The NIH has awarded Synthasome a grant to develop a pre-clinical model of articular cartilage repair. There is a major need to develop new products to address the major clinical need of articular cartilage repair, particularly for the younger patient. However, there are no agreed-upon models that are established, leading to difficulties in assessing and comparing treatments. There is therefore a substantial need to develop an in vivo model for assessing cartilage repair that can be used to support clinical studies, is consistent between users, and is clinically relevant.

Synthasome has assembled a clinical-academic-industry interdisciplinary team to address this issue. The objective is to generate a set of standard methods for cartilage repair, which are shown to be reproducible between research centers, and can generate uniform data that is appropriate for submission to the FDA to support initiation of clinical studies.

Currently 23 successful surgeries by 6 different surgeons have been performed using X-Repair as an assist device for three different applications (rotator cuff tendon, Achilles tendon, quadriceps tendon). Surgeons are reporting excellent clinical outcome in all cases. Rotator cuff surgeries were performed on large or massive tears, or re-torn tendons. Six of these repairs have been assessed by ultrasound which showed no gap formation.

The R01 research grant “Tissue Engineering TMJ Articular Fibrocartilage” was renewed for year 2010.

As reported previously, Dr. John Lane of San Diego performed the first clinical surgery using X-Repair on August 28th, 2009. This arthroscopic repair of a large rotator cuff tendon re-tear (see below paragraph for more details) has reached its 6-month time point. According to Dr. Lane the patient has excellent clinical outcome to date.

This week the journal Tissue Engineering published a Special Issue dedicated to papers presented at a workshop titled ‘Translational Models for Musculoskeletal Tissue Engineering and Regenerative Medicine’, held in December 2008, preceding the TERMIS-NA meeting in San Diego. Dr Sah (UCSD), Dr Wang (NIH) and I were the co-organizers of the workshop and guest editors of the publication. The objective of the Workshop was to have an open and detailed discussion of the animal models used in this field, their advantages and disadvantages, and highlight particular gaps and needs. The models are a necessary if undesirable component of medical research and product development, and we all wish to ensure the most effective use of these studies. The workshop was a success (attendance was 2.5 times the initial expected attendance), but its lasting impact is the publication of these manuscripts, describing the pros and cons of the field today, and highlighting needs for improvement. An excellent example is the paper presented on models for studying rotator cuff repair, including the model used in the assessment of X-Repair where effectiveness in a challenging and relevant pre-clinical model was a key observation for us to move forward into clinical use of the product.

An important component of the workshop was the presentation by the FDA, now solidified as a manuscript in the Special Issue. Of course the FDA is a critical component of any development pathway for medical products, and more and more they show evidence of reaching out to those involved in research and product development to help ensure that the needs of the agency are met, trying to maximize efficiency of medical product development while ensuring safety of the American pubic. Their continued participation is welcomed!

It is intended that the workshop and subsequent publication serves as a springboard to enhancing the models available, and perhaps move some of these models into more formal standards as developed and published by ASTM. Already there are signs of this occurring with increased activity at ASTM suggesting the efforts made in getting to this stage have been worthwhile. It remains to be seen if these early signs of success are converted to reality, but he indications are positive. The field needs these translational models to effectively assess effectiveness/efficacy and safety of new potential medical products, many addressing unmet clinical needs. It is now in the hands of the researchers to put in place validated models meeting specific clinical problems that can be addressed by tissue engineering and regenerative medicine.

Dr John Lane of San Diego performed the first clinical surgery using X-Repair, used to augment the repair of a rotator cuff tendon. The injury was a re-tear that had been repaired twice previously, and the surgery was performed arthroscopically.

Dr Kathe Derwin, Dr Joe Iannotti and colleagues published an article in the Journal of Bone and Joint Surgery showing X-Repair when used in a pre-clinical study was able to “limit but not eliminate tendon repair retraction, the augmentation device provided a tendon-bone bridge and scaffold for host tissue deposition and ingrowth, resulting in improved biomechanical function of the repair at 12 weeks.” They concluded “the augmentation device, applied in a similar manner as described in the present study, might offer a functional benefit to patients undergoing rotator cuff repair”. [JBJS 91:1159-1191, 2009]