regeneration in humans regeneration in humans regeneration in humans is the regrowth of lost tissues or organs in response to injury. this is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury. numerous tissues and organs have been induced to regenerate. bladders have been 3d-printed in the lab since 1999. skin tissue can be regenerated in vivo or in vitro. other organs and body parts that have been procured to regenerate include: penis, fats, vagina, brain tissue, thymus, and a scaled down human heart. one goal of scientists is to induce full regeneration in more human organs. there are various techniques that can induce regeneration. by 2016, regeneration of tissue had been induced and operationalized by science. there are four main techniques: regeneration by instrument; regeneration by materials; regeneration by drugs and regeneration by in vitro 3d printing. history of human tissue in humans with non-injured tissues, the tissue naturally regenerates over time; by default, new available cells replace expended cells. for example, the body regenerates a full bone within ten years, while non-injured skin tissue is regenerated within two weeks. with injured tissue, the body usually has a different response. this emergency response usually involves building a degree of scar tissue over a time period longer than a regenerative response, as has been proven clinically and via observation. there are many more historical and nuanced understandings about regeneration processes. in full thickness wounds that are under 2mm, regeneration generally occurs before scarring. in 2008, in full thickness wounds over 3mm, it was found that a wound needed a material inserted in order to induce full tissue regeneration. whereas 3rd degree burns heal slowly by scarring, in 2016 it was known that full thickness fractional photothermolysis holes heal without scarring. up to 40% of full thickness skin can be removed without scarring in an area, in a fractional pattern via coring of tissue. some human organs and tissues regenerate rather than simply scar, as a result of injury. these include the liver, fingertips, and endometrium. more information is now known regarding the passive replacement of tissues in the human body, as well as the mechanics of stem cells. advances in research have enabled the induced regeneration of many more tissues and organs than previously thought possible. the aim for these techniques is to use these techniques in the near future for the purpose of regenerating any tissue type in the human body. regeneration techniques regenerating a human ear using a scaffold by 2016, regeneration had been operationalised and induced by four main techniques: regeneration by instrument; regeneration by materials; regeneration by 3d printing; and regeneration by drugs. by 2016, regeneration by instrument, regeneration by materials and by regeneration drugs had been generally operationalised in vivo (inside living tissues). whilst by 2016, regeneration by 3d printing had been generally operationalised by in vitro (inside the lab) in order to be built and prepare tissue for transplantation. by instrument a cut by a knife or a scalpel generally scars, though a piercing by a needle does not. in 1976, a 3 by 3cm scar on a non-diabetic was regenerated by insulin injections and the researchers, highlighting earlier research, argued that the insulin was regenerating the tissue. the anecdotal evidence also highlighted that a syringe was one of two variables that helped bring regeneration of the arm scar. the syringe was injected into the four quadrants three times a day for eighty-two days. after eighty-two days, after many consecutive injections, the scar was resolved and it was noted no scar was observable by the human eye. after seven months the area was checked again and it was once again noted that no scar could be seen. in 1997, it was proven that wounds created with an instrument that are under 2mm can heal scar free, but larger wounds that are larger than 2mm healed with a scar. in 2013, it was proven in pig tissue that full thickness micro columns of tissue, less than 0.5mm in diameter could be removed and that the replacement tissue, was regenerative tissue, not scar. the tissue was removed in a fractional pattern, with over 40% of a square area removed; and all of the fractional full thickness holes in the square area healed without scarring. in 2016 this fractional pattern technique was also proven in human tissue. with materials generally, humans can regenerate injured tissues in vivo for limited distances of up to 2mm. the further the wound distance is from 2mm the more the wound regeneration will need inducement. by 2009, via the use of materials, a max induced regeneration could be achieved inside a 1 cm tissue rupture. bridging the wound, the material allowed cells to cross the wound gap; the material then degraded. this technology was first used inside a broken urethra in 1996. in 2012, using materials, a full urethra was restored in vivo. macrophage polarization is a strategy for skin regeneration. macrophages are differentiated from circulating monocytes. macrophages display a range of phenotypes varying from the m1, pro-inflammatory type to the m2, pro-regenerative type. material hydrogels polarise macrophages into the key m2 regenerative phenotype in vitro. in 2017, hydrogels provided full regeneration of skin, with hair follicles, after partial excision of scars in pigs and after full thickness wound incisions in pigs. by 3d printing in 2009, the regeneration of hollow organs and tissues with a long diffusion distance, was a little more challenging. therefore, to regenerate hollow organs and tissues with a long diffusion distance, the tissue had to be regenerated inside the lab, via the use of a 3d printer. various tissues that have been regenerated by in vitro 3d printing include: the first organ ever induced and made in the lab was the bladder, which was created in 1999. by 2014, there had been various tissues regenerated by the 3d printer and these tissues included: muscle, vagina, penis and the thymus. in 2014, a conceptual human lung was first bioengineered in the lab. in 2015, the lab robustly tested its technique and regenerated a pig lung. the pig lung was then successfully transplanted into a pig without the use of immunosuppressive drugs. in 2015, researchers developed a proof of principle biolimb inside a laboratory; they also estimated that it would be at least a decade for any testing of limbs in humans. the limb demonstrated fully functioning skin, muscles, blood vessels and bones. in april 2019, researchers 3d printed a human heart. the prototype heart was made by human stem cells but only to the size of a rabbit's heart. in 2019, the researchers hoped to one day place a scaled up version of the heart inside humans. gradations of complexity level 1level 2level 3level 4 skinblood vesselbladderheart muscleliver nailspancreas penis with printing tissues, by 2012, there were four accepted standard levels of regenerative complexity that were acknowledged in various academic institutions: level one, flat tissue like skin was the simplest to recreate; level two was tubular structures such as blood vessels; level three was hollow non-tubular structures; level four was solid organs, which were by far the most complex to recreate due to the vascularity. in 2012, within 60 days it was possible, inside the lab, to grow tissue the size of half a postage stamp to the size of a football field. most cell types could be grown and expanded outside of the body, with the exception of the liver, nerve and pancreas, as these tissue types need stem cell populations. with drugs lipoatrophy is the localised loss of fat in tissue. it is common in diabetics who use conventional insulin injection treatment. in 1949, a much more pure form of insulin was, instead of causing lipoatrophy, shown to regenerate the localised loss of fat after injections in to diabetics. in 1984, it was shown that different insulin injections have different regenerative responses with regards to creating skin fats in the same person. it was shown in the same body that conventional forms of insulin injections cause lipoatrophy and highly purified insulin injections cause lipohypertrophy. in 1976, the regenerative response was shown to work in a non-diabetic after a 3 x 3cm lipoatrophic arm scar was treated with pure monocomponent porcine soluble insulin. a syringe injected insulin under the skin equally in the four quadrants of the defect. to layer four units of insulin evenly into the base of the defect, each quadrant of the defect received one unit of insulin three times a day, for eighty-two days. after eighty-two days of consecutive injections the defect regenerated to normal tissue. in 2016, scientists could transform a skin cell into any other tissue type via the use of drugs. the technique was noted as safer than genetic reprogramming which, in 2016, was a concern medically. the technique, used a cocktail of chemicals and enabled efficient on site regeneration without any genetic programming. in 2016, it was hoped to one day use this drug to regenerate tissue at the site of tissue injury. in 2017, scientists could turn many cell types (such as brain and heart) into skin. research for research about induced regeneration, see § induced regeneration. scientists found leprosy-causing bacteria viably regenerate and rejuvenate the liver in its armadillos hosts, which may enable novel human therapies based on knowledge or components gained from naturally evolved organisms or capabilities. naturally regenerating appendages and organs heart cardiomyocyte necrosis activates an inflammatory response that serves to clear the injured myocardium from dead cells, and stimulates repair, but may also extend injury. research suggests that the cell types involved in the process play an important role. namely monocyte-derived macrophages tend to induce inflammation while inhibiting cardiac regeneration, while tissue resident macrophages may help restoration of tissue structure and function. endometrium the endometrium after the process of breakdown via the menstruation cycle, re-epithelializes swiftly and regenerates. though tissues with a non-interrupted morphology, like non-injured soft tissue, completely regenerate consistently; the endometrium is the only human tissue that completely regenerates consistently after a disruption and interruption of the morphology. fingers in may 1932, l. h. mckim published a report describing the regeneration of an adult digit-tip following amputation. a house surgeon in the montreal general hospital underwent amputation of the distal phalanx to stop the spread of an infection. in less than one month following surgery, x-ray analysis showed the regrowth of bone while macroscopic observation showed the regrowth of nail and skin. this is one of the earliest recorded examples of adult human digit-tip regeneration. studies in the 1970s showed that children up to the age of 10 or so who lose fingertips in accidents can regrow the tip of the digit within a month provided their wounds are not sealed up with flaps of skin – the de facto treatment in such emergencies. they normally will not have a fingerprint, and if there is any piece of the finger nail left it will grow back as well, usually in a square shape rather than round. in august 2005, lee spievack, then in his early sixties, accidentally sliced off the tip of his right middle finger just above the first phalanx. his brother, dr. alan spievack, was researching regeneration and provided him with powdered extracellular matrix, developed by dr. stephen badylak of the mcgowan institute of regenerative medicine. mr. spievack covered the wound with the powder, and the tip of his finger re-grew in four weeks. the news was released in 2007. ben goldacre has described this as "the missing finger that never was", claiming that fingertips regrow and quoted simon kay, professor of hand surgery at the university of leeds, who from the picture provided by goldacre described the case as seemingly "an ordinary fingertip injury with quite unremarkable healing" a similar story was reported by cnn. a woman named deepa kulkarni lost the tip of her little finger and was initially told by doctors that nothing could be done. her personal research and consultation with several specialists including badylak eventually resulted in her undergoing regenerative therapy and regaining her fingertip. kidney regenerative