- Background: The human body is a complex and unique phenomenon—one that enables physicians to use innovative and exciting medical technologies to help the body heal itself. Regenerative medicine is one of those exciting and emerging areas of healthcare that channels the body’s own transformative capabilities. Physicians from varying specialties are using diverse aspects of regenerative medicine with outstanding results for patients. These techniques include using dermal grafts—transplanting tissue beneath the skin—to using a patient’s own cartilage to help the healing process. For example, at NorthShore Orthopaedic Institute, surgeons are taking healthy cartilage from a patient, growing the cells in the lab and then transplanting the cartilage cells back into the patient’s knee. Cartilage has no ability to heal but regenerative medicine is enabling cartilage to regrow in patients, and in many cases, giving them better outcomes in returning to an active life within months of surgery. In addition, growth factors—naturally occurring proteins in the body—can be used for certain spine surgeries to promote stronger healing and, ultimately, a quicker recovery time for patients. Equally exciting is the work researchers are conducting in the field of bio/nanotechnology to craft synthetic grafts for ACL reconstructions that could have the potential to improve post-surgery results. Regenerative medicine remains an area of constant growth and development but also is showing improved care and positive outcomes for patients.
- Speaker Bios: (in order of appearance)
Guillermo Ameer is Professor of Biomedical Engineering at Northwestern University. He joined the faculty of the Biomedical Engineering Department at Northwestern in 2001 and also was appointed professor in the Department of Surgery at Northwestern’s Feinberg School of Medicine. A native of Panama City, Panama, he received his bachelor degree in Chemical Engineering from the University of Texas at Austin and his doctor of science degree in Chemical and Biomedical Engineering from the Massachusetts Institute of Technology. Dr. Ameer's research interests include biomaterials, vascular and orthopaedic tissue engineering, controlled drug and gene delivery, stem cell engineering and bio/nanotechnology for improved therapeutics and diagnostics. He has co-authored more than 100 peer-reviewed journal publications and conference abstracts, several book chapters, and multiple patents issued and pending. He is co-founder of three companies: ProSorp Biotech, VesselTek Biomedical and Citrics Biomedical. He has served on several scientific review committees for funding research at the state and federal levels and was one of 100 invitees by the National Academy of Engineering to attend the 10th annual Frontiers of Engineering Symposium. Dr. Ameer served as a permanent member of the Musculoskeletal Tissue Engineering study section of the National Institutes of Health. To accomplish his research goals, Dr. Ameer has assembled a team of collaborators that includes Dr. Jason Koh, and Stuart Sprague, MD, Director of the Division of Nephrology and Hypertension at NorthShore University HealthSystem.
Jason Koh, MD, is an internationally known orthopaedic surgeon specializing in sports medicine with a focus on knee, shoulder and elbow reconstruction. Dr. Koh is the Endowed Board of Directors Chair of Orthopaedic Surgery at NorthShore Orthopaedic Institute, part of NorthShore University HealthSystem. He is also a Clinical Associate Professor at University of Chicago Pritzker School of Medicine. After graduating magna cum laude from Harvard University, he attended medical school at the Johns Hopkins University. He then completed a surgical internship at Massachusetts General Hospital and an orthopaedic residency at the Hospital for Special Surgery, Cornell Medical School. His fellowship in sports medicine was at the Cleveland Clinic. Dr. Koh is the recipient of numerous awards, including the American Orthopaedic Association North American Traveling Fellowship, the American Association of Orthopaedic Surgery Leadership Fellowship and the Patellofemoral Foundation Traveling Fellowship. He has served as visiting professor at multiple institutions and has lectured extensively across the world. He has written more than 40 papers and book chapters, and has made over 150 scientific presentations. His research has been recognized by the Richard O’Connor Award from the Arthroscopy Association of North America and the Charles Neer Award from the American Shoulder and Elbow Society. He was previously the Medical Director for the Joffrey Ballet, orthopaedic surgeon for the Chicago Fire Soccer Team and orthopaedic consultant to the Chicago Cubs. Dr. Koh also has served as President of the Northwestern Medical Faculty Senate and is past President of the Illinois Association of Orthopaedic Surgeons. He maintains a busy clinical practice and is an investigator for several ongoing clinical trials. His peers have recognized him as a “Best Doctor” and one of America’s “Top Physicians.”
Daniel Lee, Chief Executive Officer, Aperion Biologics, has more than 20 years experience in the medical device industry. Prior to joining Aperion in 2008, Mr. Lee was responsible for the TRUREPAIR business unit at Smith & Nephew Endoscopy. Prior to Smith & Nephew, he was responsible for global marketing activities at OsteoBiologics Inc. (OBI), which provided the only off-the-shelf bioabsorbable implant for articular cartilage repair in Europe. OBI was acquired by Smith & Nephew in 2006. Prior to joining OBI, Mr. Lee was the Director of Marketing for Regeneration Technologies Inc. (RTI), a leading allograft tissue processor for orthopaedic, spinal, craniofacial and urologic surgical applications that went public in 2000. While at RTI, Mr. Lee played a key role in creating and establishing RTI’s Sports Medicine business unit. Prior to joining RTI, he was the Director of the Sports Medicine Research and Development group at Surgical Dynamics, a subsidiary of U.S. Surgical Corporation. Much of his experience at U.S. Surgical focused on using resorbable materials for orthopaedic products. He is a member of the Society for Biomaterials and the American Association of Tissue Banks where he holds a Certified Tissue Bank Specialist certification. He currently holds eleven patents on implants and instruments used in orthopaedic and general surgery. Mr. Lee earned a Master of Science in Biomedical Engineering from the University of Alabama at Birmingham and a Bachelor of Science degree in Materials Science and Engineering from the Johns Hopkins University.
- Dr. Ameer was going fast and furious. He was talking about using citric acid-laced scaffolds in innovative ways. Here's a quote about the general technique:
"Biodegradable scaffolds play an important role in creating a 3D environment to induce tissue formation. The application of scaffolding materials together with stem cell technologies are believed to hold enormous potential for tissue regeneration" from:
- Citric acid materials polymers. Outcome. Elastic elastomer. Tune its degradability. Porous Elastomeric scaffolds. Tweak mechanical properties. Blend w ceramics other cells. Give it antioxidant properties. The antioxidant material is expected to inhibit lipid peroxidation.
Most devices are plastic, so they produce inflammation. Stents, too, create oxidative stress. Ascorbic acid in scaffolds can scavenge radicals.
Example diabetes. High oxidative stress.
Sdf-1 plays well w stem cells and body's natural process. Can embed natural anti inflammatory materials into scaffold.
Regenerating bone tissue. Replace ligament structure. Osteoporosis not an application. This [regenerative technique] is more for localized wounds.
Vascular disease. Treatment. Grafts. Fail often. Oxidative stress scar tissue. Can coat vascular grafts w polymer. Then seed polymer w patients' own cells. Polymer reduces propensity to clotting. Replace Teflon w more bio material.
Vitamin A. Deliver outside vessels it permeates the walls and heals. Reduces inflammation and scar tissue. Put material on each side of grafts to cut inflammation.
New way to stent. Light based stent arteries. Lab bench data suggests it outperforms metal stents in pigs, and pig studies for the light-based stenting are about to commence. 3D print the polymers stents.
(Thanks Guillermo for the tweaks in some of the finer points!)
- During aging, time trauma take their toll. Active lifestyle is desired. Constant bone and joint pain cause of half of cases with reduced mobility. 27% joint pain usa. Heal by regenerating [the body's] own tissue. Children have high plasticity, we study [their cells'] behavior. Stem cells decrease w age. What increases are fibrosis abd inflamation, what decreases is regeneration. the NIH only gives 1.7% of its budget joint and inflamation [even though it's such a common problem].
Poly citric acid polymer. Lactic acid. Holes [in scaffold] enable body cells to integrate into material. Huge gap BT research and patient care. Synthetic spine replacements. Knee cartilage replace example. Now this treatment is better for "potholes" in knee, not resurfacing yet. The latter currently in clinical trial.
Stem cells to treat spine. #BigData has huge potential. #NorthShoreWeb is on EPIC systems, we're one of the top three in the USA in using Healthcare IT in practice. We use #BigData for predictive modeling. From the bench to the bedside.
Q pro athletes. He treats a lot of athletes. They often go for stem cell treatments, but there's very little research behind them. One case in Europe of growing nose cartilage in the knee due to indiscriminate stem cell treatment, people are throwing stem cells around too easily.
Q plasma cells. Spine stem cell. He does shoulders and knees. Uses treatments w scientific research behind them. Prefer proof with imaging that shows true structural change, not patient-reported results, as are the norm. Stem cells available for therapy are very few in most people. Pro athletes have the treatment covered under worker's compensation policies.
Placenta full of stem cells. Exogenous sources from placenta or animal cells are plentiful and inexpensive [but they can create inflamation]
- Mr. Lee leads Aperion Biologics, which is commercializing a "platform" [scaffold] for regenerative medicine. Here's an overview:
- For example, take animal Tissue grafts. Ist prod out ACL-R replace device. The problem is there is a shortage of donor cells and they are expensive. Animal tissue plentiful but need to strip of antigens. CMI. Enzyme wash humanize tissue. Video.
We took the technology to Europe. This product behaves like human tissu z-lig. ACL market huge. Trial has patient cohort three plus years out with good results. Fundraising to scale manufacturing. In the USA, trial cost prohibitive.
- Entrepreneurial side. Think of Investors, patients, and MDs as customers. Think like this. Build different valuprops for each customer. Investors will have questions about your planned Exit and risks. Also, is it a $1B product or $100M? Porcine cells may not fly in Muslim countries.
Commercialization of regenerative products. Need the right team. Stakeholders need patience, your venture will take time and some luck. Overview of the product development process:
- Natural scaffolds. Animal tissue engineering. Today ortho and cardiovascular applications.
Manufacturing. Biolotical material much harder, cells are not inorganic materials. Process to scale. Reduce steps in mfg. Medical has to be high quality. Pursue global quality standards like ISO.
Finance. You'll need more money than you think need. Fundraising is perpetual. Get smart money [from people who know some aspect of your business cold].
Regulations. Regenerative products are new to the FDA, which doesn't know the field, so this slows process. Part of it is how is your product classified? Is it a Bio device or allograft? How defined? PMA requires a 3 phase trial. Compare your product to an existing product if possible. 510k option. Combination [of two categories] products very hard for FDA, different parts of the FDA confused. OUS (outside US) a good option, "notified bodies." Europe easier, more predictable.
Overview of the gotchas/hurdles of commercialization:
- Marketing. Know your market. Competitors. Customers. Dependencies [of your product, business]. Its ease of use. Does it require clinician training? That's a barrier.
Reimbursement. Will you be paid? How much? Data helps especially if it's more expnsive procedure than the norm.
Distribution. Direct sales force, partners, distributors, shipping? Our products must be shipped frozen, these are bio. Dry ice $1k per box to Europe.
Legal. IP (intellectual property). Patents. Build fences. Broad as possible. People/competitors will copy if you're successful. Freedom to operate good.
Q. Lurie funding one of our key investors.
- QA. Panel. Asia market? We had that debate. Investor wanted USA. Europe is a smaller market but there's no competition there.
Dawn Gay. How do patients find you (to Dr. Koh)? How does Value-based medicine compare? Transparency increasing about outcomes. Websites ofteb based on patient experience. Process. Ernest Codman. Founder JCHO and champion of outcomes medicine. A challenge to match people w trials.
Bundling? Medical world. That's when you pay for complete episode of care. A Medicare pilot has cut costs dramtically. Everyone gets paid for one thing. Parties divide it. Few comparative trials. #BigData can be huge.
ACL in Europe. Scandinavia collects all data on surgery 95%. Also access clinician outcomes. Quality of life scores. Sf36.