Injection of BA-10 at 50 mg/mL resulted in a 32% reduction of tissue modulus over non-injected control specimens and 48% reduction of tissue modulus compared to commercially available hyaluronic acid (Restylane) 24 hours after injection. This exceeded the target of 25% reduction in tissue modulus (increased compliance).
BA-10 molecules diffused over a 4 mm area, which could be beneficial for treating the entire area of a wound. The molecules integrated with the ECM, molecularly engineering the tissue. This is the first time this approach has been demonstrated in skin.
Hydrating molecules could be delivered to skin through injections (including through small gage microneedles (ref) which has been demonstrated in the lab.
Injection of BA-10 at 50 mg/mL resulted in a 32% reduction of tissue modulus over non-injected control specimens 24 hours after injection. In addition, the BA-10 at 50 mg/mL resulted in a 48% reduction of tissue modulus compared to commercially available hyaluronic acid (Restylane). This exceeded the target of 25% reduction in tissue modulus (increased compliance). In addition, it was demonstrated that BA-10 molecules diffused over a 4 mm area, which could be beneficial for treating the entire area of a wound. The molecules integrated with the ECM, molecularly engineering the tissue. This is the first time this approach has been demonstrated in skin. Because BA-10 can be injected via microneedles to allow for application throughout the wound area, minimally invasive delivery of the molecule over the skin surface is possible. Microneedle application is less painful than standard needle application, which could potentially increase patient compliance. The feasibility of modulating tissue mechanics for the dermis to increase compliance by molecularly engineering the ECM of the tissue was demonstrated. This approach could be used to treat wounds, skin tears, and promote efficient healing, limiting scar formation.
Synthetic biomimetic aggrecan is much cheaper and can be synthesized easily. An injection of natural aggrecan can cost $300 while an injection of BA typically costs $0.06. Two to three cubic centimeters (cc’s) are the typical injection volumes for these types of applications, meaning that an injection of BA-10 at 10 and 50 mg/mL would cost approximately $0.60 and $3.00, respectively, in material.
Novel Use of Biomimetic Proteoglycans to Molecularly Engineer the Extracellular Matrix of Damaged Skin
Jessica Gidzinski, David Pearson, Travis Weiss
Advisor: Dr. Michele Marcolongo
Mentors: Alicia Kriete, Evan Phillips, Dr. Katsiaryna Prudnikova
Novel Use of Biomimetic Proteoglycans to Molecularly
Engineer the Extracellular Matrix of Damaged Skin
Problem: As skin ages, it dehydrates and loses
• Vulnerability to wounds/infection
o 92% of institutionalized elderly sustain
at least 1 skin tear every year
2MALONE, ML, et al. "the Epidemiology of Skin Tears in the Institutionalized Elderly."JOURNAL OF THE AMERICAN GERIATRICS SOCIETY 39.6 (1991): 591-5. Web.
Skin Layers and Molecular Composition
● ECM: offers structural and
○ Structural proteins
○ Proteoglycans (PGs): embed
structural proteins & are critical
for wound healing
■ PG breakdown over time
causes dehydration and
Protein core with covalently attached
glycosaminoglycan (GAG) chains
o Increased water uptake (hydration)→
negatively charged GAG chains
○ PGs aid in last 2 stages of wound healing
1. Cell migration/proliferation (fibroblasts)
2. Remodelling: bind to type I collagen fibers
in skin to align them in organized fashion
Proposed Solution - Biomimetic Proteoglycans (BPGs)
• Increased hydration & compliance
• Restored PG content could potentially
enhance wound healing
o PGs align collagen fibers during
o High PG content→less scarring
Marcolongo, M. "Matrix Molecular Engineering Using Biomimetic Proteoglycans." 26 Oct. 2015. Lecture.
Lightfoot Vidal, Sarah Eugenia, Michele S. Marcolongo and Drexel University. College of Engineering. "Novel Biomimetic Aggrecan for the Acellular Regeneration of the Intervertebral Disc: Synthesis, Enzymatic Stability and
Molecular Engineering." 2013. Web.
Objectives and Methods
Objective 1: Determine if BPGs have a statistically
significant effect on skin compliance
Method: Employ piezoelectric finger (PEF) method to
measure elastic modulus of BPG-injected porcine skin
Objective 2: Evaluate the diffusion behavior of BPGs
Method: Cryosection samples thin enough to view
under confocal microscope; quantify percent area
fluorescence of tagged BPGs at varying distances from
Piezoelectric Finger (PEF) Method
Xu, Xin, Cynthia Gifford-Hollingsworth, Richard Sensenig, Wei-Heng Shih, Wan Shih, and Ari D. Brooks. "Breast Tumor Detection Using Piezoelectric
Fingers: First Clinical Report." Vol. 216, No. 6. Drexel University, June 2013.
Exceeded target of 25%
reduction in modulus
Confocal Microscopy Results
● Decrease in amount
of molecule near
injection sites over
24 hr period
● Overall, molecular
around injection site
is shown over a 24
Overall Conclusions and Design Considerations
• For the first time, demonstrated molecular
engineering of the ECM of porcine skin using
• The skin hydration and increased compliance
caused by injectable BPGs offers potential for
treatment of diseased and aged skin against
tearing and subsequent infection.
o An injection of natural PGs can cost $300/mg
while an injection of BPGs typically costs