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To measure the force applied along the anterior and posterior vaginal walls in a cohort of 46 patients measured by a fiber-optic pressure sensor and determine if this correlates with vaginal parity and pelvic organ prolapse (POP).An intravaginal fiber-optic sensor measured pressure at nine locations along the anterior and posterior vaginal walls during a maximal voluntary pelvic floor muscle contraction (MVC). An automated probe dilation cycle measured the tissue resistance incorporating the vagina and surrounding anatomy. MVC and resting tissue resistance (RTR) were assessed between subjects grouped by the number of vaginal births and prolapse stage.A previous vaginal birth was associated with a significant threefold decrease in the overall anterior pressure measurement during MVC. Decreased anterior pressure measurements were observed at Sensors 1 and 3 (distal vagina) and, posteriorly at Sensors 4-6 (midvagina). Women with Stage 2 posterior prolapse exhibited a decreased MVC pressure in the midvagina than those with Stage 0/1. In this pilot study, there was no difference in the vaginal wall RTR according to previous vaginal birth or stage of prolapse.This pilot study found that a decrease in vaginal pressure measured during MVC is associated with vaginal birth and with posterior POP. Greater sample size is required to assess the role of resting tissue pressure measurement.

Mesenchymal stem cells (MSCs) that meet the International Society for Cellular Therapy (ISCT) criteria are obtained from placental tissue by plastic adherence. Historically, no known single marker was available for isolating placental MSCs (pMSCs) from the decidua basalis. As the decidua basalis is derived from the regenerative endometrium, we hypothesised that SUSD2, an endometrial perivascular MSC marker, would purify maternal perivascular pMSC. Perivascular pMSCs were isolated from the maternal placenta using SUSD2 magnetic bead sorting and assessed for the colony-forming unit-fibroblasts (CFU-F), surface markers, and in vitro differentiation into mesodermal lineages. Multi-colour immunofluorescence was used to colocalise SUSD2 and α-SMA, a perivascular marker in the decidua basalis. Placental stromal cell suspensions comprised 5.1%SUSD2+ cells. SUSD2 magnetic bead sorting of the placental stromal cells increased their purity approximately two-fold. SUSD2+ pMSCs displayed greater CFU-F activity than SUSD2- stromal fibroblasts (pSFs). However, both SUSD2+ pMSC and SUSD2- pSF underwent mesodermal differentiation in vitro, and both expressed the ISCT surface markers. Higher percentages of cultured SUSD2+ pMSCs expressed the perivascular markers CD146, CD140b, and SUSD2 than SUSD2- pSFs. These findings suggest that SUSD2 is a single marker that enriches maternal pMSCs, suggesting they may originate from eMSC. Placental decidua basalis can be used as an alternative source of MSC for clinical translation in situations where there is no access to endometrial tissue.

Cellular therapy is an emerging field in clinical and personalised medicine. Many adult mesenchymal stem/progenitor cells (MSC) or pluripotent derivatives are being assessed simultaneously in preclinical trials for their potential treatment applications in chronic and degenerative human diseases. Endometrial mesenchymal stem/progenitor cells (eMSC) have been identified as clonogenic cells that exist in unique perivascular niches within the uterine endometrium. Compared with MSC isolated from other tissue sources, such as bone marrow and adipose tissue, eMSC can be extracted through less invasive methods of tissue sampling, and they exhibit improvements in potency, proliferative capacity, and control of culture-induced differentiation. In this review, we summarize the potential cell therapy and tissue engineering applications of eMSC in pelvic organ prolapse (POP), emphasising their ability to exert angiogenic and strong immunomodulatory responses that improve tissue integration of novel surgical constructs for POP and promote vaginal tissue healing.

AIMS Pelvic floor disorders (PFDs) in women are a major public health concern. Current clinical methods for assessing PFDs are either subjective or confounded by interference from intra-abdominal pressure (IAP). This study introduces an intravaginal probe that can determine distributed vaginal pressure during voluntary exercises and measures the degree of vaginal tissue support independent of IAP fluctuations. METHODS An intravaginal probe was fabricated with 18 independent fiber-optic pressure transducers positioned along its upper and lower blades. Continuous pressure measurement along the anterior and posterior vaginal walls during the automated expansion of the probe enabled the resistance of the tissue to be evaluated as a function of displacement, in a manner reflecting the elastic modulus of the tissue. After validation in a simulated vaginal phantom, in vivo measurements were conducted in the relaxed state and during a series of voluntary exercises to gauge the utility of the device in women. RESULTS The probe reliably detected variations in the composition of sub-surface material in the vaginal phantom. During in-vivo measurements the probe detected distributed tissue elasticity in the absence of IAP change. In addition, the distribution of pressure along both anterior and posterior vaginal walls during cough, Valsalva and pelvic floor contraction was clearly resolved with a large variation observed between subjects. CONCLUSIONS Our data highlight the potential for the probe to assess the integrity of the vagina wall and support structures as an integrated functional unit. Further in vivo trials are needed to correlate data with clinical findings to assist in the assessment of PFDs.

Aloe vera (AV), a succulent plant belonging to the Liliaceae family, has been widely used for biomedical and pharmaceutical application. Its popularity stems from several of its bioactive components that have anti-oxidant, anti-microbial, anti-inflammatory and even immunomodulatory effects. Given such unique multi-modal biological impact, AV has been considered as a biomaterial for regenerative medicine and tissue engineering applications, where tissue repair and neo-angiogenesis are vital. This review outlines the growing scientific evidence that demonstrates the advantage of AV as tissue engineering scaffolds. We particularly highlight the recent advances in the application of AV-based scaffolds. From a tissue engineering perspective, it is pivotal that the implanted scaffolds strike an appropriate foreign body response to be well-accepted in the body without complications. Herein, we highlight the key cellular processes that regulate the foreign body response to implanted scaffolds and underline the immunomodulatory effects incurred by AV on the innate and adaptive system. Given that AV has several beneficial components, we discuss the importance of delving deeper into uncovering its action mechanism and thereby improving material design strategies for better tissue engineering constructs for biomedical applications.

There is an increasing need for bone substitutes for reconstructive orthopedic surgery following removal of bone tumors. Despite the advances in bone regeneration, the use of autologous mesenchymal stem cells (MSC) presents a significant challenge, particularly for the treatment of large bone defects in cancer patients. This study aims at developing new chemokine-based technology to generate biodegradable scaffolds that bind pharmacologically active proteins for regeneration/repair of target injured tissues in patients. Primary MSC were cultured from the uninvolved bone marrow (BM) of cancer patients and further characterized for "stemness". Their ability to differentiate into an osteogenic lineage was studied in 2D cultures as well as on 3D macroporous PLGA scaffolds incorporated with biomacromolecules bFGF and homing factor chemokine stromal-cell derived factor-1 (SDF1). MSC from the uninvolved BM of cancer patients exhibited properties similar to that reported for MSC from BM of healthy individuals. Macroporous PLGA discs were prepared and characterized for pore size, architecture, functional groups, thermostability, and cytocompatibility by ESEM, FTIR, DSC, and CCK-8 dye proliferation assay, respectively. It was observed that the MSC+PLGA+bFGF+SDF1 construct cultured for 14 days supported significant cell growth, osteo-lineage differentiation with increased osteocalcin expression, alkaline phosphatase secretion, calcium mineralization, bone volume, and soluble IL6 compared to unseeded PLGA and PLGA+MSC, as analyzed by confocal microscopy, biochemistry, ESEM, microCT imaging, flow cytometry, and EDS. Thus, chemotactic biomacromolecule SDF1-guided tissue repair/regeneration ability of MSC from cancer patients opens up the avenues for development of "off-the-shelf" pharmacologically active construct for optimal repair of the target injured tissue in postsurgery cancer patients, bone defects, damaged bladder tissue, and radiation-induced skin/mucosal lesions.

Mesenchymal stem cells (MSCs) that meet the International Society for Cellular Therapy (ISCT) criteria are obtained from placental tissue by plastic adherence. Historically, no known single marker was available for isolating placental MSCs (pMSCs) from the decidua basalis. As the decidua basalis is derived from the regenerative endometrium, we hypothesised that SUSD2, an endometrial perivascular MSC marker, would purify maternal perivascular pMSC. Perivascular pMSCs were isolated from the maternal placenta using SUSD2 magnetic bead sorting and assessed for the colony-forming unit-fibroblasts (CFU-F), surface markers, and in vitro differentiation into mesodermal lineages. Multi-colour immunofluorescence was used to colocalise SUSD2 and α-SMA, a perivascular marker in the decidua basalis. Placental stromal cell suspensions comprised 5.1%SUSD2

Pelvic organ prolapse is a common condition that affects 1 in 4 women across all age groups. It is mainly caused by vaginal birth injury and can be exacerbated by obesity and increased age. Until recently, treatment strategies often used non-degradable synthetic meshes for reconstructive surgery. However, owing to their frequent, unacceptable rate of adverse events such as mesh erosion, transvaginal meshes have been banned in many countries. Recent reports have highlighted the urgent need for biocompatible design of meshes for a safe and effective treatment in the long term. This study reports the design and evaluation of a novel, elastin based degradable mesh using an ovine model of POP as a potential surgical treatment. Elastin is a protein component of the ECM and provides elasticity to tissues throughout the body. Tropoelastin, the monomer subunit of elastin, has been used with success in electrospun constructs as it is a naturally cell interactive polymer. Biomaterials that incorporate tropoelastin support cell attachment and proliferation, and have been proven to encourage elastogenesis and angiogenesis in vitro and in vivo. The biological properties of tropoelastin were combined with the physical properties of PCL, a degradable synthetic polymer, with the aim of producing, characterizing and assessing the performance of continuous tropoelastin:PCL electrospun yarns. Using a modified spinneret electrospinning system and adjusting settings based on relative humidity, four blends of tropoelastin:PCL yarns were fabricated with concentration ratios of 75:25, 50:50, 25:75 and 0:100. Yarns were assessed for ease of manufacture, fibrous architecture, protein/polymer content, yarn stability - including initial tropoelastin release, mechanical strength, and ability to support cell growth. Based on overall favorable properties, a mesh woven from the 50:50 tropoelastin:PCL yarn was implanted into the vagina of a parous ewe with vaginal wall weakness as a model of pelvic organ prolapse. This mesh showed excellent integration with new collagen deposition by SEM and a predominant M2 macrophage response with few pro-inflammatory M1 macrophages after 30 days. The woven tropoelastin:PCL electrospun mesh shows potential as an alternative to non-degradable, synthetic pelvic organ prolapse mesh products., Graphical abstract Image 1

Objective: Endometriosis is a common and painful condition characterized by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of by endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy.Results: Treatment with 5E1, reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

Objective Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. Results Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

There is a growing need for anti-microbial materials in several biomedical application areas, such are hernia, skin grafts as well as gynecological products, owing to the complications caused by infection due to surgical biomaterials. The anti-microbial effects of silver in the form of nanoparticles, although effective, can be toxic to surrounding cells. In this study, we report, for the first time, a novel biomedical application of Ag0.3Na1.7La2Ti3O10-layered perovskite particles, blended with poly(L-lactide-co-glycolide) (PLGA), aimed at designing anti-microbial and tissue engineering scaffolds. The perovskite was incorporated in three concentrations of 1, 5, 10 and 15 w/w% and electrospun using dimethylformamide (DMF) and chloroform. The morphology of the resultant nanofibers revealed fiber diameters in the range of 408 to 610 nm by scanning electron microscopy. Mechanical properties of perovskite-based nanofibers also matched similar mechanical properties to human skin. We observed impressive anti-microbial activity, against Gram-negative, Gram-positive bacteria and even fungi, to Ag0.3Na1.7La2Ti3O10 in powder as well as nanofiber-incorporated forms. Furthermore, cytotoxicity assay and immunocytochemistry revealed that perovskite-based nanofibers promoted the proliferation of human dermal fibroblasts whist maintaining normal cellular protein expression. Our study shows that perovskite-nanofibers have potential as scaffolds for biomedical applications with anti-microbial needs.

The in vitro degradation of magnesium (Mg) alloys containing low levels of strontium (Sr, 0.05, 0.1 and 0.2 wt%), with and without addition of zinc (Zn, 0.5 and 1.0 wt%), was studied for potential use in orthopaedics for fracture treatment. Alloying Mg with Sr was selected as a promising strategy to utilise the biological effect of Sr in inducing accelerated bone tissue growth. The influence of controlled alloying upon degradation rate was studied via electrochemical measurements and immersion tests in minimum essential medium (MEM). Immersion testing revealed a comparable degradation rate of the alloys tested herein, indicating no detrimental effect of Sr on degradation. Cytotoxicity experiments on primary mouse osteoblasts indicated good biocompatibility and enhanced proliferation of osteoblasts for all the tested Mg alloys. Potentiodynamic polarisation testing further confirmed that addition of low-levels of Sr had a minor influence on cathodic kinetics, with a slight inhibition of anodic kinetics. In contrast, the addition of Zn as a ternary element moderated both anodic and cathodic kinetics of Mg-Sr alloys.

Simultaneous capture of different air pollutants including aerosols and volatile organic compound (VOC) is demonstrated using composite polyacrylonitrile (PAN)/β-cyclodextrin (β-CD) nanofiber membrane. Aerosol filtration along with VOCs adsorption in one step remains a challenge due to differences in the physical and chemical properties of these air pollutants. PAN/β-CD composite electrospun nanofiber membranes (ENMs) were produced with different concentrations of β-CD. The surface modification of the composite ENM was confirmed by X-ray photoelectron spectroscopy (XPS), field emission-scanning electron microscopy (FE-SEM) and water contact angles. PAN/β-CD composite ENMs showed excellent air filtration performance (>95% filtration efficiency with a relatively low pressure drop of 112 Pa). Formaldehyde (HCHO) adsorption was determined using a simple jar method and xylene adsorption by UV spectroscopy. HCHO and xylene adsorption found better by 66% and 73%, respectively, compared to pristine PAN ENM despite a reduction in fiber surface area. The composite ENMs were found to be nontoxic to human lung cell line, suggesting that it is a good candidate for respiratory filter media for simultaneous air filtration and VOC adsorption.

© 2018 American Chemical Society. Bone osteogenesis is a complex phenomenon dependent on numerous microenvironmental cues, with their synchrony regulating cellular functions, such as mechanical signaling, survival, proliferation, and differentiation, as well as controlled regional specification of skeletal progenitor cell fate. Therefore, obtaining a mechanistic understanding of cellular response to a microenvironment is now coming into intense focus, which will facilitate the design of programmable biomaterials for regenerative medicine. State-of-the-art nanomaterial synthesis and self-assembly processes yield complex structures that mimic surface properties, composition, and partially the morphology of the extracellular matrix. However, determining key structural properties that control cell attachment has been challenging and contradictory results are reported regarding the mechanisms and roll of nanostructured materials. Here, we significantly improve osteogenesis on bioinert substrates, demonstrating an exemplary organic-inorganic interface for superior prosthesis biointegration. We identify critical microscale hierarchical features that drastically enhance the cellular response to the same nanoscale architecture. It was observed that hierarchical morphologies, with a porosity above 80%, promote early-stage osteoinduction, as indicated by extensive coating ingrowth and nanofilopodia formation. We determined that cellular integration was mediated by two-way recognition of specific nano- and microtopographical cues between the host tissue and cellular microenvironment. This has allowed us to detail a set of determinant features for the nanofabrication of advanced prosthesis coatings that may ultimately improve implant longevity.

Cellular therapy is an emerging field in clinical and personalised medicine. Many adult mesenchymal stem/progenitor cells (MSC) or pluripotent derivatives are being assessed simultaneously in preclinical trials for their potential treatment applications in chronic and degenerative human diseases. Endometrial mesenchymal stem/progenitor cells (eMSC) have been identified as clonogenic cells that exist in unique perivascular niches within the uterine endometrium. Compared with MSC isolated from other tissue sources, such as bone marrow and adipose tissue, eMSC can be extracted through less invasive methods of tissue sampling, and they exhibit improvements in potency, proliferative capacity, and control of culture-induced differentiation. In this review, we summarize the potential cell therapy and tissue engineering applications of eMSC in pelvic organ prolapse (POP), emphasising their ability to exert angiogenic and strong immunomodulatory responses that improve tissue integration of novel surgical constructs for POP and promote vaginal tissue healing.

Nondegradable transvaginal polypropylene meshes for treating pelvic organ prolapse (POP) are now generally unavailable or banned. In this review, we summarize recent developments using tissue engineering approaches combining alternate degradable scaffolds with a novel source of mesenchymal stem/stromal cells from human endometrium (eMSC).Tissue engineering constructs comprising immunomodulatory, reparative eMSC and biomimetic materials with nanoarchitecture are a promising approach for vaginal repair and improving outcomes of POP surgery. Culture expansion of eMSC that maintains them (and other MSC) in the undifferentiated state has been achieved using a small molecule transforming growth factor-β receptor inhibitor, A83-01. The mechanism of action of A83-01 has been determined and its suitability for translation into the clinic explored. Novel blends of electrospun synthetic and natural polymers combined with eMSC shows this approach promotes host cell infiltration and slows biomaterial degradation that has potential to strengthen the vaginal wall during healing. Improving the preclinical ovine transvaginal surgical model by adapting the human clinical POP-Quantification system for selection of multiparous ewes with vaginal wall weakness enables assessment of this autologous eMSC/nanobiomaterial construct.A tissue engineering approach using autologous eMSC with degradable nanobiomaterials offers a new approach for treating women with POP.

Endometrial mesenchymal stem/stromal cells (eMSCs) exhibit excellent regenerative capacity in the endometrial lining of the uterus following menstruation and high proliferative capacity in vitro. Bioprinting eMSCs onto a mesh could be a potential therapy for Pelvic Organ Prolapse (POP). This study reports a novel strategy targeting vaginal repair using bioprinting of eMSCs encapsulated in a hydrogel and3D melt electrospun mesh to generate a tissue engineering construct. Following a CAD, 3D printed poly e-caprolactone (PCL) meshes were fabricated using melt electrospinning (MES) at different temperatures using a GMP clinical grade GESIM Bioscaffolder. Electron and atomic force microscopies revealed that MES meshes fabricated at 100°C and with a speed 20 mm/sec had the largest open pore diameter (47.2 ± 11.4 μm) and the lowest strand thickness (121.4 ± 46 μm) that promoted optimal eMSC attachment. An Aloe Vera-Sodium Alginate (AV-ALG) composite based hydrogel was optimised to a 1:1 mixture (1%AV-1%ALG) and eMSCs, purified from human endometrial biopsies, were then bioprinted in this hydrogel onto the MES printed meshes. Acute in vivo foreign body response assessment in NSG mice revealed that eMSC printed on MES constructs promoted tissue integration, eMSC retention and an anti-inflammatory M2 macrophage phenotype characterised by F4/80+CD206+ colocalization. Our results address an unmet medical need highlighting the potential of alternative 3D bioprinted eMSC-MES meshes as a novel approach to overcome the current challenges with non-degradable knitted meshes in POP treatment.

Vaginal childbirth causes significant maternal tissue injury which can later leads to incurable disorders such as pelvic organ prolapse (POP). This study introduces an immediate vaginal tissue treatment using Aloe Vera (AV)-Alginate (ALG) hydrogel (Hyd) for delivering maternal endometrium derived Mesenchymal stem cells (eMSCs) to promote early healing in a rat simulated birth injury (SBI) model. Vaginal trauma after SBI was evidenced by increased vaginal diameter and inflammatory response. A lack of therapy showed significant reduction of smooth muscle content, increased elastin and increased tissue stiffness, indicative of fibrotic healing. Local injection with hydrogel (Hyd T) or with eMSC in hydrogel (Hyd/eMSC T) had significant impact on birth injury reversal. Hyd/eMSC T significantly improvement smooth muscle and elastin content, comparable to uninjured control vagina. At the nanoscopic level, injury caused disorganisation of structural collagen with increased D period but intervention with Hyd/eMSC T, normalised collagen structure and significantly reduced tissue stiffness. Hyd/eMSC injection showed significant immunomodulation evidenced by lowered M1:M2 ratio while restoring connective tissue composition after 6-weeks. Immediate treatment of severe vaginal birth trauma with therapeutic eMSCs delivered in AV-ALG hydrogel may be a potential new treatment strategy for healing birth injury and preventing future POP in women.

Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation.

Pelvic organ prolapse (POP) is a hidden women’s health disorder that impacts 1 in 4 women across all age groups. Surgical intervention has been the only treatment option, often involving non-degradable meshes, with variable results. However, recent reports have highlighted the adverse effects of meshes in the long term, which involve unacceptable rates of erosion, chronic infection and severe pain related to mesh shrinkage. Therefore, there is an urgent unmet need to fabricate of new class of biocompatible meshes for the treatment of POP. This review focuses on the causes for the downfall of commercial meshes, and discusses the use of emerging technologies such as electrospinning and 3D printing to design new meshes. Furthermore, we discuss the impact and advantage of nano-/microstructured alternative meshes over commercial meshes with respect to their tissue integration performance. Considering the key challenges of current meshes, we discuss the potential of cell-based tissue engineering strategies to augment the new class of meshes to improve biocompatibility and immunomodulation. Finally, this review highlights the future direction in designing the new class of mesh to overcome the hurdles of foreign body rejection faced by the traditional meshes, in order to have safe and effective treatment for women in the long term.

The current urogynecological clinical meshes trigger unfavorable foreign body response which leads to graft failure in the long term. To overcome the present challenge, we applied a tissue engineering strategy using endometrial SUSD2+ mesenchymal stem cells (eMSCs) with high regenerative properties. This study delves deeper into foreign body response to SUSD2+ eMSC based degradable PLACL/gelatin nanofiber meshes using a mouse model targeted at understanding immunomodulation and mesh integration in the long term. Delivery of cells with nanofiber mesh provides a unique topography that enables entrapment of therapeutic cells for up to 6 weeks that promotes substantial cellular infiltration of host anti-inflammatory macrophages. As a result, degradation rate and tissue integration are highly impacted by eMSCs, revealing an unexpected level of implant integration over 6 weeks in vivo. From a clinical perspective, such immunomodulation may aid in overcoming the current challenges and provide an alternative to an unmet women's urogynecological health need.

The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in a xenogeneic rat skin wound repair model, but the mechanism remains unclear. In this study, we investigated the immunomodulatory effect of eMSC on the macrophage response to polyamide/gelatin composite mesh in an abdominal subcutaneous wound repair model in C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgamma null ) immunocompromised mice to determine whether responses differed in the absence of an adaptive immune system and NK cells. mCherry lentivirus-labelled eMSC persisted longer in NSG mice, inducing longer term paracrine effects. Inclusion of eMSC in the mesh reduced inflammatory cytokine (Il-1β, Tnfα) secretion, and in C57BL6 mice reduced CCR7+ M1 macrophages surrounding the mesh on day 3 and increased M2 macrophage marker mRNA (Arg1, Mrc1, Il10) expression at days 3 and 7. In NSG mice, these effects were delayed and only observed at days 7 and 30 in comparison with controls implanted with mesh alone. These results show that the differences in the immune status in the two animals directly affect the survival of xenogeneic eMSC which leads to differences in the short-term and long-term macrophage responses to implanted meshes.

Heart failure due to Myocardial Infarction (MI) remains the leading cause of death worldwide due to the inability of myocardial tissue to regenerate following infarction. Current therapies could only retard the progression of disease, but fails to bring functional improvement and cardiac regeneration. The present study analyzes the potentials of Poly(glycerol sebacate)/Fibrinogen (PGS/Fib) core/shell fibers as a structural support and initial entrapment of cells in an in vivo porcine model using echocardiography, histology, and immunohistochemistry. The echocardiography results showed the increased ejection fraction (EF) in PGS/Fib/VEGF/Cells compared with MI controls. The percentage increase in the End Diastolic Volume (EDV) dimension from post MI period to 4 weeks follow-up was the least in PGS/Fib/VEGF/Cells groups compared with MI and cell control group proving that the PGS/Fib/VEGF/Cells group restored the left ventricle (LV) function after MI, evident from the improvement in EF and prevention of LV enlargement. Further, immunohistochemistry results demonstrated that most of the transplanted mesenchymal stem cells (MSCs) within the PGS/Fib/VEGF scaffolds expressed cardiac marker proteins troponin and actinin and endothelial cell marker protein CD31 indicating differentiation of human bone marrow MSCs into cardiac cells and endothelial cells. The developed nanofibrous cardiac patch PGS/Fib/VEGF/Cells provides both functional and structural integrity to the infarcted myocardium and also serves as a suitable matrix for the entrapment of MSCs in clinical applications for cardiac tissue engineering.

The widespread use of synthetic transvaginal polypropylene mesh for treating Pelvic Organ Prolapse (POP) has been curtailed due to serious adverse effects highlighted in 2008 and 2011 FDA warnings and subsequent legal action. We are developing new synthetic mesh to deliver endometrial mesenchymal stem cells (eMSC) to improve mesh biocompatibility and restore strength to prolapsed vaginal tissue. Here we evaluated knitted polyamide (PA) mesh in an ovine multiparous model using transvaginal implantation and matched for the degree of POP. Polyamide mesh dip-coated in gelatin and stabilised with 0.5% glutaraldehyde (PA/G) were used either alone or seeded with autologous ovine eMSC (eMSC/PA/G), which resulted in substantial mesh folding, poor tissue integration and 42% mesh exposure in the ovine model. In contrast, a two-step insertion protocol, whereby the uncoated PA mesh was inserted transvaginally followed by application of autologous eMSC in a gelatin hydrogel onto the mesh and crosslinked with blue light (PA + eMSC/G), integrated well with little folding and no mesh exposure. The autologous ovine eMSC survived 30 days in vivo but had no effect on mesh integration. The stiff PA/G constructs provoked greater myofibroblast and inflammatory responses in the vaginal wall, disrupted the muscularis layer and reduced elastin fibres compared to PA + eMSC/G constructs. This study identified the superiority of a two-step protocol for implanting synthetic mesh in cellular compatible composite constructs and simpler surgical application, providing additional translational value.

An excessive foreign body response (FBR) has contributed to the adverse events associated with polypropylene mesh usage for augmenting pelvic organ prolapse surgery. Consequently, current biomaterial research considers the critical role of the FBR and now focuses on developing better biocompatible biomaterials rather than using inert implants to improve the clinical outcomes of their use. Tissue engineering approaches using mesenchymal stem cells (MSCs) have improved outcomes over traditional implants in other biological systems through their interaction with macrophages, the main cellular player in the FBR. The unique angiogenic, immunomodulatory and regenerative properties of MSCs have a direct impact on the FBR following biomaterial implantation. In this review, we focus on key aspects of the FBR to tissue-engineered MSC-based implants for supporting pelvic organs and beyond. We also discuss the immunomodulatory effects of the recently discovered endometrial MSCs on the macrophage response to new biomaterials designed for use in pelvic floor reconstructive surgery. We conclude with a focus on considerations in biomaterial design that take into account the FBR and will likely influence the development of the next generation of biomaterials for gynaecological applications.

Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration.

Aim: Myocardial infarction is caused after impairment of heart wall muscle following an immense cell loss and also when the myocardial tissue is lacking the inherent capacity to regenerate for normal functioning of myocardium. An immediate challenge in cardiac regeneration is to devise a strategy that leads to a reproducible degree of cardiac differentiation. We have speculated that ex vivo pretreatment of adipose-derived stem cells (ADSCs) using 5-azacytidine and a suitable patterned nanofibrous construct could lead to cardiomyogenic differentiation and results in superior biological and functional effects on cardiac regeneration of infarcted myocardium. Materials & methods: Polyglycerol sebacate/gelatin fibers were fabricated by core/shell electrospinning with polyglycerol sebacate as the core material and gelatin as the shell material. Patterning of the core/shell fibers to form orthogonal and looped buckled nanostructures was achieved. Results: Results demonstrated that the buckled fibers showing an orthogonal orientation and looped pattern had a Young’s modulus of approximately 3.59 ± 1.58 MPa and 2.07 ± 0.44 MPa, respectively, which was comparable to that of native myocardium. The ADSCs cultured on these scaffolds demonstrated greater expression of the cardiac-specific marker proteins actinin, troponin and connexin 43, as well as characteristic multinucleation as shown by immunocytochemical and morphological analysis, indicating complete cardiogenic differentiation of ADSCs. Conclusion: In the natural milieu, cardiomyogenic differentiation probably involves multiple signaling pathways and we have postulated that a buckled structure combination of chemical treatment and environment-driven strategy induces cardiogenic differentiation of ADSCs. The combination of patterned buckled fibrous structures with stem cell biology may prove to be a productive device for myocardial infarction. Original submitted 8 March 2012; Revised submitted 23 November 2012

Background Heart failure due to myocardial infarction remains the leading cause of death worldwide owing to the inability of myocardial tissue regeneration. The aim of this study is to develop a core/shell fibrous cardiac patch having desirable mechanical properties and biocompatibility to engineer the infarcted myocardium. Method We fabricated poly(glycerol sebacate)/fibrinogen (PGS/fibrinogen) core/shell fibers with core as elastomeric PGS provides suitable mechanical properties comparable to that of native tissue and shell as fibrinogen to promote cell–biomaterial interactions. The PGS/fibrinogen core/shell fibers and fibrinogen nanofibers were characterized by SEM, contact angle and tensile testing to analyze the fiber morphology, wettability, and mechanical properties of the scaffold. The cell–scaffold interactions were analyzed using isolated neonatal cardiomyocytes for cell proliferation, confocal analysis for the expression of marker proteins α-actinin, Troponin-T, β-myosin heavy chain and connexin 43 and SEM analysis for cell morphology. Results We observed PGS/fibrinogen core/shell fibers had a Young's modulus of about 3.28±1.7MPa, which was comparable to that of native myocardium. Neonatal cardiomyocytes cultured on these scaffolds showed normal expression of cardiac specific marker proteins α-actinin, Troponin, β-myosin heavy chain and connexin 43 to prove PGS/fibrinogen core/shell fibers have potential for cardiac tissue engineering. Conclusion Results indicated that neonatal cardiomyocytes formed predominant gap junctions and expressed cardiac specific marker proteins on PGS/fibrinogen core/shell fibers compared to fibrinogen nanofibers, indicating PGS/fibrinogen core/shell fibers may serve as a suitable cardiac patch for the regeneration of infarcted myocardium.

A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

Orthopedic treatments are amongst the most common cause of surgery and are responsible for a large share of global healthcare expenditures. Engineering materials that can hasten bone integration will improve the quality of life of millions of patients per year and reduce associated medical costs. Here, we present a novel hierarchical biomimetic coating that mimics the inorganic constituent of mammalian bones with the aim of improving osseointegration of metallic implants. We exploit the thermally-driven self-organization of metastable core-shell nanoparticles during their aerosol self-assembly to rapidly fabricate robust, ultra-porous nanoparticle networks (UNN) of crystalline hydroxyapatite (HAp). Comparative analysis of the response of osteoblast cells to the ultra-porous nanostructured HAp surfaces and to the spin coated HAp surfaces revealed superior osseointegrative properties of the UNN coatings with significant cell and filopodia infiltration. This flexible synthesis approach for the engineering of UNN HAp coatings on titanium implants provides a platform technology to study the bone-implant interface for improved osseointegration and osteoconduction.

Mimicking porous topography of natural extracellular matrix is advantageous for successful regeneration of damaged tissues or organs. Nanotechnology being one of the most promising and growing technology today shows an extremely huge potential in the field of tissue engineering. Nanofibrous structures that mimic the native extracellular matrix and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for skin, bone, vasculature, heart, cornea, nervous system, and other tissues. A range of novel biocomposite materials has been developed to enhance the bioactive or therapeutic properties of these nanofibrous scaffolds via surface modifications, including the immobilization of functional cell-adhesive ligands and bioactive molecules such as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic skin is avoided to reestablish physiological continuity and also to address the challenge of curing acute and chronic wounds, which remains as the area of exploration with various biomimetic approaches. Two-dimensional, three-dimensional scaffolds and stem cells are presently used as dermal regeneration templates for the treatment of full-thickness skin defects resulting from injuries and severe burns. The present review elaborates specifically on the fabrication of nanofibrous structured strategies for wound dressings, wound healing, and controlled release of growth factors for skin tissue regeneration.

Tissue engineering scaffolds for skin tissue regeneration is an ever expounding area of research, as the products that meet the necessary requirements are far and elite. The nanofibrous poly-L-lactic acid/poly-(α,β)-DL-aspartic acid/Collagen (PLLA/PAA/Col I&III) scaffolds were fabricated by electrospinning and characterized by SEM, contact angle and FTIR analysis for skin tissue regeneration. The cell-scaffold interactions were analyzed by cell proliferation and their morphology observed in SEM. The results showed that the cell proliferation was significantly increased (p≤0.05) in PLLA/PAA/Col I&III scaffolds compared to PLLA and PLLA/PAA nanofibrous scaffolds. The abundance and accessibility of adipose derived stem cells (ADSCs) may prove to be novel cell therapeutics for dermal tissue regeneration. The differentiation of ADSCs was confirmed using collagen expression and their morphology by CMFDA dye extrusion technique. The current study focuses on the application of PLLA/PAA/Col I&III nanofibrous scaffolds for skin tissue engineering and their potential use as substrate for the culture and differentiation of ADSCs. The objective for inclusion of a novel cell binding moiety like PAA was to replace damaged extracellular matrix and to guide new cells directly into the wound bed with enhanced proliferation and overall organization. This combinatorial epitome of PLLA/PAA/Col I&III nanofibrous scaffold with stem cell therapy to induce the necessary paracrine signalling effect would favour faster regeneration of the damaged skin tissues.

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

Pioneering research suggests various modes of cellular therapeutics and biomaterial strategies for myocardial tissue engineering. Despite several advantages, such as safety and improved function, the dynamic myocardial microenvironment prevents peripherally or locally administered therapeutic cells from homing and integrating of biomaterial constructs with the infarcted heart. The myocardial microenvironment is highly sensitive due to the nanoscale cues that it exerts to control bioactivities, such as cell migration, proliferation, differentiation, and angiogenesis. Nanoscale control of cardiac function has not been extensively analyzed in the field of myocardial tissue engineering. Inspired by microscopic analysis of the ventricular organization in native tissue, a scalable in-vitro model of nanoscale poly(L-lactic acid)-co -poly(ϵ -caprolactone)/collagen biocomposite scaffold is fabricated, with nanofibers in the order of 594 ± 56 nm to mimic the native myocardial environment for freshly isolated cardiomyocytes from rabbit heart, and the specifically underlying extracellular matrix architecture: this is done to address the specificity of the underlying matrix in overcoming challenges faced by cellular therapeutics. Guided by nanoscale mechanical cues provided by the underlying random nanofibrous scaffold, the tissue constructs display anisotropic rearrangement of cells, characteristic of the native cardiac tissue. Surprisingly, cell morphology, growth, and expression of an interactive healthy cardiac cell population are exquisitely sensitive to differences in the composition of nanoscale scaffolds. It is shown that suitable cell–material interactions on the nanoscale can stipulate organization on the tissue level and yield novel insights into cell therapeutic science, while providing materials for tissue regeneration.

World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive ‘remodelling’ and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium within vitro-engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.

Mesenchymal stem cells (MSC) are multipotent cells that differentiate into osteoblasts, myocytes, chondrocytes and adipocytes as well as insulin-producing cells. The mechanism underlying their in vivo differentiation is not clear and is thought to be caused by spontaneous cell fusion or factors present in the microenvironment. However, their ease of isolation, high 'ex-vivo' expansion potential and ability to differentiate into multiple lineages make them attractive tools for potential use in cell therapy. MSC have been isolated from several tissues, including bone/bone marrow, fat, Wharton's jelly, umbilical cord blood, placenta and pancreas. The 'immunosuppressive' property of human MSC makes them an important candidate for cellular therapy in allogeneic settings. Use of allogeneic MSC for repair of large defects may be an alternative to autologous and allogeneic tissue-grafting procedures. An allogeneic approach would enable MSC to be isolated from any donor, expanded and cryopreserved, providing a readily available source of progenitors for cell replacement therapy. Their immunomodulatory properties have raised the possibility of establishing allogeneic MSC banks for tissue regeneration. These facts are strongly reflected in the current exponential growth in stem cell research in the pharmaceutical and biotechnology communities. Current knowledge regarding the immunobiology and clinical application of MSC needs to be strengthened further to establish MSC as a safe and effective therapeutic tool in regenerative medicine. This paper discusses human MSC with particular reference to the expression of their surface markers, their role as immunomodulators and their multilineage differentiation potential and possible use in tissue regeneration and repair.

Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration.

Nanotechnology is an upcoming yet promising technology with respect to the development of well-established products. Nanofibers are potentially recent additions to materials in relation to tissue engineering (TE). Nanofiber-based scaffolds are being explored as scaffolds for TE applications. Electrospinning has developed into a versatile technique to fabricate polymeric nanofiber matrices, and the ability to incorporate bioactive therapeutic molecules without adversely affecting their structural integrity and biological activity using the mild electrospinning process has generated significant interest in polymeric nanofiber-based drug release patterns by changing the mode of encapsulation as well as by varying the matrix polymer. Scaffold composition and fabrication can be controlled to confirm desired properties and biofunctionalities. Interaction between the stem cells and nanofibers are crucial in a cell-scaffold matrix while using them for different TE applications. This chapter finally talks about the stem cell-nanofiber interactions in regenerative medicine and TE.

Every year, millions of people suffer from dermal wounds caused by heat, fire, chemicals, electricity, ultraviolet radiation or disease. Tissue engineering and nanotechnology have enabled the engineering of nanostructured materials to meet the current challenges in skin treatments owing to such rising occurrences of accidental damages, skin diseases and defects. The abundance and accessibility of adipose derived stem cells (ADSCs) may prove to be novel cell therapeutics for skin regeneration. The nanofibrous PVA/gelatin/azide scaffolds were then fabricated by electrospinning using water as solvent and allowed to undergo click reaction. The scaffolds were characterized by SEM, contact angle and FTIR. The cell-scaffold interactions were analyzed by cell proliferation and the results observed that the rate of cell proliferation was significantly increased (P ≤ 0.05) on PVA/gelatin/azide scaffolds compared to PVA/gelatin nanofibers. In the present study, manipulating the biochemical cues by the addition of an induction medium, in combination with environmental and physical factors of the culture substrate by functionalizing with click moieties, we were able to drive ADSCs into epidermal lineage with the development of epidermis-like structures, was further confirmed by the expression of early and intermediate epidermal differentiation markers like keratin and filaggrin. This study not only provides an insight into the design of a site-specific niche-like microenvironment for stem cell lineage commitment, but also sheds light on the therapeutic application of an alternative cell source-ADSCs, for wound healing and skin tissue reconstitution.

A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

Mimicking porous topography of natural extracellular matrix is advantageous for successful regeneration of damaged tissues or organs. Nanotechnology being one of the most promising and growing technology today shows an extremely huge potential in the field of tissue engineering. Nanofibrous structures that mimic the native extracellular matrix and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for skin, bone, vasculature, heart, cornea, nervous system, and other tissues. A range of novel biocomposite materials has been developed to enhance the bioactive or therapeutic properties of these nanofibrous scaffolds via surface modifications, including the immobilization of functional cell-adhesive ligands and bioactive molecules such as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic skin is avoided to reestablish physiological continuity and also to address the challenge of curing acute and chronic wounds, which remains as the area of exploration with various biomimetic approaches. Two-dimensional, three-dimensional scaffolds and stem cells are presently used as dermal regeneration templates for the treatment of full-thickness skin defects resulting from injuries and severe burns. The present review elaborates specifically on the fabrication of nanofibrous structured strategies for wound dressings, wound healing, and controlled release of growth factors for skin tissue regeneration.

The art and science of using biological tissue grafts from animal and human sources for various ailments is nascent. Various research groups around the world are actively investigating the potential prostheses of biological origin. Biological tissue grafts are rendered acellular through various methods of processing and fabrication before they are used for the specific purpose. The remainder is a scaffold that offers framework for host cellular repopulation and revascularization. Different methods of fixation have been explored over several decades to render the biological grafts suitable for use with or without extraction of cells. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize and deantigenize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Naturally derived biological scaffolds offer many mechanical, chemical and biological advantages over synthetic materials, and thus hold tremendous potential for use in tissue engineering therapies. Therefore the rationale of using biological grafts in usable forms is gaining importance in order to avoid unwanted chronic inflammatory reactions. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in various applications.