Editing Silk (section)

====Biocompatibility====
Biocompatibility, i.e., to what level the silk will cause an immune response, is a critical issue for biomaterials. The issue arose during its increasing clinical use. Wax or silicone is usually used as a coating to avoid fraying and potential immune responses<ref name="Rockwood-2011" /> when silk fibers serve as suture materials. Although the lack of detailed characterization of silk fibers, such as the extent of the removal of sericin, the surface chemical properties of coating material, and the process used, make it difficult to determine the real immune response of silk fibers in literature, it is generally believed that sericin is the major cause of immune response. Thus, the removal of sericin is an essential step to assure biocompatibility in biomaterial applications of silk. However, further research fails to prove clearly the contribution of sericin to inflammatory responses based on isolated sericin and sericin based biomaterials.<ref>{{cite journal |last1=Zhang|first1=Yaopeng|last2=Yang|first2=Hongxia|last3=Shao|first3=Huili|last4=Hu|first4=Xuechao|date=2010-05-05|title=Antheraea pernyiSilk Fiber: A Potential Resource for Artificially Biospinning Spider Dragline Silk|journal=Journal of Biomedicine and Biotechnology|language=en|volume=2010|pages=683962|doi=10.1155/2010/683962|pmc=2864894|pmid=20454537|doi-access=free}}</ref> In addition, silk fibroin exhibits an inflammatory response similar to that of tissue culture plastic in vitro<ref>{{cite journal |last1=Wray|first1=Lindsay S.|last2=Hu|first2=Xiao|last3=Gallego|first3=Jabier|last4=Georgakoudi|first4=Irene|last5=Omenetto|first5=Fiorenzo G.|last6=Schmidt|first6=Daniel|last7=Kaplan|first7=David L.|date=2011-10-01|title=Effect of processing on silk-based biomaterials: Reproducibility and biocompatibility|journal=Journal of Biomedical Materials Research Part B: Applied Biomaterials|language=en|volume=99B|issue=1|pages=89–101|doi=10.1002/jbm.b.31875|pmc=3418605|pmid=21695778}}</ref><ref name="Meinel-2005">{{cite journal |last1=Meinel|first1=Lorenz|last2=Hofmann|first2=Sandra|last3=Karageorgiou|first3=Vassilis|last4=Kirker-Head|first4=Carl|last5=McCool|first5=John|last6=Gronowicz|first6=Gloria|last7=Zichner|first7=Ludwig|last8=Langer|first8=Robert|last9=Vunjak-Novakovic|first9=Gordana|date=2005-01-01|title=The inflammatory responses to silk films in vitro and in vivo|journal=Biomaterials|volume=26|issue=2|pages=147–155|doi=10.1016/j.biomaterials.2004.02.047|pmid=15207461}}</ref> when assessed with human mesenchymal [[stem cell]]s (hMSCs) or lower than collagen and PLA when implant rat MSCs with silk fibroin films in vivo.<ref name="Meinel-2005" /> Thus, appropriate degumming and sterilization will assure the biocompatibility of silk fibroin, which is further validated by in vivo experiments on rats and pigs.<ref>{{cite journal |last1=Fan|first1=Hongbin|last2=Liu|first2=Haifeng|last3=Toh|first3=Siew L.|last4=Goh|first4=James C.H.|title=Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model|journal=Biomaterials|volume=30|issue=28|pages=4967–4977|doi=10.1016/j.biomaterials.2009.05.048|pmid=19539988|year=2009}}</ref> There are still concerns about the long-term safety of silk-based biomaterials in the human body in contrast to these promising results. Even though silk sutures serve well, they exist and interact within a limited period depending on the recovery of wounds (several weeks), much shorter than that in tissue engineering. Another concern arises from biodegradation because the biocompatibility of silk fibroin does not necessarily assure the biocompatibility of the decomposed products. In fact, different levels of immune responses<ref>{{cite journal |last1=Minoura|first1=N.|last2=Aiba|first2=S.|last3=Higuchi|first3=M.|last4=Gotoh|first4=Y.|last5=Tsukada|first5=M.|last6=Imai|first6=Y.|date=1995-03-17|title=Attachment and growth of fibroblast cells on silk fibroin|journal=Biochemical and Biophysical Research Communications|volume=208|issue=2|pages=511–516|pmid=7695601|doi=10.1006/bbrc.1995.1368}}</ref><ref>{{cite journal |last1=Gellynck|first1=Kris|last2=Verdonk|first2=Peter C. M.|last3=Van Nimmen|first3=Els|last4=Almqvist|first4=Karl F.|last5=Gheysens|first5=Tom|last6=Schoukens|first6=Gustaaf|last7=Van Langenhove|first7=Lieva|last8=Kiekens|first8=Paul|last9=Mertens|first9=Johan|date=2008-11-01|title=Silkworm and spider silk scaffolds for chondrocyte support|journal=Journal of Materials Science: Materials in Medicine|volume=19|issue=11|pages=3399–3409|doi=10.1007/s10856-008-3474-6|pmid=18545943|s2cid=27191387}}</ref> and diseases<ref>{{cite journal |last1=Lundmark|first1=Katarzyna|last2=Westermark|first2=Gunilla T.|last3=Olsén|first3=Arne|last4=Westermark|first4=Per|date=2005-04-26|title=Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=102|issue=17|pages=6098–6102|doi=10.1073/pnas.0501814102|pmc=1087940|pmid=15829582|bibcode=2005PNAS..102.6098L|doi-access=free}}</ref> have been triggered by the degraded products of silk fibroin.