Human dental pulp stem cells attenuate the inflammatory response in a mouse xenograft model

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Scientific Poster Presentations: 2015 Clinical Congress

CONCLUSIONS: These studies demonstrate qualitative improvement of healing in wounds treated with electrospun soy scaffold. Ongoing work will seek to optimize scaffold application regimens. The creation of bioactive, soy-based scaffolds as wound dressings constitutes a promising new development for skin regeneration strategies. Foreign body response to five common subcutaneous implants Mohamed M Ibrahim, MD, Manuel A Medina, MD, Jennifer E Bond, PhD, Andrew Bergeron, Carlos Quiles, MD, Latif Bashirov, MD, Howard Levinson, MD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Implanted biomaterials are subject to a significant reaction from the host, known as: foreign body response. We compared the FBR to commonly-used biomaterials to differentiate fibrotic response to these materials. METHODS: Female C57BL/6-mice were used. PVA, cotton and silicone-sheets were cut into 8mm-diameter disks. ePTFE and prolene were cut into 2 cm-long tubes. The implants were inserted subcutaneously. On day 14, 30, 60, 90 and 180, implants were retrieved. Cellularity was assessed with DAPI. Collagen: Masson’s trichrome. Mast cells: Toluidine-blue, Macrophages: F4/80 immune-stain. Capsularthickness and foreign-body giant-cells: H&E. RESULTS: DAPI revealed significantly increased cellularity in PVA. Silicone and ePTFE were least cellular. Silicone showed least cellularity at d14 and d90 whereas ePTFE showed least cellularity at days 30, 60, and 180. Masson’s trichrome sections demonstrated no difference in collagen. Toluidine blue showed no differences in mast cells. F4/80 revealed ePTFE had significantly decreased number of macrophages. On day 14, PVA had highest number of macrophages, whereas prolene had highest number at all time points after day 14. Giant cells increased earlier and gradually decreased later. On day 90, PVA exhibited a significantly increased number of giant cells compared to prolene and silicone. Silicone consistently formed thinnest capsule throughout all time points. On day 14, cotton had formed thickest capsule. On day 30 prolene has formed thickest capsule and on days 60, 90 and 180, PVA had formed thickest capsule CONCLUSIONS: The data reveal differences in capsule-thickness and cellular response in an implant-related manor, indicating fibrotic reactions to biomaterials are implant specific and should be carefully considered when performing fibrosis studies. High-dose and low-dose brachytherapy may be performed safely with soft tissue coverage in salvage treatment of recurrent head and neck cancer Peter W Henderson, MD, MBA, Bhupesh W Parasahar, MD, David M Otterburn, MD, David I Kutler, MD, FACS, Marc A Cohen, MD, Jason A Spector, MD, FACS Weill Cornell Medical College, New York, NY

J Am Coll Surg

INTRODUCTION: Brachytherapy for the treatment of recurrent head and neck cancer (H&NC) can be delivered in 2 forms: highdose radiation (HDR) via removable catheters, and low-dose radiation (LDR) via permanently implanted seeds. Flap coverage of defects after neck dissection is an important surgical adjunct in these salvage procedures, but it is unclear whether the localized delivery of radiation increases morbidity of the transferred tissue. METHODS: A retrospective chart review evaluated patients with recurrent H&NC who underwent flap coverage of surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap or recipient site complications. RESULTS: Nineteen patients were included in the series; 6 received HDR, and 13 received LDR. The mean radiation dose was 21.0  2.4 Gy in HDR, and 81.7  5.5 Gy in LDR. Follow-up was 7.8  6.5 months. Flap viability was 100%, and though there was partial STSG breakdown in 3 subjects, the rate of skin graft take was ultimately 100%. Recipient site complication rate was 31.7%, the HDR group complication rate was 50%, and the LDR group complication rate was 23.1%. There was no statistically significant difference between these 2 groups (p>0.05). CONCLUSIONS: In patients who had flap reconstruction and immediate postoperative radiotherapy following salvage procedures for recurrent H&NC, neither HDR nor LDR impacted long term flap viability or skin graft survival. Flap coverage of defects (with or without skin grafting) in combination with brachytherapy is a safe and effective means of providing soft tissue coverage in these challenging patients. Human dental pulp stem cells attenuate the inflammatory response in a mouse xenograft model Kameron Rezzadeh, Luis A Segovia, MD, Akishige Hokugo, DDS, PhD, Zheyu Zhang, Situo Zhou, Reza Jarrahy, MD David Geffen School of Medicine at UCLA, Los Angeles, CA INTRODUCTION: Inflammatory cytokines have been implicated as key regulators of the wound healing process. Despite this, therapeutic strategies for wound healing geared towards modulating the immune response are lacking. Dental pulp is an efficient and easily accessible source of stem cells for use in regenerative medicine. In this study, we assess the immunomodulatory properties of human DPSCs in an in vitro mouse splenocyte model. METHODS: DPSCs were isolated from human dental pulp and expanded as previously described. Similarly, fully differentiated human fibroblasts and osteoblasts were cultured to serve as controls. A serum containing large quantities of mouse splenocytes was added to each of the human cell cultures. Half of all cell samples were exposed to Concavanalin A, a potent splenocyte activator. The cells were then incubated for seven days. Supernatants were collected and tested for the presence of the inflammatory cytokine IL-6 using ELISA. Samples were also photographed to assess changes in cell morphology.

Vol. 221, No. 4S2, October 2015

RESULTS: The presence of IL-6 was detected in all cell cultures exposed to Concavanalin A, while this cytokine was absent from control culture supernatant. The secretion of this inflammatory cytokine was significantly reduced in co-culutres of splenocytes and human dental pulp stem cells compared to controls. CONCLUSIONS: The physiologic immune response of murine splenocytes is mitigated by the presence of human DPSCs. This may suggest a potential clinical role for DPSCs in wound immunomodulation. In vivo examination of the immunomodulatory properties of DPSCs in a wound healing model is warranted and currently underway. Injectable shape-memorizing 3D hyaluronic acid cryogels (3D-HA) for skin sculpting Liying Cheng, MD, Kai Ji, MD, Anthony Haddad, MD, Ting-Yu Shih, Giorgio Giatsidis, MD, David J Mooney, PhD, Dennis P Orgill, MD, PhD, FACS, Christoph S Nabzdyk, MD Brigham and Women’s Hospital, Harvard Medical School, Wyss Institute at Harvard University, Boston, MA INTRODUCTION: Hyaluronic acid based (HA) fillers are used for various cosmetic procedures. However, due to filler migration and degradation, reinjection of the fillers is often required. Cryogelated methacrylated HA (MA-HA) can be made into injectable, shapememorizing fillers (3D-HA) aimed to address these issues. This study evaluated shape retention, firmness and biocompatibility of subcutaneously injected 3D-HA fillers in mice. METHODS: Fifteen mice each receiving two subcutaneous injections in their back were divided into 4 groups of 4-11 mice each receiving: HA, MA-HA, 3D-HA fillers or saline. Shape retention was confirmed using digital imaging of the skin injection sites. Skin firmness was measured using durometry. In vivo fluorescence imaging was used to track migration and degradation of subcutaneously injected Cy7 containing, saline or HA, MA-HA and 3D-HA fillers. After 30 days, injection sites were harvested and standard histology (H&E), angiogenesis (anti-CD31) and immune cell infiltration (anti-CD45) were evaluated. RESULTS: Digital and in vivo fluorescence imaging revealed that 3D-HA fillers largely maintained pre-determined shape for 30 days. Little to no volume of the fillers or saline was observed in the control groups. There were no differences in skin firmness between the groups or over time. Histology showed intact skin architecture in all groups. 3D-HA maintained its macroporous structure with significant angiogenesis at the 3D-HA/skin interfaces and throughout the 3D-HA filler. There was no significant inflammatory response to any of the injected materials. CONCLUSIONS: Injectable shape memorizing 3D-HA might be a durable, well-tolerated compound for various skin sculpting purposes.

Scientific Poster Presentations: 2015 Clinical Congress

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Intraoral microvascular anastomosis: avoiding visible scars on the face during free tissue transfer Michael Sosin, MD, Mark W Stalder, MD, Amir H Dorafshar, MBChB, FACS, Hugo St. Hilaire, MD, DDS, Eduardo D Rodriguez, MD, DDS New York University Langone Medical Center, New York, NY; Louisiana State University Health Sciences Center, New Orleans, LA; Johns Hopkins Hospital, Baltimore, MD INTRODUCTION: Successful microsurgical free tissue transfer of head and neck defects offer patients unique functional reconstructive solutions. However, patient are left with unsightly facial scars following microsurgical reconstruction. Intraoral microvascular anastomosis is a new technique that precludes the need for a skin incision and may be applied in specific patients to optimize aesthetic outcomes. The purpose of this study is describe our clinical experience using this technique and provide an instructional approach in a cadaveric simulation. METHODS: We present the indications and outcomes of our series of patients who underwent free tissue transfer for reconstruction of major facial defects using an intraoral microvascular anastomosis. Also, a cadaveric dissection was undertaken to demonstrate the accessibility of the facial artery and vein through an intraoral approach. RESULTS: Three patients were identified (2 female, 1 male). Defect etiology varied including palatal defect with oronasal fistula secondary to resection of mucoepidermoid carcinoma, a maxillary defect secondary to resection of fibrous dysplasia, and avascular necrosis of the anterior maxilla secondary to traumatic blast injury. All cases utilized the facial artery and vein as recipient vessels for microanastomosis. Defects were reconstructed with a free ulnar forearm flap, deep circumflex iliac artery flap, and free fibula flap, respectively. All free tissue transfers were technically and achieved a satisfactory aesthetic outcome without any visible scars. The cadaveric intraoral dissection demonstrated a predictable and successful identification of the relevant neurovascular anatomy. CONCLUSIONS: This small series effectively demonstrates the indications, safety, and efficacy of microvascular reconstruction using an intraoral approach to improve aesthetic outcomes. Mitigation of hypertrophic scar contraction in an immunecompetent mouse model via a biostable electrospun scaffold Mohamed M Ibrahim, MD, Kyle J Miller, Latif Bashirov, MD, Ellen Hammett, Youngmee Jung, PhD, Manuel A Medina, MD, Ali Rastegarpou, MD, Angelica M Selim, MD, Kam W Leong, PhD, Howard Levinson, MD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Hypertrophic-scar (HSc) contraction is a debilitating condition that results in disfigurement and decreased range of motion. Current standard of care involves skin-grafting  collagen based, biodegradable, bioengineered-skin-equivalent