ERIC SCHMIDT

B E T HA N Y M O O R E , A L E X HE U B E CK , A N D Z ACHA R Y D E CK E R CHR I S TO PHE R WI L S O N , B I OVE N TU S 1 2/ 1 2/ 1 4

• The Baby Boomers (~75 million Americans) • The average baby boomer will be 65 by

the year 2020 • Osteoporosis

• 55% of people currently 50 years old have low bone mass or Osteoporosis

• Osteoporosis causes 1.5 million fractures a year

Curry, Linda C., Mildred O. Hogstel, Pamela J. Frable, and Charles Walker. "Bone Health Among Aging Baby Boomers.“ Internet Scientific Publications. N.p.,n.d. Web. 09 Dec. 2014.

• Current bone grafting techniques require donor tissue • New products (INFUSE®, Amplify®) use BMP-2

• Complications with holding BMP-2 together, burst release • In a study of 151 patients who underwent spinal fusions using Infuse, 35 had

complications due to the high dosage use

• Bioventus solution: Hydrogel molds + Calcium Phosphate granules + BMP-2

• Only problem is the homogenous mixing of these components

Shields, Lisa, George Raque, Steven Glassman, Mitchell Campbell, Todd Vitaz, John Harping, and Christopher Shields. "Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion." Adverse Effects Associated With High-Dose Recombinant Human... : Spine. Spine, 1 Mar. 2006. Web. 02 Oct. 2014.

• Primary Concept • Pros:

• Easily packaged • Simple procedure • Most promising design

• Cons: • Small amount of waste • Forces could shear gel

• Pros: • Simple procedure • No gel shearing

• Cons: • No real mixing agent

• Pros: • Simple procedure

• Cons: • Low reproducibility • Rotational forces could sheer gel

n=1 Not Statistically Significant

n=1 Not Statistically Significant

1. Generate device concepts • Completed

2. Evaluate designs through modeling and testing • Computational modelling • 3D printing prototypes • Hydrogel characterization, Mechanical properties, Protein/Granule

uniformity using microscopy, and Preservation of bioactivity

3. Optimize device and procedure • Reproducibility, Low cost, Ease of use • *Incorporate porosity in mold for increased efficacy*

• Computational Modeling (Ansys Fluent) • Hydrogel Characterization • 3D printing prototypes • Fluorescent Microscopy

• 5 μm thick slices taken at several points along length of mold • BMP-2 Stained with fluorescently tagged antibody for viewing

• Comparative image analysis to ensure uniformity (<10% deviation)

• Calcium phosphate granules also quantified and compared between regions (<10% deviation)

• Test for bioactivity preservation of BMP2 in final mold • Test for mechanical uniformity of mold • Optimization

• Simplify procedure • Determine cost effective/biocompatible

materials • Reproducibility

• Repeat experiments for statistical significance, consistency

• *Porosity within the mold*

• Device will be: • Easy to use • Cheap • Disposable/Sterile

• Procedure will be: • Highly repeatable • Few steps

• Final mold will be: • Homogenously mixed so that:

• BMP-2 evenly distributed throughout mold and on granules (<10% deviation)

• Granules uniform throughout mold (<10% deviation)

• Mechanical properties uniform (<10% deviation)

• Preservation of BMP-2 bioactivity within mold (pass/fail)

• *Porosity for blood vessel penetration*

Task Completion Date Progress Research Prior Art October 15th Completed

Create Concepts November 1st Completed

3D Render Concepts December 1st Completed

Characterize Hydrogel February 1st In Progress

Computational Modeling February 15th In Progress

Prototype Concepts February 15th In Progress

Fluorescence Microscopy March 15th Not Completed

Mechanical Testing March 15th Not Completed

Bioactivity Testing March 15th Not Completed

Repeatability April 1st Not Completed

Materials Research April 15th Not Completed

Procedure Optimization April 15th Not Completed

Incorporate Porosity* April 15th Not Completed

• Chris, Eric and the Bioventus team for their advice and resources

• Dr. Xin Brown for her help with the TA AR 2000 Rheometer

• Dr. Phil Allen training us on some of the basics of fluorescent microscopy