Kyle J. Miller

Biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune-competent murine model

UNLABELLED Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30-90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA(+) myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. STATEMENT OF SIGNIFICANCE In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the remodeling phase of repair.

Treatment of Spontaneous Osteonecrosis of the Tarsal Navicular With a Free Medial Femoral Condyle Vascularized Bone Graft A New Approach to Managing a Difficult Problem

Adult-onset spontaneous osteonecrosis of the tarsal navicular joint, or Mueller–Weiss syndrome (MWS), is an uncommon debilitating disease characterized by a painful clinical course with progressive midfoot deformity. Treatment options include nonoperative management and/or operative intervention, including percutaneous decompression of the navicular bone, stabilization of existing structures, and cancellous bone grafting from the tibia or iliac crest. To our knowledge, there have been no reported cases of treatment of MWS with a vascularized bone graft. We report an unusual case of unilateral MWS in a 25-year-old male who failed nonoperative therapy and was successfully treated with a novel operative approach using debridement followed by a free medial femoral condyle vascularized bone graft. At 18-month follow-up, the patient demonstrated an excellent outcome with return to previous level of function, including work-related and recreational activities. Level of Evidence: Therapeutic, Level IV: Case study

Major hand replantation after an extended search for the missing part

S ince the first reported hand replantation in 1964, the success of distal extremity replantation has improved secondary to refined surgical techniques and dedicated replantation centers. Hand amputation results in severe functional loss and psychological distress. Every effort should be made to replant the upper extremity because outcomes from replantation exceed outcomes from prostheses. We present a patient in whom extreme measures were taken to locate the dominant, amputated hand, resulting in a successful distal-forearm replantation with a functional thumb. Ischemic time of the hand was 2 hr at the bottom of the river and seven hours hypothermic ischemic time packed in ice. This patient was informed about the collection of data and consented to having his case submitted for publication.

The Effect of Microporous Polysaccharide Hemospheres on Wound Healing and Scarring in Wild-Type and db/db Mice

BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. RESULTS: In wild-type mice, topically applied MPH increased epithelial thickness. Levels of &agr;-smooth muscle actin (&agr;-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor &bgr; levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas &agr;-SMA and transforming growth factor &bgr; levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased &agr;-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. CONCLUSIONS: The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.

Abstract 124: Mitigation Of Hypertrophic Scar Contraction And Stiffening Via An Elastomeric Biodegradable Scaffold

1The Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC, 2Department of Biomedical Engineering, Duke University, Durham, NC, 3Korea Institute of Science and Technology Biomaterials Research Center, Republic of Korea, 4Duke University Medical Center, Department of Pathology, Durham, NC, 5Columbia University, Department of Biomedical Engineering, New York, NY

Abstract 166: Electrospun Synthetic Scaffolds

ConClusion: Our findings indicate that the use of CD90selected ASCs may facilitate more rapid regeneration of skeletal defects. Furthermore, NOG knockdown may serve to augment bone differentiation through an increase in BMP signaling. The integration of these two strategies through magnet-assisted transfection may lead to the development of promising, temporospatially controlled treatments for clinical translation. 166 electrospun Synthetic Scaffolds: a Biomimetic approach to Prevent hypertrophic Scar contraction