1. Adipose Tissue Engineering: A Therapeutic Strategy for Aging
10 min talk.
5 min Q&A.
Michael Gower
Department of Chemical Engineering
Biomedical Engineering Program
University of South Carolina

2. The adipose tissue is a large organ and a substantial depot for senescent cells during aging
Ouchi et al Nature Reviews Immunology
The senescent secretome promotes age-related diseases
Adipose tissue and its senescent cells are an attractive therapeutic target
Stout et al. Physiology vol32 no1 2016

3. Implantable Technologies for Tissue Engineering and Drug Delivery
Objective:
Develop implantable devices engineered to modulate adipose tissue function
Size of a watch battery.
Porous sponge-like devices made up of an interconnecting network of polymer.

4. Hypothesis: Implants can promote secretory activity that improves metabolism and “healthspan”

5. Scaffolds for adipose tissue engineering
Made of poly(lactide-co-glycolide) (PLG)
Biodegradable Copolymer
Hydrolysis of ester linkages
FDA approved material
Screws
Sutures
Scaffold are designed to release drugs, gene therapy vectors, and cells.
Size of a watch battery.
Porous sponge-like devices made up of an interconnecting network of polymer.

6. Scaffolds Integrate with the Adipose Tissue
Gonadal adipose 28 days after implant
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.
Yellow arrows indicate polymer matrix in contact with adipocytes

7. Scaffolds decrease fat pad weight and adipocyte size
Size of a watch battery.
Porous sponge-like devices made up of an interconnecting network of polymer.

8. Adipocyte size affects secretory activity
Insulin production
Insulin sensitivity
Glucose Uptake
Pancreas dysfunction
Insulin resistance
Hyperglycemia
Size of a watch battery.
Porous sponge-like devices made up of an interconnecting network of polymer.
Fuster JJ Circulation Research, 118(11), 1786–1807.

9. Scaffold implant increases IGF-1 production at the implant site

10. IGF-1 promotes glucose uptake and insulin production
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.

11. Mice with scaffolds have lower fasting blood glucose
IGF-1
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.

12. Mouse model of diet induced prediabetes
Mouse Strain: C57BL/6J
High Fat Diet: Research Diets 60% Fat Diet (D12492)
25g mouse gains ~3-5g in 2 weeks.
This is like a 150 pound human gaining pounds
Prediabetes occurs at 3 days and becomes progressively worse over 3 weeks

13. Increased fat mass and glucose intolerance following 7 days of high fat diet (HFD)

14. Can scaffolds protect mice from HFD?
A scaffold is implanted into both gonadal fat pads (i.e., 2 scaffolds per mouse)

15. Scaffolds protect mice from fat gain during HFD.
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.

16. Scaffolds improve glucose tolerance.
Week 1
Week 2
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.
Week 3

17. What does gene expression look like in skeletal muscle—a major glucose uptake site?
IGF-1?
The scaffold integrates with the adipose after implant.
H&E indicates we have cellular infiltration and and matrix deposition within the polymer scaffold
Arrows indicate Irregular shape structures, which are pieces of polymer near or in contact with adipose.
Note there are many more pieces of polymer than arrows.
(relative to sex, age-matched chow fed mice)

18. Acknowledgments The Gower Laboratory Funding and Resources
Prakasam Annamalai, PhD
Keisha Bonhomme, MD
Michael Hendley, BS
Kendall Murphy, BS
Chris Isley, BS
Heather Struckman
Skyler Marker
Kristina Pond
Milaan Shah
Funding and Resources
COBRE CDSI NIH/NIGMS 1P20GM103641
Start-up package from the University of South Carolina
USC School of Medicine’s Instrument Resource Facility (P20 GM103641)
USC’s Center for Colon Cancer Research (P30 GM103336) for animal space
Exercise Science for use of DEXA
SPARC to Mike Hendley
Magellan to Heather Struckman
Mini-Magellans to Kristina Pond and Milaan Shah

19. Goals for Retreat
Learn about age-related research being done at MUSC and surrounding institutions
Learn about the cellular and molecular mechanisms that govern senescence
Investigate collaborative opportunities with those studying these mechanisms
Learn about animal models of age-related diseases in use at MUSC and surrounding institutions
Long-Term Research Goals
Investigate how biomaterial implant modulates cellular senescence, especially within the adipose tissue
Work towards developing biomaterial-based therapies for age-related diseases
Research Need
Characterization of global gene expression changes within the biomaterial implant site