Editing Tissue engineering (section)

== Tissue culture ==

In many cases, creation of functional tissues and biological structures ''in vitro'' requires extensive [[cell culture|culturing]] to promote survival, growth and inducement of functionality. In general, the basic requirements of cells must be maintained in culture, which include [[oxygen]], [[pH]], [[humidity]], [[temperature]], [[nutrient]]s and [[osmotic pressure]] maintenance.{{cn|date=April 2025}}

Tissue engineered cultures also present additional problems in maintaining culture conditions. In standard cell culture, [[diffusion]] is often the sole means of nutrient and metabolite transport. However, as a culture becomes larger and more complex, such as the case with engineered organs and whole tissues, other mechanisms must be employed to maintain the culture, such as the creation of capillary networks within the tissue.{{cn|date=April 2025}}

[[File:Bioreaktor.JPG|right|thumb|upright|Bioreactor for cultivation of vascular grafts]]

Another issue with tissue culture is introducing the proper factors or stimuli required to induce functionality. In many cases, simple maintenance culture is not sufficient. [[Growth factor]]s, [[hormone]]s, specific metabolites or nutrients, chemical and physical stimuli are sometimes required. For example, certain cells respond to changes in oxygen tension as part of their normal development, such as [[chondrocyte]]s, which must adapt to low oxygen conditions or [[Hypoxia (medical)|hypoxia]] during skeletal development. Others, such as endothelial cells, respond to [[shear stress]] from fluid flow, which is encountered in [[blood vessel]]s. Mechanical stimuli, such as pressure pulses seem to be beneficial to all kind of cardiovascular tissue such as heart valves, blood vessels or pericardium.{{cn|date=April 2025}}

=== Bioreactors ===

{{Main|Bioreactor}}

In tissue engineering, a bioreactor is a device that attempts to simulate a physiological environment in order to promote cell or tissue growth in vitro. A physiological environment can consist of many different parameters such as temperature, pressure, oxygen or carbon dioxide concentration, or osmolality of fluid environment, and it can extend to all kinds of biological, chemical or mechanical stimuli. Therefore, there are systems that may include the application of forces such as electromagnetic forces, mechanical pressures, or fluid pressures to the tissue. These systems can be two- or three-dimensional setups. Bioreactors can be used in both academic and industry applications. General-use and application-specific bioreactors are also commercially available, which may provide static chemical stimulation or a combination of chemical and mechanical stimulation.{{cn|date=April 2025}}

Cell [[Cell proliferation|proliferation]] and [[Cellular differentiation|differentiation]] are largely influenced by mechanical<ref>{{cite journal | vauthors = Maul TM, Chew DW, Nieponice A, Vorp DA | title = Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation | journal = Biomechanics and Modeling in Mechanobiology | volume = 10 | issue = 6 | pages = 939–53 | date = December 2011 | pmid = 21253809 | pmc = 3208754 | doi = 10.1007/s10237-010-0285-8 }}</ref> and biochemical<ref>{{cite journal | vauthors = Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR | display-authors = 6 | title = Multilineage potential of adult human mesenchymal stem cells | journal = Science | volume = 284 | issue = 5411 | pages = 143–47 | date = April 1999 | pmid = 10102814 | doi = 10.1126/science.284.5411.143 | bibcode = 1999Sci...284..143P }}</ref> cues in the surrounding [[extracellular matrix]] environment. Bioreactors are typically developed to replicate the specific physiological environment of the tissue being grown (e.g., flex and fluid shearing for heart tissue growth).<ref name="CM and PNIPAAm">{{cite journal | vauthors = Lee EL, von Recum HA | title = Cell culture platform with mechanical conditioning and nondamaging cellular detachment | journal = Journal of Biomedical Materials Research. Part A | volume = 93 | issue = 2 | pages = 411–18 | date = May 2010 | pmid = 20358641 | doi = 10.1002/jbm.a.32754 }}</ref> This can allow specialized cell lines to thrive in cultures replicating their native environments, but it also makes bioreactors attractive tools for culturing [[stem cell]]s. A successful stem-cell-based bioreactor is effective at expanding stem cells with uniform properties and/or promoting controlled, reproducible differentiation into selected mature cell types.<ref>{{cite journal | vauthors = King JA, Miller WM | title = Bioreactor development for stem cell expansion and controlled differentiation | journal = Current Opinion in Chemical Biology | volume = 11 | issue = 4 | pages = 394–98 | date = August 2007 | pmid = 17656148 | pmc = 2038982 | doi = 10.1016/j.cbpa.2007.05.034 }}</ref>

There are a variety of [[bioreactors]] designed for 3D cell cultures. There are small plastic cylindrical chambers, as well as glass chambers, with regulated internal humidity and moisture specifically engineered for the purpose of growing cells in three dimensions.<ref name="mc2biotek.com">{{cite web|url=http://www.mc2biotek.com/3d-tissue-culture/the-3d-prototissue-system/|archive-url=https://web.archive.org/web/20120528202009/http://www.mc2biotek.com/3d-tissue-culture/the-3d-prototissue-system/|url-status=dead|archive-date=28 May 2012|title=MC2 Biotek – 3D Tissue Culture – The 3D ProtoTissue System™}}</ref> The bioreactor uses [[Biological activity|bioactive]] synthetic materials such as [[polyethylene terephthalate]] membranes to surround the spheroid cells in an environment that maintains high levels of nutrients.<ref name="Prestwich, GD 2008 pp. 139">{{cite journal | vauthors = Prestwich GD | title = Evaluating drug efficacy and toxicology in three dimensions: using synthetic extracellular matrices in drug discovery | journal = Accounts of Chemical Research | volume = 41 | issue = 1 | pages = 139–48 | date = January 2008 | pmid = 17655274 | doi = 10.1021/ar7000827 }}</ref><ref>{{cite journal | vauthors = Friedrich J, Seidel C, Ebner R, Kunz-Schughart LA | title = Spheroid-based drug screen: considerations and practical approach | journal = Nature Protocols | volume = 4 | issue = 3 | pages = 309–24 | year = 2009 | pmid = 19214182 | doi = 10.1038/nprot.2008.226 | s2cid = 21783074 }}</ref> They are easy to open and close, so that cell spheroids can be removed for testing, yet the chamber is able to maintain 100% humidity throughout.<ref name="Marx, Vivien 2013">{{cite journal | vauthors = Marx V | title = Cell culture: a better brew | journal = Nature | volume = 496 | issue = 7444 | pages = 253–58 | date = April 2013 | pmid = 23579682 | doi = 10.1038/496253a | s2cid = 4399610 | bibcode = 2013Natur.496..253M | doi-access = free }}</ref> This humidity is important to achieve maximum cell growth and function. The bioreactor chamber is part of a larger device that rotates to ensure equal cell growth in each direction across three dimensions.<ref name="Marx, Vivien 2013"/>

QuinXell Technologies now under [http://www.quintechlifesciences.com Quintech Life Sciences] from [[Singapore]] has developed a bioreactor known as the [https://www.quintechlifesciences.com/home/tisxell/ TisXell Biaxial Bioreactor] which is specially designed for the purpose of tissue engineering. It is the first bioreactor in the world to have a spherical glass chamber with [[biaxial]] rotation; specifically to mimic the rotation of the fetus in the womb; which provides a conducive environment for the growth of tissues.<ref>{{cite journal | vauthors = Zhang ZY, Teoh SH, Chong WS, Foo TT, Chng YC, Choolani M, Chan J | title = A biaxial rotating bioreactor for the culture of fetal mesenchymal stem cells for bone tissue engineering | journal = Biomaterials | volume = 30 | issue = 14 | pages = 2694–704 | date = May 2009 | pmid = 19223070 | doi = 10.1016/j.biomaterials.2009.01.028 }}</ref>

Multiple forms of mechanical stimulation have also been combined into a single bioreactor. Using gene expression analysis, one academic study found that applying a combination of cyclic strain and ultrasound stimulation to pre-osteoblast cells in a bioreactor accelerated matrix maturation and differentiation.<ref>{{cite journal | vauthors = Kang KS, Lee SJ, Lee HS, Moon W, Cho DW | title = Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts | journal = Experimental & Molecular Medicine | volume = 43 | issue = 6 | pages = 367–73 | date = June 2011 | pmid = 21532314 | pmc = 3128915 | doi = 10.3858/emm.2011.43.6.040 }}</ref> The technology of this combined stimulation bioreactor could be used to grow bone cells more quickly and effectively in future clinical stem cell therapies.<ref>{{cite book| vauthors = Rosser J, Thomas DJ | chapter = 10 – Bioreactor processes for maturation of 3D bioprinted tissue|date= January 2018 | title = 3D Bioprinting for Reconstructive Surgery|pages=191–215| veditors = Thomas DJ, Jessop ZM, Whitaker IS |publisher=Woodhead Publishing|language=en|isbn=978-0-08-101103-4 }}</ref>

[[MC2 Biotek]] has also developed a bioreactor known as ProtoTissue<ref name="mc2biotek.com"/> that uses [[gas exchange]] to maintain high oxygen levels within the cell chamber; improving upon previous bioreactors, since the higher oxygen levels help the cell grow and undergo normal [[cell respiration]].<ref>{{cite journal | vauthors = Griffith LG, Swartz MA | title = Capturing complex 3D tissue physiology in vitro | journal = Nature Reviews. Molecular Cell Biology | volume = 7 | issue = 3 | pages = 211–24 | date = March 2006 | pmid = 16496023 | doi = 10.1038/nrm1858 | s2cid = 34783641 }}</ref>

Active areas of research on bioreactors includes increasing production scale and refining the physiological environment, both of which could improve the efficiency and efficacy of bioreactors in research or clinical use. Bioreactors are currently used to study, among other things, cell and tissue level therapies, cell and tissue response to specific physiological environment changes, and development of disease and injury.{{cn|date=April 2025}}

=== Long fiber generation ===
In 2013, a group from the [[University of Tokyo]] developed cell laden fibers up to a meter in length and on the order of 100&nbsp;[[μm]] in size.<ref name="pmid23542870">{{cite journal | vauthors = Onoe H, Okitsu T, Itou A, Kato-Negishi M, Gojo R, Kiriya D, Sato K, Miura S, Iwanaga S, Kuribayashi-Shigetomi K, Matsunaga YT, Shimoyama Y, Takeuchi S | display-authors = 6 | title = Metre-long cell-laden microfibres exhibit tissue morphologies and functions | journal = Nature Materials | volume = 12 | issue = 6 | pages = 584–90 | date = June 2013 | pmid = 23542870 | doi = 10.1038/nmat3606 | bibcode = 2013NatMa..12..584O }}</ref> These fibers were created using a [[microfluidic device]] that forms a double coaxial laminar flow. Each 'layer' of the microfluidic device (cells seeded in [[Extracellular matrix|ECM]], a hydrogel sheath, and finally a calcium chloride solution). The seeded cells culture within the hydrogel sheath for several days, and then the sheath is removed with viable cell fibers. Various cell types were inserted into the ECM core, including [[myocytes]], [[endothelial cells]], nerve cell fibers, and [[epithelial cell]] fibers. This group then showed that these fibers can be woven together to fabricate tissues or organs in a mechanism similar to textile [[weaving]]. Fibrous morphologies are advantageous in that they provide an alternative to traditional scaffold design, and many organs (such as muscle) are composed of fibrous cells.

===Bioartificial organs===
{{main|Bioartificial organ}}

An artificial organ is an engineered device that can be extra corporeal or implanted to support impaired or failing organ systems.<ref name=":5">{{cite journal | vauthors = Wang X | title = Bioartificial Organ Manufacturing Technologies | journal = Cell Transplantation | volume = 28 | issue = 1 | pages = 5–17 | date = January 2019 | pmid = 30477315 | pmc = 6322143 | doi = 10.1177/0963689718809918 }}</ref> Bioartificial organs are typically created with the intent to restore critical biological functions like in the replacement of diseased hearts and lungs, or provide drastic quality of life improvements like in the use of engineered skin on burn victims.<ref name=":5" /> While some examples of bioartificial organs are still in the research stage of development due to the limitations involved with creating functional organs, others are currently being used in clinical settings experimentally and commercially.<ref>{{cite journal | vauthors = Sawa Y, Matsumiya G, Matsuda K, Tatsumi E, Abe T, Fukunaga K, Ichiba S, Kishida A, Kokubo K, Masuzawa T, Myoui A, Nishimura M, Nishimura T, Nishinaka T, Okamoto E, Tokunaga S, Tomo T, Tsukiya T, Yagi Y, Yamaoka T | display-authors = 6 | title = Journal of Artificial Organs 2017: the year in review : Journal of Artificial Organs Editorial Committee | journal = Journal of Artificial Organs | volume = 21 | issue = 1 | pages = 1–7 | date = March 2018 | pmid = 29426998 | pmc = 7102331 | doi = 10.1007/s10047-018-1018-5 }}</ref>

==== Lung ====
[[Extracorporeal membrane oxygenation]] (ECMO) machines, otherwise known as heart and lung machines, are an adaptation of [[cardiopulmonary bypass]] techniques that provide heart and lung support.<ref name=":6">{{cite journal | vauthors = Chauhan S, Subin S | title = Extracorporeal membrane oxygenation, an anesthesiologist's perspective: physiology and principles. Part 1 | journal = Annals of Cardiac Anaesthesia | volume = 14 | issue = 3 | pages = 218–29 | date = 2011-09-01 | pmid = 21860197 | doi = 10.4103/0971-9784.84030 | doi-access = free }}</ref> It is used primarily to support the lungs for a prolonged but still temporary timeframe (1–30 days) and allow for recovery from reversible diseases.<ref name=":6" /> [[Robert Bartlett (surgeon)|Robert Bartlett]] is known as the father of ECMO and performed the first treatment of a newborn using an ECMO machine in 1975.<ref>{{Cite web|date=2017-06-20|title=How did ECMO get started?|url=https://uihc.org/health-topics/how-did-ecmo-get-started|access-date=2020-12-04|website=University of Iowa Hospitals & Clinics|language=en}}</ref>

'''Skin'''

Tissue-engineered skin is a type of bioartificial organ that is often used to treat burns, diabetic foot ulcers, or other large wounds that cannot heal well on their own. Artificial skin can be made from autografts, allografts, and xenografts. Autografted skin comes from a patient's own skin, which allows the dermis to have a faster healing rate, and the donor site can be re-harvested a few times. Allograft skin often comes from cadaver skin and is mostly used to treat burn victims. Lastly, xenografted skin comes from animals and provides a temporary healing structure for the skin. They assist in dermal regeneration, but cannot become part of the host skin.<ref name="auto1"/> Tissue-engineered skin is now available in commercial products. Integra, originally used to only treat burns, consists of a collagen matrix and chondroitin sulfate that can be used as a skin replacement. The chondroitin sulfate functions as a component of proteoglycans, which helps to form the extracellular matrix.<ref>{{Cite web|title=Chondroitin sulfate is a component of Integra® Dermal Regeneration Template |url=https://fdocuments.us/document/chondroitin-sulfate-chondroitin-sulfate-is-a-component-of-integra-dermal-regeneration.html|access-date=2020-12-05|website=fdocuments.us|language=en}}</ref> Integra can be repopulated and revascularized while maintaining its dermal collagen architecture, making it a bioartificial organ<ref>{{Cite web|url=https://www.integralife.com/file/general/1525975889.pdf|title=Integra|accessdate=13 March 2023}}</ref> Dermagraft, another commercial-made tissue-engineered skin product, is made out of living fibroblasts. These fibroblasts proliferate and produce growth factors, collagen, and ECM proteins, that help build granulation tissue.<ref>{{Cite web|title=Dermagraft Human Fibroblast-derived Dermal Substitute|url=https://dermagraft.com/|access-date=2020-12-05|website=dermagraft.com}}</ref>

==== Heart ====

Since the number of patients awaiting a heart transplant is continuously increasing over time, and the number of patients on the waiting list surpasses the organ availability,<ref>{{cite journal | vauthors = Colvin M, Smith JM, Hadley N, Skeans MA, Uccellini K, Lehman R, Robinson AM, Israni AK, Snyder JJ, Kasiske BL | display-authors = 6 | title = OPTN/SRTR 2017 Annual Data Report: Heart | journal = American Journal of Transplantation | volume = 19 | issue = Suppl 2 | pages = 323–403 | date = February 2019 | pmid = 30811894 | doi = 10.1111/ajt.15278 | s2cid = 73510324 | doi-access = free | hdl = 2027.42/172019 | hdl-access = free }}</ref> artificial organs used as replacement therapy for terminal heart failure would help alleviate this difficulty.  Artificial hearts are usually used to bridge the heart transplantation or can be applied as replacement therapy for terminal heart malfunction.<ref>{{cite book | vauthors = Smith PA, Cohn WE, Frazier OH |chapter =Chapter 7 – Total artificial hearts |doi = 10.1016/B978-0-12-810491-0.00007-2 | title =Mechanical Circulatory and Respiratory Support |publisher=Academic Press |pages=221–44 |date=1 January 2018}}</ref> The total artificial heart (TAH), first introduced by Dr. Vladimir P. Demikhov in 1937,<ref>{{cite journal | vauthors = Khan S, Jehangir W | title = Evolution of Artificial Hearts: An Overview and History | journal = Cardiology Research | volume = 5 | issue = 5 | pages = 121–25 | date = October 2014 | pmid = 28348709 | pmc = 5358116 | doi = 10.14740/cr354w }}</ref> emerged as an ideal alternative. Since then it has been developed and improved as a mechanical pump that provides long-term circulatory support and replaces diseased or damaged heart ventricles that cannot properly pump the blood, restoring thus the pulmonary and systemic flow.<ref>{{cite journal | vauthors = Melton N, Soleimani B, Dowling R | title = Current Role of the Total Artificial Heart in the Management of Advanced Heart Failure | journal = Current Cardiology Reports | volume = 21 | issue = 11 | pages = 142 | date = November 2019 | pmid = 31758343 | doi = 10.1007/s11886-019-1242-5 | s2cid = 208212152 }}</ref> Some of the current TAHs include AbioCor, an FDA-approved device that comprises two artificial ventricles and their valves, and does not require subcutaneous connections, and is indicated for patients with biventricular heart failure. In 2010 SynCardia released the portable freedom driver that allows patients to have a portable device without being confined to the hospital.<ref>{{cite journal | vauthors = Cook JA, Shah KB, Quader MA, Cooke RH, Kasirajan V, Rao KK, Smallfield MC, Tchoukina I, Tang DG | display-authors = 6 | title = The total artificial heart | journal = Journal of Thoracic Disease | volume = 7 | issue = 12 | pages = 2172–80 | date = December 2015 | pmid = 26793338 | pmc = 4703693 | doi = 10.3978/j.issn.2072-1439.2015.10.70 }}</ref>

==== Kidney ====
While kidney transplants are possible, renal failure is more often treated using an artificial kidney.<ref name = "Tasnim_2010">{{cite journal | vauthors = Tasnim F, Deng R, Hu M, Liour S, Li Y, Ni M, Ying JY, Zink D | display-authors = 6 | title = Achievements and challenges in bioartificial kidney development | journal = Fibrogenesis & Tissue Repair | volume = 3 | issue = 14 | pages = 14 | date = August 2010 | pmid = 20698955 | doi = 10.1186/1755-1536-3-14 | pmc = 2925816 | doi-access = free }}</ref> The first artificial kidneys and the majority of those currently in use are extracorporeal, such as with hemodialysis, which filters blood directly, or peritoneal dialysis, which filters via a fluid in the abdomen.<ref name = "Tasnim_2010" /><ref name = "Humes_2014">{{cite journal | vauthors = Humes HD, Buffington D, Westover AJ, Roy S, Fissell WH | title = The bioartificial kidney: current status and future promise | journal = Pediatric Nephrology | volume = 29 | issue = 3 | pages = 343–51 | date = March 2014 | pmid = 23619508 | doi = 10.1007/s00467-013-2467-y | s2cid = 19376597 }}</ref> In order to contribute to the biological functions of a kidney such as producing metabolic factors or hormones, some artificial kidneys incorporate renal cells.<ref name = "Tasnim_2010" /><ref name = "Humes_2014" /> There has been progress in the way of making these devices smaller and more transportable, or even [https://pharm.ucsf.edu/kidney implantable ]. One challenge still to be faced in these smaller devices is countering the limited volume and therefore limited filtering capabilities.<ref name = "Tasnim_2010" />

Bioscaffolds have also been introduced to provide a framework upon which normal kidney tissue can be regenerated. These scaffolds encompass natural scaffolds (e.g., decellularized kidneys,<ref>{{cite journal | vauthors = Su J, Satchell SC, Shah RN, Wertheim JA | title = Kidney decellularized extracellular matrix hydrogels: Rheological characterization and human glomerular endothelial cell response to encapsulation | journal = Journal of Biomedical Materials Research. Part A | volume = 106 | issue = 9 | pages = 2448–2462 | date = September 2018 | pmid = 29664217 | pmc = 6376869 | doi = 10.1002/jbm.a.36439 }}</ref> collagen hydrogel,<ref>{{cite journal | vauthors = Lee SJ, Wang HJ, Kim TH, Choi JS, Kulkarni G, Jackson JD, Atala A, Yoo JJ | display-authors = 6 | title = In Situ Tissue Regeneration of Renal Tissue Induced by Collagen Hydrogel Injection | journal = Stem Cells Translational Medicine | volume = 7 | issue = 2 | pages = 241–250 | date = February 2018 | pmid = 29380564 | pmc = 5788870 | doi = 10.1002/sctm.16-0361 }}</ref><ref>{{Cite journal | vauthors = Wu H, Zhang R, Hu B, He Y, Zhang Y, Cai L, Wang L, Wang G, Hou H, Qiu X |date=December 2021 |title=A porous hydrogel scaffold mimicking the extracellular matrix with swim bladder derived collagen for renal tissue regeneration |journal=Chinese Chemical Letters |language=en |volume=32 |issue=12 |pages=3940–3947 |doi=10.1016/j.cclet.2021.04.043|s2cid=235570487 }}</ref> or silk fibroin<ref>{{cite journal | vauthors = Mou X, Shah J, Bhattacharya R, Kalejaiye TD, Sun B, Hsu PC, Musah S | title = A Biomimetic Electrospun Membrane Supports the Differentiation and Maturation of Kidney Epithelium from Human Stem Cells | journal = Bioengineering | volume = 9 | issue = 5 | pages = 188 | date = April 2022 | pmid = 35621466 | pmc = 9137565 | doi = 10.3390/bioengineering9050188 | doi-access = free }}</ref>), synthetic scaffolds (e.g., poly[lactic-co-glycolic acid]<ref>{{cite journal | vauthors = Lih E, Park KW, Chun SY, Kim H, Kwon TG, Joung YK, Han DK | title = Biomimetic Porous PLGA Scaffolds Incorporating Decellularized Extracellular Matrix for Kidney Tissue Regeneration | journal = ACS Applied Materials & Interfaces | volume = 8 | issue = 33 | pages = 21145–21154 | date = August 2016 | pmid = 27456613 | doi = 10.1021/acsami.6b03771 }}</ref><ref>{{cite journal | vauthors = Burton TP, Callanan A | title = A Non-woven Path: Electrospun Poly(lactic acid) Scaffolds for Kidney Tissue Engineering | journal = Tissue Engineering and Regenerative Medicine | volume = 15 | issue = 3 | pages = 301–310 | date = June 2018 | pmid = 30603555 | pmc = 6171675 | doi = 10.1007/s13770-017-0107-5 }}</ref> or other polymers), or a combination of two or more natural and synthetic scaffolds. These scaffolds can be implanted into the body either without cell treatment or after a period of stem cell seeding and incubation. In vitro and In vivo studies are  being conducted to compare and optimize the type of scaffold and to assess whether cell seeding prior to implantation adds to the viability, regeneration and effective function of the kidneys. A recent systematic review and meta-analysis compared the results of published animal studies and identified that improved outcomes are reported with the use of hybrid (mixed) scaffolds and cell seeding;<ref>{{cite journal | vauthors = Mirmoghtadaei M, Khaboushan AS, Mohammadi B, Sadr M, Farmand H, Hassannejad Z, Kajbafzadeh AM | title = Kidney tissue engineering in preclinical models of renal failure: a systematic review and meta-analysis | journal = Regenerative Medicine | volume = 17 | issue = 12 | pages = 941–955 | date = December 2022 | pmid = 36154467 | doi = 10.2217/rme-2022-0084 | s2cid = 252543376 }}</ref> however, the meta-analysis of these results were not in agreement with the evaluation of descriptive results from the review. Therefore, further studies involving larger animals and novel scaffolds, and more transparent reproduction of previous studies are advisable.

===Biomimetics===
{{main|Biomimetics}}
{{tone|section|date=December 2019}}
Biomimetics is a field that aims to produce materials and systems that replicate those present in nature.<ref name="hwang">{{cite journal | vauthors = Hwang J, Jeong Y, Park JM, Lee KH, Hong JW, Choi J | title = Biomimetics: forecasting the future of science, engineering, and medicine | journal = International Journal of Nanomedicine | volume = 10 | pages = 5701–13 | date = 8 September 2015 | pmid = 26388692 | pmc = 4572716 | doi = 10.2147/IJN.S83642 | doi-access = free }}</ref> In the context of tissue engineering, this is a common approach used by engineers to create materials for these applications that are comparable to native tissues in terms of their structure, properties, and biocompatibility. Material properties are largely dependent on physical, structural, and chemical characteristics of that material. Subsequently, a biomimetic approach to system design will become significant in material integration, and a sufficient understanding of biological processes and interactions will be necessary. Replication of biological systems and processes may also be used in the synthesis of bio-inspired materials to achieve conditions that produce the desired biological material. Therefore, if a material is synthesized having the same characteristics of biological tissues both structurally and chemically, then ideally the synthesized material will have similar properties. This technique has an extensive history originating from the idea of using natural phenomenon as design inspiration for solutions to human problems. Many modern advancements in technology have been inspired by nature and natural systems, including aircraft, automobiles, architecture, and even industrial systems. Advancements in nanotechnology initiated the application of this technique to micro- and [[nano-scale]] problems, including tissue engineering. This technique has been used to develop synthetic bone tissues, vascular technologies, scaffolding materials and integration techniques, and functionalized nanoparticles.<ref name=hwang/>