Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue regeneration of injured human ACL (anterior cruciate ligament)
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27-SY-1 Regenerative silk ligament: scale up and regulatory strategy of a textile engineered silk implant for tissue
regeneration of injured human ACL (anterior cruciate ligament)
Bernhard Küenburg，Andreas Teuschl
MorphoMed, Austria
In the USA around 370.000 annual ACL ruptures in the predominately young population (age 18-30) following sport injuries cause a lot of pain
and long term troubles for the affected patients. The well established standard procedure of autologous tissue transplantation stabilizes the
knee and allows sport activities after 9-12 months. However, harvest of autologous tissue such as patellar tendon or semitendinosus (the most
frequently used autograft) weakens other body areas and long term data show an increased rate of arthroses (up to 50% after 10 years)
associated with ACL reconstructions.
Based on numerous preclinical data and data from a 12-month sheep study the scale-up as well as regulatory approval process of a novel
textile engineered silk implant as ACL graft have been initiated. It is planned to enter a clinical trial and strive for regulatory approval as a
medical class 3 implant. The sheep data (1) have revealed an approximately 50% degradation of the purified medical silk, which acts as
scaffold for the regrowth of a new endogenous ligament. The formation of oriented collagenous tissue fibers including vascularization proves a
ligament tissue regeneration for the first time.
Scale-up and implementation of a commercial process require a defined set of specifications of commercial silkworm (Bombyx mori) silk, a
biological raw material sourced from the textile industry as well as adequate analytical methods to characterize the depletion of sericin in the
course of the production process.
Based on first full scale samples, the defined biocompatibility program has to be executed, in the EU following the ISO requirements of the
notified bodies, in the USA determined by the FDA. Upon submission of the full technical documentation as well as the biocompati-bility data,
approval of a clinical trial can be achieved in order to demonstrate the clinical efficacy of the silk based ACL graft compared to the gold
standard method in two different randomized groups. As primary endpoint the knee stability will be tested by an apparatus supported
Lachmann test. In this study, besides the clinical benefit the patient safety is an important goal. The results of this study will be used for
achievement of regulatory approval.
References:
1) Teuschl A, Heimel P, Nürnberger S, van Griensven M, Redl H, Nau T. Am. J. Sports Med. 2016;44:1547–57. 2) Teuschl
AH, van Griensven M, Redl H. Tissue Eng. Part C Methods. 2014;20:431–9.
