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 REPORTING YEAR 

RESEARCH SYNOPSIS

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 in Fall 2015. ERC-RMB and NCAT BMEN programs are facilitating transformational education, outreach, informal education, and diversity. 

Year 08 research efforts continue to build on the substantial progress made in Years 03-07 with greater engagement by clinician specialist members of device-specific 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.

Research

Integrated Systems:

Craniofacial and Orthopedic Applications – Orthopedic device projects continue to mature, with interesting healing data generated from the ACL-ring project. The ACL ring project was part of the option to license held by InCube Labs, Inc.  As part of the option to license renewal (Fall 2015), the ACL ring technology was removed and Naton Medical Group expressed interest.  Dr. Katie Fararro (former ERC PhD. student) spent several months in China with Naton’s Institute of Medical Technology (NMTI) conducting animal experiments and investigating design changes to explore possible device commercialization.  It is anticipated that Naton will support the establishment of a start-up company from their US headquarters in Santa Clara, CA.

Cardiovascular and Thoracic Devices – The AV-Fistula Stent project continues to move forward, exploring novel stent designs and the use of drug-eluting/non-thrombogenic elastomer coatings. Preliminary data suggests reduced neointimal hyperplasia versus uncoated stents. Both R21 and R01 proposals are underway for this project and a start-up company Innovasc has been established to explore the commercial potential of ERC technologies surrounding this project.

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.  In Year 08, the Sfeir and Heineman research groups performed a proof-of-concept study to measure hydrogen concentrations in bone marrow, intramuscular and subcutaneous tissue surrounding a degrading magnesium plate and screw set. This is the first known report of measuring hydrogen gas around a functional magnesium implant. This study demonstrated that there were high concentrations of hydrogen gas in the bone marrow space, but significantly lower concentrations in the intramuscular and subcutaneous space.

Emerging Regulatory Science Focus (ASTM/ISO) – Participation with ATSM work group continues to establish new international standards for safety testing of novel degradable metal implants. Several standards have advanced to the stage of ASTM/ISO committee review. 

Fundamental Science:

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 (including expandable 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

Education and Workforce Development

University Education:

  • NCAT history-making enrollment/graduation of BS (with ABET accreditation visit completed in Fall 2015) and MS students as 1st seamless offering of undergraduate and graduate bioengineering programs at an HBCU.
  • 3 BS, 8 MS and 8 PhD students completed their degrees during the current reporting period.
  • Between 2009 and 2015, RMB’s REU programs have served a total of 48 unique (i.e. non-returning for a second time) participants, plus return summer REUs by 3 of these (total of 51, 4 in Year 08). They have attracted a diverse population in terms of gender, race, and ethnicity, from 12 states and 21 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.

Pre-college Education:

  • Between 2009 and 2015, RMB’s YS programs have served a total of 18 unique participants, plus return summer YSs by 3 of these (total of 21, 2 in Year 08). They have attracted a diverse population in terms of gender, race, and ethnicity, from 13 total secondary institutions in North Carolina. An emphasis was placed on recruitment from RMB’s principal K-12 outreach partner: Guilford County Schools. The 2 YS participants for 2015 were both girls, one each from Guilford County and the adjoining Forsyth County.
  • Between 2009 and 2015, RMB’s RET programs have served a total of 27 unique (never participated before) participants, plus return summer RETs by 13 of these (40 total). They have attracted a diverse population in terms of gender, race, and ethnicity, from 19 total secondary institutions, most in North Carolina and two schools in Illinois. An emphasis was placed on recruitment from RMB’s principal K-12 outreach partner: Guilford County Schools.

General Outreach:

  • # STEM teachers: Visiting / visited by RMB researchers: 45
  • # K-12 students: Visiting / visited by RMB researchers: 977
  • Visitors from industry/legislative/executive/entrepreneur/academia to RMB (~100)

Diversity Advances in the Center:

  • The current (Spring 2016) enrollments are MS: 16 (50 % female, 38 % African-American and 57 % students choosing not to provide race/ethnicity information to the University), and BS: 74 (74 % female, 74 % African-American). Since their inception in Fall 2010, the BMEN degree programs have graduated: MS 13 (46 % female) and BS 9 (67 % 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).
  • 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 4 additional Disclosures, bringing the total to 65, including topics involved in all Engineering Platforms.
  • During the reporting period, ERC-RMB filed 5 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, Dentsply, have led to additional research contracts to support further development of their product opportunity. 
  • Work continues with inCube to characterize and qualify alloys for prototype device development. In vivo evaluations are scheduled to start in late 2016. 
  • In May 2015, a collaborative agreement was signed with Naton Medical Group for the joint development of ACL ring technologies, a document which included provisions for Naton to send a surgeon and engineers to work on product development with ERC-RMB, as well as provide support for research projects and assist with the establishment of a new spin-off company in Santa Clara, CA.

International Partnerships/Collaborations:

  • 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 7th 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 and analysis facility worth $ 2 M was installed with appropriate infrastrural modifications and is almost in the final stages of getting completed with all functionality during the reporting year.
  • Both Pitt and UC commissioned additional materials research infrastructure

B. HIGH-LEVEL RESPONSE AND STATUS TO SWOT FINDINGS OF YEAR 07

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 08, 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 ongoing requests.
  • engaged with the Global Community through ASTM-ISO (Committee AC-87) to develop biodegradable metals testing standards 
  • progressed further in establishing a more focused 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 with more focus abd credibility.
  • For the reporting period, 33 journal papers, 1 trade journal and 22 peer-reviewed conference proceedings papers were published from ERC-supported projects, and 17 (15 journal articles and 2 book chapters) from the associated projects.
  • ERC members attended/led 49 scientific conferences/workshops and gave 55 seminars/colloquia/invited talks.
  • During the reporting period ERC-RMB filed 4 invention disclosures, have been 5 patent applications. Many of invention disclosures and patents include researchers from the all core partner universities.