2014-2015 Executive Summary
Research efforts within Engineering Research Center for Revolutionizing Metallic Biomaterials (ERC RMB) continue to mature and evolve, emphasizing: 1) synergy of research efforts across ERC RMB institutions and engineered systems (ESs) driven by the research strategic plan; 2) excellence in education; and 3) dynamic outreach activities that highlight the quality and diversity of the ERC RMB.
A. ACHIEVEMENTS IN THE 2014-2015 REPORTING YEAR
ERC-RMB 3-Plane Strategic Framework with Barriers
The strategic research plan emerged in Years 01 and 02 from the 3-plane chart and feedback by science advisors to identify device specific test beds within each engineered system (ES). A device focus emerged that enabled strategic decision-making regarding research projects and science projects to address in vivo performance of degradable alloys as devices. Year 03 through Year 05 efforts were dedicated to the development of science and research thrusts to support device test beds within each ES. Materials development Thrust (Red Team), Materials processing/characterization coatings and modeling Thrust (Blue Team), and Biocompatibility Thrust (Green Team) provided the fundamental knowledge to advance the development of device prototypes/testbeds moving forward.
Advances in ERC-RMB science have been matched by ERC-RMB achievements in education and outreach, which are highlighted by the awarding of the first baccalaureate and master degrees in biomedical engineering by a historically black college and university. In year 07 NCAT BMEN Chairperson, Dr. Stephen Knisley, with his wealth of experience in BMEN education, research and administration, led the BMEN faculty in preparations for the BS programs first ABET accreditation visit, scheduled for Fall 2015. ERC-RMB and NCAT BMEN programs are facilitating transformational education, outreach, informal education, and diversity. Details are given in the appropriate sections of this report.
Year 07 research efforts continue to build on progress made in Years 03-06 with greater engagement by clinician specialist members of device advisory boards and industry collaborators to focus opportunities for translation. In particular, the development, processing and testing of novel degradable alloy systems has emerged as an area of strategic interest among ERC-RMB member companies, including new IAB members. The underlying premise is that ERC-RMB sustainability is intimately tied to the intellectual strength of the team’s basic research, translational opportunities for our technologies and the commercial interest developed around this potential, as well as the educational impacts associated with next generation, diverse workforce quality and development.
Craniofacial and Orthopedic Applications – Orthopedic device projects continue to mature, with interesting healing data generated from the ACL-ring project. Refinement of the device and methodology for insertion continue.
Cardiovascular and Thoracic Devices – The AV-Fistula Stent Project is moving forward, exploring novel stent desgns and the use of drug-eluting/non-thrombogenic elastomer coatings . Preliminary data suggests reduced neointimal hyperplasia vs, uncoated stents.
Enabling Technologies and Cross-cutting Activities:
Novel Material Processing – Methods for extrusion and thermal treatment of novel alloys developed at NCAT were applied ERC wide to enhance alloy properties.
Novel Coating Technology: A controlled passivation technology based on electrochemical etching was developed and tested.
Biocompatibility – Advanced basic research to identify the molecular mechanisms for improved bone and wound healing from Mg-based alloys.
Emerging Regulatory Science Focus (ASTM/ISO) – Participation with ATSM work group was implemented to create new international standards for safety testing of novel degradable metal implants. Several standards have advanced to the stage of ASTM/ISO committee review.
Corrosion Science – Bioreactors modeling dynamic conditions in bone and the vascular space were developed and tested
Materials Science -The materials team developed series of Mg-based novel ERC alloys using strengthening functions of alloying elements, grain refinement ability of alloying elements and understanding the functions of alloying elements in corrosion. Improved heat treatment to prepare single phase Mg-Zn-(Ca)-REs to enhance mechanical and degradation properties as well as extrusion and wire drawing helped to manipulate microstructures resulting in understanding the property- structure relationships for the ERC- RMB Mg system
In vivo studies maturation:
ACL-Ring: A pilot study (N = 7) was performed in skeletally mature, female Spanish goats to investigate the advantages of using an Mg-alloy repair ring with a sheet of extracellular matrix (ECM) and hydrogel for ACL healing. Preliminary results suggest feasibility of the approach as an alternative to ACL replacement.
AV-Fistula Stent: Generation III stents were extensively tested in the pig model. In the experiment, AVFs were created bilateral in the groin AVFS on one side and the control AVF on the contralateral side. Clinical end points of flow and diameter were measured. Mild neointimal hyperplasia (NH) was observed at stented segment. Heavy NH was observed in non-stented fistula. No necrosis was observed. New stent designs (Generation IV) and novel coatings technologies are being studied to reduce NH.
Education and Workforce Development: University Education
- NCAT history-making enrollment/graduation of BS and MS students as 1st seamless offering of undergraduate and graduate bioengineering programs at an HBCU.
- 6 BS, 5 MS and 5 PhD students completed their degrees during the current reporting period.
- Between 2009 and 2014, RMB’s REU programs have served a total of 44 unique participants, plus return summer REUs by 3 of these (total of 47, 5 in Year 07). They have attracted a diverse population in terms of gender, race, and ethnicity, from 11 states and 19 total institutions. An emphasis was placed on recruitment from RMB’s principal outreach partners including California State University – Los Angeles (an HSI) and Guilford Technical Community College (GTCC) in Greensboro.
Education and Workforce Development: Pre-college Education
- Between 2009 and 2014, RMB’s YS programs have served a total of 17 unique participants, plus return summer YSs by 2 of these (total of 19, 4 in Year 07). They have attracted a diverse population in terms of gender, race, and ethnicity, from 10 total secondary institutions in North Carolina. An emphasis was placed on recruitment from RMB’s principal K-12 outreach partner: Guilford County Schools.
- Between 2009 and 2014, RMB’s RET programs have served a total of 25 unique participants, plus return summer RETs by 11 of these (total of 36, 5 in Year 07). They have attracted a diverse population in terms of gender, race, and ethnicity, from 18 total secondary institutions, most in North Carolina and two in Illinois. An emphasis was placed on recruitment from RMB’s principal K-12 outreach partner: Guilford County Schools.
Education and Workforce Development: General Outreach
- # STEM teachers: Visiting / visited by RMB researchers: NCAT (149), UC (26),
- # K-12 students: Visiting / visited by RMB researchers: NCAT (476), UC (1358)
- Visitors from industry/legislative/executive/entrepreneur/academia to RMB (~100)
Education and Workforce Development: Diversity Advances in the Center:
- The current (as of Fall 2014) enrollments are BS: 70 (74 % female, 74 % African-American), and MS: 14 (36 % female, 36 % African-American and 57 % students choosing not to provide race/ethnicity information to the University). Since their inception in Fall 2010, the BMEN degree programs have graduated BS 6 (33 % female) and MS 12 (50 % female). Many students have successfully found employment in industry (Baxter International, St. Joseph’s), graduate and/or professional schools and post-doctoral fellowships (Pitt, Penn State, UC, Univ. of North Carolina – Chapel Hill, Univ. of Utah, Univ. of Virginia, Rutgers).
- ERC-RMB outreach partner CSU-LA (65% Hispanic-serving) is working with NCAT in microfluidic drug delivery research areas – a major research initiative at NCAT RMB. Additionally, the partnership is providing for student exchange through summer programs – 16% of RMB REU participants to date have been Hispanic.
- Continuation of special efforts to promote diversity at Pitt and UC by Drs. Wosu and Pixley
Technology Transfer and Commercialization (Innovation Ecosystem):
- In the present reporting year, the ERC has produced 16 additional Disclosures, bringing the total to 65, including topics involved in all Engineering Platforms.
- During the reporting period, ERC-RMB filed 7 patent applications.
- Revisions to the Membership Agreement implemented at the end of the previous reporting period have resulted in an increased dialog with industry. 2 new members have signed, and several more are in active discussions.
- Interactions with one new member, Dentsply, have led to a product prototype. A research agreement is being drawn up to support further development of this product opportunity.
- SBIR/STTR/SECO grants (ongoing with NanoMag, final report filed with OrthoKinetics Lab)
- Work continues with inCube to characterize and qualify alloys for prototype device development. In vivo evaluations are scheduled to start in the 3rd quarter.
- Dr. Witte, University Professor at Charite, Universitatsmedizin Berlin, continued the ERC global activities through participation in AC-87 Biodegradable Metals Standardization Committee and co-organizing the 6th Biometals Conference in Maratea, Italy.
- Dr. Witte continues to have active research interaction with various ERC technical team members
Center Infrastructure, Including Personnel:
- NCAT College of Engineering has provided BMEN teaching and research laboratory space in Hines Hall (Rooms 217, 218, 219), McNair Hall, and Cherry Hall to the Bioengineering programs. These spaces have been fully utilized for bioengineering curricular and faculty research activities. The Hines Hall facility has been renovated and research/instructional lab infrastructure and equipment are in place.
- An additional research facility for Mg extrusion processing and an additional materials characterization facility worth $ 2 M have been added to the NCAT RMB infrastructure.
- Both Pitt and UC commissioned additional materials research infrastructure
B.HIGH-LEVEL RESPONSE AND STATUS TO SWOT FINDINGS OF YEAR 06
Selected initiatives undertaken to address weaknesses, opportunities and threats include
- revisions to the Industrial Affiliates Membership agreement designed to enhance industrial engagement are fully executed and bearing promising results
- In Year 07, all project proposals were shared for review with the CSAB and IAB Chairs, and as well as with appropriate CSAB and IAB members based on their research/development interest. The critical inputs were shared with the PIs to discuss with the CSAB, IAB members and modify their proposal activities accordingly. Further, the project activities were continuously tweaked based on the participation and involvement of the entire ERC team (including students and post-doctoral scholars) via our joint (ERC+CSAB+IAB) Friday 4:00 PM webinar series.
- ERC-RMB has initiated during this reporting year an infrastructure user fee charging mechanism, which has already proven successful, with multiple requests.
- engaged with the Global Community through ASTM-ISO (Committee AC-87) to develop biodegradable metals testing standards
- progressed in establishing Clinical Advisory Boards specific to device projects
Publications / Patents / Key Meetings
- The impact of ERC RMB’s science continues to be demonstrated through a strong publication record and presence at key symposia, including as invited/keynote speakers. Invention disclosures and patent applications are increasing.
- For the reporting period, 34 journal papers, and 14 peer-reviewed conference proceedings papers were published from ERC-supported projects, and 30 (29 journal articles and 1 peer-reviewed proceedings) from the associated projects.
- ERC members attended/led 29 scientific conferences/workshops and gave 62 seminars/colloquia/invited talks.
- During the reporting period ERC-RMB filed 16 invention disclosures, have been 7 patent applications. Many of invention disclosures and patents include researchers from the all core partner universities.