Download 2015 department of medicine research day

2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Novel flowable microporous hydrogel scaffold accelerates wound
healing and decreases scar formation in full thickness cutaneous wounds
Presenter: Philip Scumpia
Division: Dermatology
☒Faculty ☐Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: Tatiana Segura
Co-Investigators: Dino Di Carlo
Thematic Poster Category: Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Atherosclerosis
Abstract
Introduction: Acute and chronic non-healing wounds present a significant burden on both patients
and the health care system. New biologic graft technologies have been developed that can accelerate
wound healing, but are expensive, difficult to apply, require multiple treatments, and do not diminish
scar formation. To this end, we developed a flowable, easy to apply hydrogel composed of micro-sized
polyethylene glycol hydrogel building blocks that uses the coagulation system (factor XIIIa) to rapidly
anneal (<5 minutes) to themselves and to the surrounding tissue. The microporous annealed particle
(MAP) gel displays interconnected microporosity after scaffold formation and we have demonstrated
that it can accelerate wound healing in a murine splinted excisional wound model to simulate human
wound healing (doi: 10.1038/nmat4294). We hypothesized that the bulk host tissue integration will
also result in diminished scar formation and that visible light based annealing using eosin Y would
result in more rapid and more stable scaffold formation when compared to the factor XIIIa-based
annealing.
Materials and Methods: MAP building blocks are produced via a microfluidic water-in-oil emulsion
approach. The building blocks were composed of MMP-degradable PEG hydrogel. Building blocks
anneal to themselves and to the surrounding tissue via a cytocompatible enzyme-catalyzed surface
annealing process (Factor XIIIa) or light based (eosin Y) cross-linking. We utilized a murine fullthickness skin wound healing model and examined the wounds histologically at 7 and 21 days. Skin
contraction (common in murine healing) was prevented using a sutured rubber splint to better
simulate the human healing response. We compared MAP gel to untreated wounds and non-porous
hydrogel controls to explore the importance of a stable scaffold in diminishing scar formation. In some
cases factor XIIIa-annealed MAP gel were compared to Eosin-Y annealed MAP gel at day 1, 7, and 21
days.
Results and Discussion: The MAP gel demonstrated faster healing with 6 of 7 MAP gel treated
wounds demonstrating complete reepithelialization by day 7, whereas only 1 of 7 non-treated or nonporous treated wounds demonstrated complete reepithelialization. Importantly, at 21 days after
wounding, H&E sections demonstrate decreased scar width (p<0.05), with increased regeneration of
hair follicles (p<0.05) and sebaceous glands (p<0.05) directly overlying the full thickness injury and
MAP gel, which are compatible with regenerative healing and diminished scar formation.
Immunofluorescent staining with Collagen I and Collagen III confirms decreased scar collagen within
MAP treated wounds when compared to untreated wounds. When comparing the factor XIIIaannealed MAP gel to the next-generation Eosin Y-annealed MAP gel, the Eosin Y-based annealing
occurred more rapidly (<30 seconds), and appeared histologically similar at 1 day and 7 days post
wounding.
Conclusions: In addition to the accelerated wound healing, the MAP class of biomaterial increases in
situ skin regeneration and decreases scar formation. Preliminary results with visible light-based
annealing suggest its feasibility, which may accelerate clinical use of MAP gel in skin or other tissue.