of these early startups were often not very clear and did not present a path to long term profitability. government sponsors were more restrained in their funding as tissue engineering was considered a high-risk investment. in the uk the market got off to a slower start even though the regulations on stem cell research were not strict as well. this is mainly due to more investors being less willing to invest in these new technologies which were considered to be high-risk investments. another problem faced by british companies was getting the nhs to pay for their products. this especially because the nhs runs a cost-effectiveness analysis on all supported products. novel technologies often do not do well in this respect. in japan, the regulatory situation was quite different. first cell cultivation was only allowed in a hospital setting and second academic scientists employed by state-owned universities were not allowed outside employment until 1998. moreover, the japanese authorities took longer to approve new drugs and treatments than there us and european counterparts. for these reasons in the early days of the japanese market, the focus was mainly on getting products that were already approved elsewhere in japan and selling them. contrary to the us market the early actors in japan were mainly big firms or sub-companies of such big firms, such as j-tec, menicon and terumo, and not small startups. after regulatory changes in 2014, which allowed cell cultivation outside of a hospital setting, the speed of research in japan increased and japanese companies also started to develop their own products. crash soon after the big boom, the first problems started to appear. there were problems getting products approved by the fda and if they got approved there were often difficulties in getting insurance providers to pay for the products and getting it accepted by health care providers. for example, organogenesis ran into problems marketing its product and integrating its product in the health system. this partially due to the difficulties of handling living cells and the increased difficulties faced by physicians in using these products over conventional methods. another example would be advanced tissue sciences dermagraft skin product which could not create a high enough demand without reimbursements from insurance providers. reasons for this were $4000 price-tag and the circumstance that additionally advanced tissue sciences struggled to get their product known by physicians. the above examples demonstrate how companies struggled to make profit. this, in turn, lead investors to lose patience and stopping further funding. in consequence, several tissue engineering companies such as organogenesis and advanced tissue sciences filed for bankruptcy in the early 2000s. at this time, these were the only ones having commercial skin products on the market. reemergence the technologies of the bankrupt or struggling companies were often bought by other companies which continued the development under more conservative business models. examples of companies who sold their products after folding were curis and intercytex. many of the companies abandoned their long-term goals of developing fully functional organs in favor of products and technologies that could turn a profit in the short run. examples of these kinds of products are products in the cosmetic and testing industry. in other cases such as in the case of advanced tissue sciences, the founders started new companies. in the 2010s the regulatory framework also started to facilitate faster time to market especially in the us as new centres and pathways were created by the fda specifically aimed at products coming from living cells such as the center for biologics evaluation and research. the first tissue engineering products started to get commercially profitable in the 2010s. regulation in europe, regulation is currently split into three areas of regulation: medical devices, medicinal products, and biologics. tissue engineering products are often of hybrid nature, as they are often composed of cells and a supporting structure. while some products can be approved as medicinal products, others need to gain approval as medical devices. derksen explains in her thesis that tissue engineering researchers are sometimes confronted with regulation that does not fit the characteristics of tissue engineering. new regulatory regimes have been observed in europe that tackle these issues. an explanation for the difficulties in finding regulatory consensus in this matter is given by a survey conducted in the uk. the authors attribute these problems to the close relatedness and overlap with other technologies such as xenotransplantation. it can therefore not be handled separately by regulatory bodies. regulation is further complicated by the ethical controversies associated with this and related fields of research (e.g. stem cells controversy, ethics of organ transplantation). the same survey as mentioned above shows on the example of autologous cartilage transplantation that a specific technology can be regarded as 'pure' or 'polluted' by the same social actor. two regulatory movements are most relevant to tissue engineering in the european union. these are directive 2004/23/ec on standards of quality and safety for the sourcing and processing of human tissues which was adopted by the european parliament in 2004 and a proposed human tissue-engineered products regulation. the latter was developed under the auspices of the european commission dg enterprise and presented in brussels in 2004.