Why tissue engineering

The combination of all bone cells in an in vitro bone model is challenging and will be of utmost importance to better understand bone cell biology, i. The heart is a complex organ containing a wide variety of cell types e. The activity of heart cells is regulated by an internal control system, sensitive to both external and systemic cues Benam et al.

Such a complex architecture is supported by a well-defined 3D framework based on fibrous proteins e. This 3D ECM network is responsible for the typical organization of cardiac muscle fibers along a preferred direction, which results in the peculiar mechanical properties and cell functions characterizing the myocardium. As a consequence of the key role of ECM architecture on heart development and function, the ideal in vitro cardiac tissue model should accurately reproduce heart 3D anisotropic structure and vasculature in both healthy and pathological state, control and properly guide cell—cell and cell—ECM interactions and regulate cell fate and functions Mathur et al.

In pathological conditions, after a myocardial infarction or an ischemia, as well as with aging, the myocardium undergoes a remodeling process characterized by loss of functional cardiomyocytes, hypertrophy of the remaining cells and fibrosis, that result in a progressive alteration of heart mechanical properties i. Consequently, an in vitro model of pathological cardiac tissue should accurately recapitulate cardiac changes in terms of structure, mechanical properties, cell density, and functions.

Such an approach is essential in the design of suitable in vitro models for i drug development and testing cardiotoxicity is a major cause of withdrawal of newly commercialized drugs Ferri et al. Both animal models and 2D cell cultures fail to accurately and fully reproduce human physiology in healthy and pathological conditions, as well as in young and aged states. For example, human CMs show significantly different electrophysiological properties with respect to the murine ones: mice heart rate at rest is about 10 times that of humans, while QT segment in humans is about four times that of mice Passier et al.

As a consequence of the multifactorial nature of cardiovascular diseases, a different animal model should be used depending on the investigated pathology [e. An appropriate selection of the model would be essential to avoid failing of many research findings upon translation to humans. On the other hand, traditional 2D in vitro cell cultures do not properly replicate the complexity of the in vivo environment and fail to maintain cardiac cells in culture for a long time, thus limiting the possibility of long-term studies.

In this context, bioengineered healthy or pathologic heart tissue constructs can i exhibit genotypic and phenotypic properties more similar to native environment, ii reproduce cardiac tissue architecture, iii promote cell—cell and cell—ECM interactions, stimulating the formation of gap junctions, iv favor tissue maturation and the expression of a phenotypic profile similar to that of mature cardiomyocytes, and v allow accurate functional parameters measurements Benam et al.

Early developed heart models were based on immortalized or primary cells extracted from several species, such as chickens, mice, and rats, that did not accurately reproduce the physiology of the human heart, as previously mentioned, and failed in the reproduction of several pathological conditions, such as reduced conductivity, fibrosis, and scar formation Harding et al.

Recent advancements in genome-editing technologies have opened the way to the possibility to engineer hiPSC genome by introducing the gene mutations associated with a specific heart disease, thus allowing the generation of pathological CMs to be used for disease modeling Wang et al.

Do date, hiPSC-derived CMs have been successfully employed to model several rhythm-associated diseases [e. Moreover, hiPSCs open the way to the development of patient-specific in vitro models that could be exploited in the future to better understand disease onset and progression, and specially to test the effects of drugs and therapies on each patient. Nevertheless, an important issue still needs to be addressed: CMs derived from stem cells are usually small in size and immature, showing a gene expression profile more similar to fetal CMs than adult cardiac muscle cells, and exhibit reduced contractility Itzhaki et al.

Since several topographical, electrical, mechanical, biochemical, and cellular cues actively contribute to heart development and CM maturation in vivo , efforts are currently directed to the exploitation of engineering methods e. As an example, properly surface-patterned substrates have been recently coupled with biochemical cues to enhance maturation of hiPSC-derived CMs Ribeiro et al.

Figure 3. Upon differentiation toward the cardiac phenotype hiPSC-CMs , the two-dimensional cardiac tissue model was designed by plating the cells onto fibronectin-coated glass coverslips.

Arrows identify single and multiple premature beats Itzhaki et al. Two-dimensional in vitro models based on cell seeding on substrate surfaces functionalized with cardiac ECM proteins e. For instance, aligned murine CMs showed calcium handling, action potentials and conductivity more similar to adult mouse heart, with respect to the same cells cultivated on randomly oriented substrates Thomas et al. The capability of such models to recapitulate the spatial heterogeneity and conductivity of cardiac tissue was successfully exploited to study pathologies of the electrical conduction system of the myocardium Thomas et al.

The same approach was exploited to design a model of the border zone the interface between healthy cardiac tissue and an infarcted area Chang et al. In vivo , the border zone shows a non-uniform anisotropic structure resulting from the remodeling cascade activated by a myocardial infarction, which makes this tissue easily susceptible to arrhythmias.

The developed model was based on human skeletal myotubes simulating the typical fibrosis of the border zone cocultured with neonatal rat ventricular CMs recapitulating the non-uniform anisotropic architecture of the border zone on fibronectin-coated coverslips. This system successfully modeled the onset of reentrant arrhythmias in the border zone, allowing the study of the effects of several drugs on this pathology and the explanation of the scarce effects of sodium channel blockers.

However, in vitro 2D models fail to completely reproduce the mechanical contraction and architecture typical of the heart, thus hindering the ability of cells to interact and exert forces on each other. With the final aim of overcoming these drawbacks, several research groups designed 3D models recapitulating both healthy and pathological cardiac tissue.

Scaffolds designed and fabricated for such applications should be biocompatible, exhibit a 3D structure with interconnected pores, which promote cell homing, nutrient and oxygen supply and waste removal, and reproduce both the structural and mechanical properties of the native cardiac tissue Silvestri et al.

The literature reports on the fabrication of 3D scaffolds based on both natural and synthetic polymers and their blends by either conventional or advanced technologies.

A widely investigated technology consists in cardiomyocyte loading into biodegradable natural polymers, e. Matrigel was often used to enhance cell viability and adhesion due to its composition rich in growth factors and ECM components Mathur et al. Moreover, it was successfully blended with other natural polymers, such as fibrinogen and thrombin, or collagen type I, and seeded with neonatal rat CMs or stem cell-derived CMs to design models for drug screening Hansen et al.

The developed substrates were cultured in four different situations: normal glucose without or with the addition of insulin N and NI, respectively , and high glucose without or with the addition of insulin H and HI, respectively. Results demonstrated that, in diabetic conditions i. Insulin administration enhanced cell viability, contractility and normalized gene expression in both NI and HI models.

On the other hand, administration of anti-diabetic drugs showed anti-apoptotic effects and enhanced excitability in bioengineered constructs cultured according to H conditions, but did not affect gene expression. Such ischemic conditions turned out inhibited by treating the models with cardioprotective drugs, e.

Synthetic polymers are promising alternatives to ECM-derived ones, due to their high versatility, repeatability and controlled composition. The literature reports the exploitation of several synthetic polymers for the design of both cardiac patches and in vitro models.

The most suitable synthetic polymers for such applications are elastomers, e. Bursacet al. A model of LQTS was successfully developed by Ma and colleagues by seeding CMs derived from iPSCs from pathological patients on anisotropic scaffolds produced by two-photon initiated polymerization Ma et al.

Healthy cardiac tissue models were also fabricated by seeding iPSC-derived CMs isolated from healthy individuals. The models were validated by assessing their differences in terms of contractility, QT segment duration, tissue structure and response to several molecules, e.

Aratyn-Schaus et al. To this aim, two cell microtissues were designed by seeding mouse CMs, recapitulating native myocardium, and CMs derived from iPSCs and ESCs, modeling newly formed cells, on soft gels coated with fibronectin, according to a well-defined pattern, mimicking the striated structure and mechanical properties of the heart. The mechanical coupling between the two microtissues was thoroughly studied, demonstrating that newly formed CMs couple with native cells to support synchronous contraction, but the reduced force transmission between them may hamper the complete recovery of contractility.

In , the design of cardiac microtissues has been further enhanced by Giacomelli and coworkers that have recently developed a human-derived model recapitulating the cardiomyocyte—endothelium crosstalk, which is responsible for the regulation of heart dimension, oxygen supply, and growth factor secretion and has poorly been considered so far in both cardiac patch and engineered model design Giacomelli et al.

A 3D scaffold-free cardiac tissue model based on multiple cell type coculture has been recently created for the first time by Rogozhnikov et al. Such an approach could open the way to a new era in cardiac TE, allowing the development of high cell density constructs showing spontaneous synchronous beating throughout the entire matrix without the application of electrical cues and efficient cell—cell and cell—ECM crosstalk.

The pancreas is an organ characterized by two distinct functional portions: the exocrine and the endocrine pancreas. The functional unit of the exocrine pancreas is the pancreatic acinar cell, which has the main functions of synthesis, storage and secretion of digestive enzymes.

These enzymes are normally activated in the duodenum, meanwhile acute pancreatitis occurs when they are prematurely activated within the pancreatic acinar cell. The endocrine portion of the pancreas is constituted by small clusters of cells called islets of Langerhans.

Moreover, several minor hormones are synthetized from pancreatic islet cells. Hormone secretion is modulated by nervous signals and, thanks to a high vascularization, hormones secreted by islets have ready access to the circulation McManus and Mitchell, Type II diabetes is the most diffused form of diabetes Moller, ; Stumvoll et al.

Due to the high relevance of these diseases Nanji and Shapiro, , pancreas studies have been mostly focused on the islets of Langerhans. Moreover, islets are a key focus of type II diabetic drug efficacy testing Li et al.

Mice constitute the most investigated animal model in pancreas research. In , Kim and colleagues studies Kharouta et al. These species differences have raised concerns regarding the use of mice prototypic islets, highlighting the need to develop more realistic islet models. The first challenge in engineering pancreatic islets is the isolation and purification of viable and functional islets.

This response is mainly due to the loss of cell—cell communication Ilieva et al. Moreover, when cultured in vitro , islet cells undergo necrotic cell death predominantly in the islet core, as a consequence of inadequate oxygen supply due to the high metabolic demands and islet size Andersson, ; Ilieva et al.

In order to reach a successful strategy to preserve islet cell survival and functions, several studies have focused on restoring the ECM environment. From this point of view, tissue-engineered scaffolds represent a valid alternative to effectively support pancreatic cell culture and secretion of hormones and polypeptides, while bioreactors are useful tools to provide the required perfusion conditions to prevent in vitro cell necrosis Bentsi-Barnes et al.

Synthetic polymeric scaffolds have been extensively studied for islet culture and transplantation. In particular, polyester scaffolds were fabricated from lactide and glycolide monomers and copolymers, using different fabrication techniques Blomeier et al. Mao et al. In another study, rat islet cells were seeded on porous polyglycolic acid PGA fiber scaffold Synthecon Inc. In contrast to the scaffold-free control group, islet cells cultured on scaffolds exhibited improved morphology, viability, and increased insulin secretion.

Functionalization of synthetic polymeric scaffolds with bioactive molecules, such as ECM components, has been proposed to mimic the ECM environment. Salvay et al. Those scaffolds showed good viability, insulin production and vessel density within the transplanted islets. Although synthetic polymeric scaffolds have been successfully employed according to the classic TE approach, they are not adequate to replicate pancreas mechanical properties, which play a key role in the design of valuable tissue and organ models.

In fact, the pancreas is a non-linear viscoelastic soft tissue. The shear stiffness of healthy pancreatic tissue was found to be in the range of 1—2 kPa Wex et al.

On the other hand, porous scaffolds used in the previously mentioned studies did not resemble pancreas morphology and a justification for the architecture selection is not generally reported. It should be observed that further investigations are necessary to understand how pathologic conditions affect the mechanical properties of pancreatic tissue, such as in chronic pancreatitis Janssen et al.

In the diagnosis of chronic pancreatitis, it is presumed that pancreatic shear stiffness is proportional to the degree of fibrosis Ziol et al. There is a lack of studies regarding the mechanical characterization of the scaffolds proposed, which is particularly important to elucidate the different behavior of healthy and pathological tissues. Therefore, pathological and physiological models may be achieved taking into account this consideration.

Li et al. The copolymerization of PLL with PEG was designed to introduce positive charges on the gel surface, allowing the absorption of ECM components derived from rat pancreatic decellularized matrix and inducing cell—ECM interactions. Figure 4. Reprinted with permission from Li et al. Among natural-derived hydrogels, alginate has been successfully used in the classic approach of pancreatic TE, where microencapsulation of the islets is performed to preserve them from immune mediated destruction after transplantation Lim and Sun, ; Korbutt et al.

Thus, alginate hydrogels could represent a valid scaffold for the development of pancreatic in vitro models. However, the major limitation of alginate microbeads is the high permeability to a range of small molecules, which can damage or destroy the encapsulated islets Van Schilfgaarde and De Vos, To overcome these problems a perm-selective coating with PLL or Poly- l -Ornithine has been proposed, since these polyamino acids firmly bind to alginate, thereby restricting the permeability of alginate-based microcapsules Thu et al.

In contrast, the capsule must be permeable to nutrients, metabolites and hormones to allow islet survival. It was observed that a reduction in capsule size improves the diffusion of nutrients to the islets. Omer et al. Nevertheless, with reduction in capsule size an increase in the number of capsules containing protruding islets was observed, leading to a higher number of capsules affected by an inflammatory response.

Decreasing the islet density in alginate can solve this problem. Not only the size but also the morphology of the microcapsules is an important parameter: spherical microcapsules are necessary for long-term functions Hobbs et al. In order to overcome problems related to the supply of oxygen and nutrients, Li et al. The system supported islet viability and functions in vitro over a 7-day culture period. The model displayed a high sensitivity in responding to two typical anti-diabetic drugs tolbutamide and GLP-1 and drug dosages over conventional 2D and 3D static models.

Hou et al. The simulated microgravity was achieved through a rotary cell culture system Cameron et al. After 5 days in culture in this bioreactor, the islet grafts were transplanted into leg muscles of diabetic rats to observe their functions and morphology.

The results demonstrated that islets cultured under dynamic conditions in the scaffolds exhibited better viability and insulin production compared to those cultured in static condition, confirming the importance of both scaffolds and dynamic culture in the mimesis of the native environment and the maintenance of cell viability and functions. This approach can be translated to the design of an in vitro functional islet model. Pancreas TE is mainly focused on the encapsulation of Langerhans islets for further transplantation.

The requisites that should be met in that case are different from those required in the development of an in vitro model of the islets themselves. However, there are some common requisites, such as the challenging maintenance of the islet cell viability and functions after isolation. The research works surveyed in this review reported a progress in the design of biomimetic constructs able to support both cell survival and functions in culture; however, more engineered systems are needed to develop valuable pancreas models.

Such a goal is challenging, due to the complexity of this organ. Forthcoming pancreatic models need to mimic the native tissue in all the mechanical, topographical and chemical aspects, as well as in the set of physiological cues that characterize the complex pancreatic environment. The models developed for the pancreas are few, indicating that the design of a model for such complicate organ requires further efforts and a closer collaboration between different fields of research.

The liver is the largest visceral organ in humans, playing a wide and complex array of vital functions, ranging from metabolic and regulatory activities to protein synthesis and organism defense processes Mazzoleni and Steimberg, The liver is characterized by a complex array of vasculature, endothelial cells and parenchymal cells hepatocytes, hepatocyte precursors, stellate cells, epithelial cells and fibroblasts Lorenzini and Andreone, ; Kazemnejad, Liver ECM plays a pivotal role on hepatocyte viability, proliferation, migration and functions Mazzoleni and Steimberg, In fact, as a consequence of their structural and functional polarization, hepatocytes need well-defined cell—cell and cell—ECM interactions to remain viable, proliferate and exert their activities.

From a structural point of view, the liver is characterized by a complex, highly organized architecture composed of a tessellating system of hexagonal constructs lobules , fundamental for maintaining hepatic functions Patzer and Gerlach, ; Mazzoleni and Steimberg, In pathological conditions of fibrosis, liver architecture is distorted because of ECM proteins accumulation and the formation of fibrous scar tissue, which induce an increase in tissue stiffness Bataller and Brenner, Advanced fibrosis results in cirrhosis that causes dysfunctions and is responsible for hepatic insufficiency Bataller and Brenner, At present, the procedure leading to the clinical application of newly developed drugs requires more than 10 years and a high economical investment about one billion euros Adams and Brantner, Currently, no animal model fully recapitulates all the hepatic and extrahepatic features of healthy and pathological liver: first, some hepatic diseases do not exist in rodents, and second, animals can show higher or lower susceptibility to drugs compared to humans Delire et al.

A wide variability is usually observed between humans and animal models in terms of drug pathogenicity, time of action and effects Starkel and Leclercq, In this context, there is increasing interest in developing more reliable in vitro liver models, able to imitate liver functions in pharmacokinetics, thus allowing a more accurate drug testing as well as compliance to 3Rs principle.

At the same time, a thorough investigation of hepatic functions and pathologies e. The simplest in vitro liver models consisting of hepatic sub-cellular fractions e. Nevertheless, they fail in the mimesis of cell—cell and cell—ECM interactions, essential for hepatocyte viability and functions, resulting in cell dedifferentiation and loss of the majority of their phenotypic properties, including their drug-metabolizing capacity, thus hampering their application in drug testing Mazzoleni and Steimberg, ; Mueller et al.

However, the capability to maintain liver native functions for only few days about three days under conventional cell culture conditions, together with tissue shortage and its high variability, have limited the establishment of 2D primary hepatocyte cell culture and consequently the use of these cells in the development of liver models Guillouzo and Guguen-Guillouzo, ; Mazzoleni and Steimberg, ; Mueller et al.

Primary rodent hepatocytes have been widely exploited in drug testing and drug-drug interaction studies, but the translation of the obtained results to humans is made difficult by differences in metabolism among the two species Uehara et al.

On the other hand, human immortalized hepatic cancer cell lines, such as HepG2, show unlimited availability and maintain certain liver functions, e. However, they do not exhibit drug-metabolizing capacities, which can cause inaccurate drug toxicity testing. In several studies, immortalized hepatic cells turned out suitable models for parent compound toxicity studies and in the assessment of cell polarity and chemotherapy resistance Hoekstra et al.

Hepatocytes derived from stem cells embryonic- and adult tissue-derived stem cells exhibit promising liver-specific features, such as the expression of cytochrome P PYP enzymes enzymes involved in the metabolism of many molecules and the formation of structures similar to the bile canaliculi.

Moreover, they provide a highly available hepatocyte source from different donors, thus enhancing reproducibility and allowing the study of individual-specific drug toxicity. However, the secretion of liver-specific proteins and enzymes, as well as the expression of CYP enzymes and membrane transporters, need to be comparable to those of native hepatocytes Mueller et al.

Perfused livers and liver slices show the advantage of retaining the 3D architecture, cell—cell and cell—ECM interactions of the native organ, but they do not allow long-term studies since necrosis occurs within 48—72 h and metabolic enzymes levels decrease in 6—72 hours Mueller et al. Therefore, the use of biomaterial-based 3D liver tissue models is a rapidly expanding field, devoted to the design of novel smart constructs, accurately mimicking liver tissue in its healthy and pathological state, from a morphological, mechanical and biochemical point of view.

For instance, Mazza et al. The procedure was followed by repopulation with human liver-derived cells, thus confirming that the optimized decellularization procedure did not damage the liver tissue features, essential for cell homing, migration and proliferation Mazza et al. Similar results were also reported by Uygun and colleagues, which also demonstrated that the preservation of the native vasculature results in enhanced cell engraftment, survival and maintenance of hepatocyte functions albumin secretion, urea synthesis and cytochrome P similar to normal liver Uygun et al.

The 3D structure resulting from decellularization is also an efficient substrate for stem cell differentiation: Wang et al. Among synthetic polymers, biocompatible and biodegradable polyesters, e.

For instance, several studies reported the hepatic differentiation of bone marrow-derived MSCs Kazemnejad et al. Moreover, Vinci et al. This study demonstrated that cell density and cell—cell interactions are strongly influenced by substrate architecture, while cell metabolism is mainly regulated by nutrient supply and interstitial-like flow Vinci et al. Indeed, albumin and urea production rates turned out greatly augmented during dynamic cell culture in a low-shear, high-flow bioreactor.

The presence of integrin-binding sites and specific sequences in natural polymers can be exploited to activate the desired cell behavior and signaling cascades. Dvir-Ginzberg and colleagues reported the capability of alginate scaffolds to maintain hepatocyte functions during 1-week culture time Dvir-Ginzberg et al. Furthermore, alginate scaffolds showed ability to induce hepatic differentiation of bone marrow-derived stem cells in the presence of specific growth factors Lin et al. Hyaluronate-based scaffolds promoted hepatic functions of liver cells as a consequence of the signaling pathways activated by cell binding to the material Zavan et al.

Similarly, chitosan properly modified with specific polysaccharide residues can bind liver cells, thus improving their functions and metabolic activity Li et al.

Moreover, doping natural polymer-based scaffolds with conducting polymers seems to positively influence hepatocyte adhesion and proliferation, enhancing the electrical communication among cells Rad et al.

Induced pluripotent stem cells have recently arisen as promising candidates for the design of patient-specific hepatic models. In detail, Ma et al. Figure 5. Three-dimensional 3D printed hepatic lobule models. Reprinted with permission from Ma et al. From a morphological point of view, hiPSC-derived hepatocytes, human vein endothelial cells and adipose tissue-derived stem cells were embedded in a 3D hexagonal structure, according to well-defined patterns finely mimicking their localization in the native lobules.

On the other hand, from a functional point of view, high expression of liver-specific genes, increased metabolic activity, and enhanced cytochrome P induction were observed. Therefore, the designed 3D tri-culture model showed improved morphological, phenotypic and functional properties, thus opening the way to the clinical introduction of in vitro models for personalized in vitro drug screening and disease study.

Nowadays, TE approaches are widely investigated for the development of 3D in vitro models of healthy and pathological tissues and organs. The results summarized in this review demonstrate that the TE approach can be successfully employed in the development of 3D models of many human tissues and organs, such as bone, heart, pancreas, and liver. This interdisciplinary field is rapidly developing and advancing. The main limitation deals with the identification of the proper cell sources for model design, and in particular with the difficulty to isolate human primary cells and culture them in vitro for long-term experiments, since primary cells show high sensitivity to culture conditions and progressive loss of differentiation potential after a low number of passages in culture.

In the last decade, the most promising novelty in the cell biology field is the discovery of iPSCs. Reprogramming adult cells to embryonic-like states has innumerable potential applications in regenerative medicine and drug development. Three-dimensional cell surrounding environment exerts a synergistic role in guiding cell fate and behavior; therefore, a fine replication in vitro of the in vivo environment in terms of both architecture and mechanical properties is mandatory.

Furthermore, the development of a biomimetic environment is a key aspect in the long-term culture of any type of cells. In this scenario, bringing together new advances in material engineering, microfabrication techniques and microfluidics is gaining more and more importance.

The advancement in biomaterials science, including the design and development of new synthetic copolymers, ceramic and glass—ceramics, bioartificial blends of natural and synthetic materials, can be exploited to finely tune the chemical, thermal, mechanical and surface properties of the scaffold-forming materials Baino and Vitale-Brovarone, ; Sionkowska, ; Sartori et al.

The progress of these custom-made materials allows to accurately recapitulate the bulk properties of the native tissue at different health levels.

Furthermore, emergent advanced scaffold fabrication methods are gaining more and more interest as they allow the fabrication of more reproducible scaffolds with a highly controlled process. These include a good control of pore size and interconnection, which facilitates gas diffusion, nutrient supply and waste removal, leading to a degree of vascularization of the constructs similar to native tissues.

Specifically, techniques based on rapid prototyping, bioprinting, organ printing and bottom-up approaches are emerging as promising tools, with the potential to overcome the drawbacks of conventional approaches, and providing a step forward the clinical validation of 3D in vitro engineered tissue models as a consequence of their high versatility, temporal and spatial control Elbert, ; Xu et al. Finally, to increase the industrial scalability of the models and allow high-throughput applications, recent developments in cell biology, TE, microfluidics and biomaterials are now being integrated in microfluidically perfused organ-on-chip models Baker, ; Huh et al.

Some relevant in vitro tissue models have recently started to appear in the literature, improving the confidence that, in the future, the design of 3D models of high quality and relevance can significantly reduce the number of animals used in research as well as the failure of drug-screening methodologies.

All the authors agree on the final version to be published. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Part A 14, — Davidson, M. Stem cell-derived liver cells for drug testing and disease modeling. What are tissue engineering and regenerative medicine? A mini bioengineered human liver that can be implanted into mice. Source: Sangeeta Bhatia, MIT Tissue engineering evolved from the field of biomaterials development and refers to the practice of combining scaffolds, cells, and biologically active molecules into functional tissues.

What is Tissue Engineering? Source: Northwestern University Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. A biomaterial made from pigs' intestines which can be used to heal wounds in humans.

When moistened, the material, which is called SIS, is flexible and easy to handle. Source: Stephen Badylak, University of Pittsburgh. Controlling stem cells through their environment: For many years, scientists have searched for ways to control how stems cells develop into other cell types, in the hopes of creating new therapies. Two NIBIB researchers have grown pluripotent cells—stem cells that have the ability to turn into any kind of cell—in different types of defined spaces and found that this confinement triggered very specific gene networks that determined the ultimate fate for the cells.

Most other medical research on pluripotent stem cells has focused on modifying the combination of growth solutions in which the cells are placed. The discovery that there is a biomechanical element to controlling how stem cells transform into other cell types is an important piece of the puzzle as scientists try to harness stems cells for medical uses.

Research Topics Tissue engineering Tissue Regeneration. Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Archer, R. Why tissue engineering needs process engineering. Nat Biotechnol 23, — Download citation. Issue Date : 01 November Anyone you share the following link with will be able to read this content:.

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