26±1.86mm 2 vs. 3.56±1.52mm 2 ; p<0.0001). Malapposition area and volume decreased from 0.26±0.17mm 2 to 0.08±0.1mm 2 (p=0.0003) and from 14.17±12.92mm 3 to 3.99±4.46mm 3 (p=0.0014), respectively. The rate of uncovered or malapposed struts, measured at the frame level, was 5.29±6.48% at 1year., Conclusions: In a small series of CTO patients treated with BVS implantation, OCT outcomes at 1year displayed an overall favorable vascular response and healing profile., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects., Methods: The relevant articles were searched through PubMed database. The following keywords and search terms were used: "scaffolds," "patient," "clinic," "bone repair," "bone regeneration," "repairing bone defect," "repair of bone," "osteanagenesis," "osteanaphysis," and "osteoanagenesis." The articles were screened according to inclusion and exclusion criteria, performed by two reviewers., Results: A total of 373 articles were obtained using PubMed database. After screening, 20 articles were identified as relevant for the purpose of this systematic review. We collected the data of biological scaffolds and synthetic scaffolds. There are eight clinical studies of biological scaffolds included collagen, gelatin, and cellular scaffolds for bone healing. In addition, 12 clinical studies of synthetic scaffolds on HAp, TCP, bonelike, and their complex scaffolds for repairing bone defects were involved in this systematic review., Conclusions: There are a lot of clinical evidences showed that application of scaffolds had a good ability to facilitate bone repair and osteogenesis. However, the ideal and reliable guidelines are insufficiently applied and the number and quality of studies in this field remain to be improved.

Bioprinting of three-dimensional constructs mimicking natural-like extracellular matrix has revolutionized biomedical technology. Bioprinting technology circumvents various discrepancies associated with current tissue engineering strategies by providing an automated and advanced platform to fabricate various biomaterials through precise deposition of cells and polymers in a premeditated fashion. However, few obstacles associated with development of 3D scaffolds including varied properties of polymers used and viability, controlled distribution, and vascularization, etc. of cells hinder bioprinting of complex structures. Therefore, extensive efforts have been made to explore the potential of various natural polymers (e.g. cellulose, gelatin, alginate, and chitosan, etc.) and synthetic polymers in bioprinting by tuning their printability and cross-linking features, mechanical and thermal properties, biocompatibility, and biodegradability, etc. This review describes the potential of these polymers to support adhesion and proliferation of viable cells to bioprint cell laden constructs, bone, cartilage, skin, and neural tissues, and blood vessels, etc. for various applications in tissue engineering and regenerative medicines. Further, it describes various challenges associated with current bioprinting technology and suggests possible solutions. Although at early stage of development, the potential benefits of bioprinting technology are quite clear and expected to open new gateways in biomedical, pharmaceutics and several other fields in near future., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autologous gastrointestinal tissue has remained the gold-standard reconstructive biomaterial in urology for >100 years. Mucus-secreting epithelium is associated with lifelong metabolic and neuromechanical complications when implanted into the urinary tract. Therefore, the availability of biocompatible tissue-engineered biomaterials such as extracellular matrix (ECM) scaffolds may provide an attractive alternative for urologists. ECMs are decellularised, biodegradable membranes that have shown promise for repairing defective urinary tract segments in vitro and in vivo by inducing a host-derived tissue remodelling response after implantation. In urology, porcine small intestinal submucosa (SIS) and porcine urinary bladder matrix (UBM) are commonly selected as ECMs for tissue regeneration. Both ECMs support ingrowth of native tissue and differentiation of multi-layered urothelial and smooth muscle cells layers while providing mechanical support in vivo. In their native acellular state, ECM scaffolds can repair small urinary tract defects. Larger urinary tract segments can be repaired when ECMs are manipulated by seeding them with various cell types prior to in vivo implantation. In the present review, we evaluate and summarise the clinical potential of tissue engineered ECMs in reconstructive urology with emphasis on their long-term outcomes in urological clinical trials., (Copyright © 2017 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: There is limited data on the impact of calcium (Ca) on acute procedural and clinical outcomes in patients with lesions treated with bioresorbable vascular scaffolds (BRS). We sought to evaluate the effect of calcium on procedural and clinical outcomes in a 'real world' population., Methods: Clinical outcomes were compared between patients with at least 1 moderately or heavily calcified lesion (Ca) and patients with no/mild calcified lesions (non-Ca) enrolled in our institutional BRS registry., Results: 455 patients (N) with 548 lesions (L) treated with 735 BRS were studied. Patients in the Ca group (N=160, L=200) had more complex (AHA B2/C lesion: 69.0% in Ca vs 14.9% in non-Ca, p<0.001) and significantly longer lesions (27.80±15.27 vs 19.48±9.92mm, p<0.001). Overall device success rate was 99.1% with no significant differences between the groups. Despite more aggressive lesion preparation and postdilation compared to non Ca, acute lumen gain was significantly less in Ca lesions (1.50±0.66 vs 1.62±0.69mm, p=0.040) with lower final MLD (2.28±0.41 vs 2.36±0.43, p=0.046). There were no significant differences in all-cause mortality, total definite scaffold thrombosis (ST), target lesion revascularization and myocardial infarction between the 2 groups. Late ST was more frequent in the Ca group compared to non Ca group (late ST: 2.1 vs 0%, p=0.02)., Conclusions: Clinical outcomes after BRS implantation in calcified and non-calcified lesions were similar. A remarkable difference in timing of thrombosis was observed, with an increased rate of late thrombosis in calcified lesions., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Very late scaffold thrombosis (VLScT) occurs more frequently after bioresorbable scaffold (Absorb BVS 1.1, Abbott Vascular, Santa Clara, California) implantation than with metallic everolimus-eluting stents., Objectives: The purpose of this study was to elucidate mechanisms underlying VLScT as assessed by optical coherence tomography (OCT)., Methods: The INVEST (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) registry is an international consortium of investigators who used OCT to examine patients with VLScT., Results: Between June 2013 and May 2017, 36 patients with 38 lesions who had VLScT underwent OCT at 19 centers. VLScT occurred at a median of 20 months (interquartile range: 16 to 27 months) after implantation. At the time of VLScT, 83% of patients received aspirin monotherapy and 17% received dual-antiplatelet therapy. The mechanisms underlying VLScT were (in descending order) scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge-related disease progression (2.6%). Discontinuity (odds ratio [OR]: 110; 95% confidence interval [CI]: 73.5 to 173; p < 0.001), malapposed struts (OR: 17.0; 95% CI: 14.8 to 19.7; p < 0.001), and uncovered struts (OR: 7.3; 95% CI: 6.2 to 8.8; p < 0.001) were more frequent in the thrombosed than the nonthrombosed scaffold regions. In 2 of 16 patients with scaffold discontinuity, intercurrent OCT before VLScT provided evidence of circularly apposed scaffold struts with minimal tissue coverage., Conclusions: The leading mechanism underlying VLScT was scaffold discontinuity, which suggests an unfavorable resorption-related process, followed by malapposition and neoatherosclerosis. It remains to be determined whether modifications in scaffold design and optimized implantation can mitigate the risk of VLScT. (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis [INVEST]; NCT03180931)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Weaving is a resourceful technology which offers a large selection of solutions that are readily adaptable for tissue engineering (TE) of artificial heart valves (HV). The different ways that the yarns are interlaced in this technique could be used to produce complex architectures, such as the three-layer architecture of the leaflets. Once the assembly is complete, growth of cells in the scaffold would occur in the orientation of the yarn, enabling the deposition of extra cellular matrixes proteins in an oriented manner. Weaving technology is a rapidly evolving field that, first, needs to be understood, and then explored by tissue engineers, so that it could be used to create efficient scaffolds. Similarly, the textile engineers need to gain a basic understanding of key structural and mechanical aspects of the heart valve. The aim of this review is to provide the platform for joining these two fields and to enable cooperative research efforts. Moreover, examples of woven medical products and patents as well as related publication are discussed in this review, nevertheless due to the large, and continuously growing volume of data, only the aspects strictly associated with HVTE lay in the scope of this paper., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The development of in vitro artificial small intestines that realistically mimic in vivo systems will enable vast improvement of our understanding of the human gut and its impact on human health. Synthetic in vitro models can control specific parameters, including (but not limited to) cell types, fluid flow, nutrient profiles and gaseous exchange. They are also "open" systems, enabling access to chemical and physiological information. In this work, we demonstrate the importance of gut surface topography and fluid flow dynamics which are shown to impact epithelial cell growth, proliferation and intestinal cell function. We have constructed a small intestinal bioreactor using 3-D printing and polymeric scaffolds that mimic the 3-D topography of the intestine and its fluid flow. Our results indicate that TEER measurements, which are typically high in static 2-D Transwell apparatuses, is lower in the presence of liquid sheer and 3-D topography compared to a flat scaffold and static conditions. There was also increased cell proliferation and discovered localized regions of elevated apoptosis, specifically at the tips of the villi, where there is highest sheer. Similarly, glucose was actively transported (as opposed to passive) and at higher rates under flow.

Background: Data from randomized controlled trials have shown that the ABSORB BVS is non-inferior to Cobalt Chromium everolimus-eluting stents at 2years., Methods & Results: The EVERBIO II trial (Comparison of Everolimus- and Biolimus-Eluting Coronary Stents with Everolimus-Eluting Bioresorbable Vascular Scaffold) is a single-center, assessor-blind, randomized controlled trial enrolling 240 patients with an allocation ration of 1:1:1 conducted at University and Hospital Fribourg, Switzerland. The studied devices were an everolimus-eluting persistent polymer stent (EES), a biolimus-eluting stent with bioabsorbable polymer (BES) and a fully bioresorbable vascular scaffold (BVS). Clinical end points collected at 9months, 12months, and 2years, were academic research consortium defined composites, device thrombosis and target-vessel revascularization. Clinical follow-up at 2years was available in 96% (N=77) of patients in the EES group, in 100% (N=80) in the BES and 99% (N=77) in the BVS group. The device-oriented composite end point of cardiac death, target-vessel myocardial infarction and target-lesion revascularization occurred in 13 (16%) patients treated with EES, in 7 (9%) patients treated with BES and in 16 (21%) patients treated with BVS. There was no significant difference when the metallic stents were compared to the BVS (p=0.12). There was one late scaffold thrombosis throughout the trial in the BVS group, and no definite stent thrombosis in either EES or BES treated patients., Conclusions: The current analysis shows no significant differences with regard to clinical outcomes at 2years between BVS and the best-in-class metallic DES. Event rates were numerically higher in BVS-treated patients. However, when BVS were compared to BES alone, the occurrence of device related adverse events was significantly increased., (Copyright © 2017. Published by Elsevier B.V.)

Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue. In this article we provide an overview about our conceptual design and process of the clinical translation of scaffold-based bone tissue engineering applications.

The ability to treat large tissue defects with customized, patient-specific scaffolds is one of the most exciting applications in the tissue engineering field. While an increasing number of modestly sized tissue engineering solutions are making the transition to clinical use, successfully scaling up to large scaffolds with customized geometry is proving to be a considerable challenge. Managing often conflicting requirements of cell placement, structural integrity, and a hydrodynamic environment supportive of cell culture throughout the entire thickness of the scaffold has driven the continued development of many techniques used in the production, culturing, and characterization of these scaffolds. This review explores a range of technologies and methods relevant to the design and manufacture of large, anatomically accurate tissue-engineered scaffolds with a focus on the interaction of manufactured scaffolds with the dynamic tissue culture fluid environment. Biotechnol. Bioeng. 2017;114: 1129-1139. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Bioresorbable coronary stents have been introduced into clinical practice to improve the outcomes of patients treated with percutaneous coronary intervention. The everolimus-eluting bioresorbable vascular scaffold (BVS) is the most studied of these stent platforms; however, recent trials comparing BVS with everolimus-eluting metallic stents (EES) raised concerns about BVS safety. We aimed to assess the efficacy and safety of BVS versus EES in patients undergoing percutaneous coronary intervention., Methods: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, scientific sessions abstracts, and relevant Web sites for randomized trials with a follow-up of ≥2 years investigating percutaneous coronary interventions with BVS versus EES. The primary outcomes of our analysis were definite/probable stent thrombosis (ST) and target lesion failure (TLF; device-oriented composite end point of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization [TLR]). Secondary outcomes were target vessel myocardial infarction, TLR, and cardiac death. We calculated the risk estimates for main outcomes according to a fixed-effect model., Results: We included 7 trials comprising data for 5583 patients randomized to receive either a BVS (n=3261) or an EES (n=2322). Median follow-up was 24 months (range, 24-36 months). Patients treated with BVS had a higher risk of definite/probable ST compared with patients treated with EES (odds ratio, 3.33; 95% confidence interval, 1.97-5.62; P <0.00001). In particular, patients with BVS had a higher risk of subacute, late, and very late ST, whereas the risk of acute ST was similar. Patients treated with BVS compared with EES had a higher risk at 2 years of TLF (odds ratio, 1.47; 95% confidence interval, 1.14-1.90; P =0.003), driven mainly by an increased risk of target vessel myocardial infarction (odds ratio, 1.73; 95% confidence interval, 1.31-2.28; P =0.0001; I 2 =0%) and of TLR (odds ratio, 1.27; 95% confidence interval, 1.00-1.62; P =0.05). Of importance, the risk of TLF and TLR for patients with BVS was higher between 1 and 2 years, whereas there was no difference in the first year. Risk of cardiac death was similar between the 2 groups., Conclusions: Our meta-analysis of randomized trials with a follow-up of ≥2 years demonstrated a higher risk of ST and of TLF in patients treated with BVS compared with EES. Of note, BVS had a higher risk of subacute, late, and very late ST, whereas the risk of TLF and TLR was higher between 1 and 2 years., (© 2017 American Heart Association, Inc.)

Regenerative medicine is a burgeoning interdisciplinary research field that can impact healthcare by offering new therapeutic strategies to replace or regenerate human cells, tissues, or organs with the ultimate goal of restoring or establishing normal human functions. The past decade has seen significant progress of regenerative medicine in China, the world's most populous developing country. With government backing, the progress in regenerative medicine is driven by increasing medical demands of people, accompanied by the economic growth, population aging, and lifestyle change in China. Although regenerative medicine encompasses many components, tissue engineering and stem cell technology are generally considered the two key players. In this review article, we outline the representative achievements in the research and application of tissue engineering, stem cell technology, and other regenerative medical strategies attained by various research groups in China, and highlight the major contributions and features of several outstanding studies made by leading Chinese researchers. Where possible, we discuss the unique opportunities and challenges for advancement of regenerative medicine in China. It is our hope that this review will stimulate new research directions for regenerative medicine in general, and encourage strategic collaborations between the east and the west in particular, so that the clinical translation of regenerative medicine can be accelerated to benefit mankind., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cardiovascular diseases are the leading cause of global deaths. The current paradigm in medicine seeks novel approaches for the treatment of progressive or end-stage diseases. The organ transplantation option is limited in availability, and unfortunately, a significant number of patients are lost while waiting for donor organs. Animal studies have shown that upon myocardial infarction, it is possible to stop adverse remodeling in its tracks and reverse with tissue engineering methods. Regaining the myocardium function and avoiding further deterioration towards heart failure can benefit millions of people with a significantly lesser burden on healthcare systems worldwide. The advent of induced pluripotent stem cells brings the unique advantage of testing candidate drug molecules on organ-on-chip systems, which mimics human heart in vitro. Biomimetic three-dimensional constructs that contain disease-specific or normal cardiomyocytes derived from human induced pluripotent stem cells are a useful tool for screening drug molecules and studying dosage, mode of action and cardio-toxicity. Tissue engineering approach aims to develop the treatments for heart valve deficiency, ischemic heart disease and a wide range of vascular diseases. Translational research seeks to improve the patient's quality of life, progressing towards developing cures, rather than treatments. To this end, researchers are working on tissue engineered heart valves, blood vessels, cardiac patches, and injectable biomaterials, hence developing new ways for engineering bio-artificial organs or tissue parts that the body will adopt as its own. In this review, we summarize translational methods for cardiovascular tissue engineering and present useful tables on pre-clinical and clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Purpose of Review: Drug-eluting stents are the mainstay in the treatment of coronary artery disease using percutaneous coronary intervention. Innovations developed to overcome the limitations of prior generations of stents include biodegradable polymer stents, drug-eluting stents without a polymer, and bioabsorbable scaffolds. Our review briefly discusses the clinical profiles of first- and second-generation coronary stents, and provides an up-to-date overview of design, technology, and clinical safety and efficacy profiles of newer generation coronary stents discussing the relevant clinical trials in this rapidly evolving area of interventional cardiology., Recent Findings: Drug-eluting stents have previously been shown to be superior to bare metal stents. Second-generation everolimus-eluting stents have proven to have superior outcomes compared with first-generation paclitaxel- and sirolimus-eluting stents, and the second-generation zotarolimus-eluting stents appear to be similar to the everolimus-eluting stents, though with a lesser degree of evidence. Stents with biodegradable polymers have not been shown to be superior to everolimus-eluting stents. Bioabsorbable scaffolds have not demonstrated better outcomes than current standard treatment with second-generation drug-eluting stents but have showed a concerning signal of late and very late stent thrombosis. Everolimus-eluting stents have the most favorable outcomes in terms of safety as well as efficacy in patients undergoing percutaneous coronary intervention. Newer innovations such as biodegradable polymers and bioabsorbable scaffolds lack clinical data to replace second-generation drug-eluting stents as standard of care.

Purpose of Review: Whole lung tissue engineering is a relatively new area of investigation. In a short time, however, the field has advanced quickly beyond proof of concept studies in rodents and now stands on the cusp of wide-spread scale up to large animal studies. Therefore, this technology is ever closer to being directly clinically relevant., Recent Findings: The main themes in the literature include refinement of the fundamental components of whole lung engineering and increasing effort to direct induced pluripotent stem cells and lung progenitor cells toward use in lung regeneration. There is also increasing need for and emphasis on functional evaluation in the lab and in vivo, and the use of all of these tools to construct and evaluate forthcoming clinically scaled engineered lung., Summary: Ultimately, the goal of the research described herein is to create a useful clinical product. In the intermediate time, however, the tools described here may be employed to advance our knowledge of lung biology and the organ-specific regenerative capacity of lung stem and progenitor cells.

During the past several decades, major advances and improvements now promote better treatment options for cardiovascular diseases. However, these diseases still remain the single leading cause of death worldwide. The rapid development of cardiac tissue engineering has provided the opportunity to potentially restore the contractile function and retain the pumping feature of injured hearts. This conception of cardiac tissue engineering can enable researchers to produce autologous and functional biomaterials which represents a promising technique to benefit patients with cardiovascular diseases. Such an approach will ultimately reshape existing heart transplantation protocols. Notable efforts are accelerating the development of cardiac tissue engineering, particularly to create larger tissue with enhanced functionality. Decellularized scaffolds, polymer synthetics fibrous matrix, and natural materials are used to build robust cardiac tissue scaffolds to imitate the morphological and physiological patterns of natural tissue. This ultimately helps cells to implant properly to obtain endogenous biological capacity. However, newer designs such as the hydrogel scaffold-free matrix can increase the applicability of artificial tissue to engineering strategies. In this review, we summarize all the methods to produce artificial cardiac tissue using scaffold and scaffold-free technology, their advantages and disadvantages, and their relevance to clinical practice.

Tissue engineering is considered one of the most important therapeutic strategies of regenerative medicine. The main objective of these new technologies is the development of substitutes made with biomaterials that are able to heal, repair or regenerate injured or diseased tissues and organs. These constructs seek to unlock the limited ability of human tissues and organs to regenerate. In this review, we highlight the convenient intrinsic properties of gelatin for the design and development of advanced systems for tissue engineering. Gelatin is a natural origin protein derived from collagen hydrolysis. We outline herein a state of the art of gelatin-based composites in order to overcome limitations of this polymeric material and modulate the properties of the formulations. Control release of bioactive molecules, formulations with conductive properties or systems with improved mechanical properties can be obtained using gelatin composites. Many studies have found that the use of calcium phosphate ceramics and diverse synthetic polymers in combination with gelatin improve the mechanical properties of the structures. On the other hand, polyaniline and carbon-based nanosubstrates are interesting molecules to provide gelatin-based systems with conductive properties, especially for cardiac and nerve tissue engineering. Finally, this review provides an overview of the different types of gelatin-based structures including nanoparticles, microparticles, 3D scaffolds, electrospun nanofibers and in situ gelling formulations. Thanks to the significant progress that has already been made, along with others that will be achieved in a near future, the safe and effective clinical implementation of gelatin-based products is expected to accelerate and expand shortly., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The foundation of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells. Tissue engineering utilizes living cells as engineering materials implanted, seeded or bioplotted into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called scaffolds, are critical, both ex vivo and in vivo, to influence their own microenvironments. Scaffolds can serve the following purposes: allow cell attachment and migration, deliver and retain cells and biochemical factors, enable diffusion of vital cell nutrients or expressed products, exert certain mechanical and biological influences to modify the behaviour of the cell phase. Traditional tissue engineering strategies typically employ a "top-down" approach, in which cells are seeded on a biodegradable three dimensional monolithic polymeric scaffold. More recently they have been updated by a "bottom- up" approach, also known as modular tissue engineering; it is aimed to address the challenge of recreating bio-mimetic structures by designing structural micro-features to build modular tissues, used as building blocks to re-create larger ones. These two different approaches will require scaffolds with given characteristics obtainable by choosing different fabrication technologies. Conventional and innovative supercritical technologies for monolithic scaffold production or biopolymer micro/nano devices will be discussed in this chapter. Some examples of bone and cartilage tissue engineering produced by using modular scaffold will be also discussed, as well as the fabrication of artificial extracellular matrix for spatio-temporally delivery of biological and mechanical signal to address cell fate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Tendon injury is a clinical, societal and economical issue. Moreover, tendon repair represents an important clinical challenge, partly due to the mechanical constraints that occur at the junctions with muscle and bone. Several strategies have been developed for tendon repair. In this review, we first assess the importance of tendon injuries from different sites and their causes. After a short overview of tendon three-dimensional organization, the complexity of the perfect repair quest is presented ranging from current clinical procedures to new engineering scaffolds. We then sum up tendon engineering requirements and focus on new collagen-based scaffolds, which raise promising prospects to mimic and repair tendon. In particular, we survey quantitatively a large panel of techniques to produce these scaffolds, detailing their principle and recent improvements., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Following fertilization, the blastocyst has to complete two distinct steps to assure further development of pregnancy. After apposition it establishes a firm connection with the luminal epithelium of the endometrium (attachment) and subsequently enters the decidualizing stroma (invasion). If this step is not achieved successfully, fertility problems arise. Development of the placenta ensures an adequate supply of nutrients and gas between the mother and the fetus. Preeclampsia is a prevalent disorder arising from defects in the process of placentation. It is associated with an increase of maternal morbidity and mortality. Numerous attempts have been made in order to elucidate the etiology of the syndrome and identify women at risk. The lack of reliable animal models has turned the attention to the development of in vitro assays, which could provide a better insight into the individual processes that will later trigger preeclampsia symptoms. In particular, 3D in vitro models more closely resemble the complexity of the extracellular environment. The choice of the scaffolding material should be done carefully as cell-matrix interactions are very often as important as cell-cell interactions for the correct attachment, proliferation and differentiation of cells. The following review is aimed to provide a general overview of the scaffolds available for the in vitro modeling of these complicated systems as well as to discuss the importance surrounding the choice of the scaffolding material and its influence on the results obtained., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Nanotechnology is an exciting emerging field with multiple applications in skin regeneration. Nanofibers have gained special attention in skin regeneration based on their structural similarity to the extracellular matrix. A wide variety of polymeric nanofibers with distinct properties have been developed and tested as scaffolds for skin regeneration. Besides providing support for tissue repair, nanofibrous materials can act as delivery systems for drugs, proteins, growth factors, and other molecules. Moreover, the morphology, biodegradability, and other functionalities of nanofibrous materials can be controlled towards specific conditions of wound healing. Other nanostructured drug delivery systems, such as nanoparticles, micelles, nanoemulsions, and liposomes, have been used to improve wound healing at different stages. These nanoscale delivery systems have demonstrated several benefits for the wound healing process, including reduced cytotoxicity of drugs, administration of poorly water-soluble drugs, improved skin penetration, controlled release properties, antimicrobial activity, and protection of drugs against light, temperature, enzymes or pH degradation, as well as stimulation of fibroblast proliferation and reduced inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Hydroxyapatite (HAp) is a complicated ceramic material that varies between the way it appears in biological systems and how it is synthesized as various calcium phosphates. HAp varies in chemical composition of substituting atoms, crystallinity, grain size and electrical polarization. HAp can form solid to macro-, micro- and nanoporous structures. Also, particulate HAp can have highly porous structure. HAp can be used as coatings for metal implants in thicknesses from hundreds of microns down to hundreds of nanometers. Cotton wool-like HAp fibers can be electrospun compounded with polymers (or without) for tissue engineering (TE) scaffolds. This review describes the features of HAp that may be utilized further in developing novel applications. As a nanomaterial HAp has been applied for drug delivery. The adsorption of proteins and other compounds can be adjusted by modifying HAp composition, electrical polarization and wettability. Of special interest are the bisphosphonates that bind to HAp and thereby can be used to treat bone loss and also couple other drugs to the mineral. A new area for HAp constructs may appear in treating metallosis. HAp coating may function as a scavenger for the ions release from metal implants and thereby inhibit the adverse effects of the ion burden for the body. So far HAp is considered as safe biomaterial but nano HAp may insidiously possess adverse effects especially when ingested by cells and eliciting excess intracellular calcium. Thereby critical approach also for HAp biomaterials is of utmost importance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)