Tatiana Boyko

Reduction of suture associated inflammation after 28 days using novel biocompatible pseudoprotein poly(ester amide) biomaterials

Sutures elicit an inflammatory response, which may impede the healing process and result in wound complications. We recently reported a novel family of biocompatible, biodegradable polymers, amino acid-based poly(ester amide)s (AA-PEA), which we have shown to significantly attenuate the foreign body inflammatory response in vitro. Two types of AA-PEA (Phe-PEA and Arg-Phe-PEA) were used to coat silk or plain-gut sutures, which were implanted in the gluteus muscle of C57BL/6 mice, while the uncoated control sutures were implanted in the contralateral side. After 3, 7, 14, and 28 days the mean area of inflammation surrounding the sutures was compared. Phe-PEA coating of silk sutures significantly decreased inflammation compared with noncoated controls (67.8 ± 17.4% after 3d [p = 0.0014], 51.6 ± 7.2% after 7d [p < 0.001], and 37.3 ± 8.3% after 28d [p = 0.0001]) when assessed via analysis of photomicrographs using digital image software. Phe-PEA coated plain-gut sutures were similarly assessed and demonstrated a significant decrease in the mean area of inflammation across all time points (54.1 ± 8.3% after 3 d, 41.4 ± 3.9% after 7 d, 71.5 ± 8.1% after 14 d, 78.4 ± 8.5%, and after 28 d [all p < 0.0001]). Arg-Phe-PEA coated silk demonstrated significantly less inflammation compared to noncoated controls (61.3 ± 9.4% after 3 d, 44.7 ± 4.7% after 7 d, 19.6 ± 8%, and 38.3 ± 6.8% after 28 d [all p < 0.0001]), as did coated plain-gut (37.4 ± 8.3% after 3 d [p = 0.0004], 55.0 ± 7.8% after 7 d [p < 0.0001], 46.0 ± 4.6% after 14 d [p < 0.0001], and 59.0 ± 7.9% after 28 d [p < 0.0001]). Both Phe-PEA and Arg-Phe-PEA coatings significantly decrease the inflammatory response to sutures in vivo for up to 28 days.

Perioperative Antibiotics in the Setting of Oropharyngeal Reconstruction: Less Is More.

BackgroundRecipient-site infection after oropharyngeal reconstruction is a potentially disastrous complication. Although studies suggest that perioperative antibiotics reduces infection rates in these patients from 87% to 20%, there is no consensus regarding what constitutes the most appropriate antibiotic regimen and duration of treatment. MethodsA retrospective review of perioperative antibiotic administration was performed of all patients who underwent local, pedicled, or free flap oropharyngeal reconstruction after oncologic resection by a single surgeon at a single institution between 2007 and 2013 to assess for recipient-site complications. ResultsNinety-seven patients underwent 100 reconstructions (61 free flap reconstructions, 39 pedicled/local flap reconstructions) and all received a combination of intravenous (IV) antibiotic agents designed to cover oral flora. There were 23 (23%) recipient-site complications, which included cellulitis (9%), mucocutaneous fistula (5%), abscess (5%), and wound dehiscence (4%). Duration of antibiotic prophylaxis, defined as less than 48 hours (short-course) or greater than 48 hours (long-course), was not a significant predictor of recipient-site complication. Significant risk factors for recipient-site complications were clindamycin prophylaxis (P < 0.008), increased duration of surgery (P < 0.047), and advanced age (P < 0.034). Recipient-site complication was found to be a significant predictor of both increased length of hospital stay (P < 0.001) and increased time to the resumption of enteral feeds (P < 0.035). ConclusionsThese data suggest that extended courses of perioperative antibiotics do not confer additional benefits in patients undergoing oropharyngeal reconstruction. We recommend a limited 48-hour course of prophylactic antibiotics with sufficient aerobic and anaerobic coverage to help minimize the incidence of antibiotic-related morbidities.

Laboratory Models for the Study of Normal and Pathologic Wound Healing

Summary: Current knowledge of wound healing is based on studies using various in vitro and in vivo wound models. In vitro models allow for biological examination of specific cell types involved in wound healing. In vivo models generally provide the full spectrum of biological responses required for wound healing, including inflammation and angiogenesis, and provide cell-cell interactions not seen in vitro. In this review, the authors aim to delineate the most relevant wound healing models currently available and to discuss their strengths and limitations in their approximation of the human wound healing processes to aid scientists in choosing the most appropriate wound healing models for designing, testing, and validating their experiments.

Abstract 162: in vivo microanastomosis of microvessel containing tissue-engineered constructs: the final frontier.

PurPose: Although autologous tissue transfer has been established as a reliable approach to the reconstruction of complex defects, there are associated consequences including donor site pain, functional loss, paresthesias, dysthesthia, and scarring. The ability to synthesize vascularized constructs for the management of these complex wounds would represent a quantum leap in the field of tissue engineering. In previous work we synthesized and performed an in vivo microvascular anastomosis of a collagen construct containing an unseeded internal longitudinal microchannel with inlet and outlet. Here we fabricate and microsurgically anastomose collagen constructs containing an internal endothelialized microchannel.

Inhibition of IRE1 results in decreased scar formation

Wound healing is characterized by the production of large amounts of protein necessary to replace lost cellular mass and extracellular matrix. The unfolded protein response (UPR) is an important adaptive cellular response to increased protein synthesis. One of the main components of the UPR is IRE1, an endoplasmic reticulum transmembrane protein with endonuclease activity that produces the activated form of the transcription factor XBP1. Using luciferase reporter mice for Xbp1 splicing, we showed that IRE1 was up‐regulated during excisional wound healing at the time in wound healing consistent with that of the proliferative phase, when the majority of protein synthesis for cellular proliferation and matrix deposition occurs. Furthermore, using a small molecule inhibitor of IRE1 we demonstrated that inhibition of IRE1 led to decreased scar formation in treated mice. Results were recapitulated in a hypertrophic scar mouse model. These data help provide a cellular pathway to target in the treatment of hypertrophic scarring and keloid disorders.

A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells.

Background: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation. Methods: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture–seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated. Results: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture–seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel “neovessel.” In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture–seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively). Conclusion: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.

Abstract P29: Optimization of Functional, Perfusable Vascular Networks within Tissue Engineered Hydrogels

eleCtroPhysiology: SSEP negative peak amplitudes were significantly decreased (p<.05) at POD 14, 28, 37, and 79 when compared to baseline with significant recovery at POD 79. SSEP stimulation thresholds were significantly increased (p<.05) at POD 37 and 79 with significant recovery occurring at POD 79. Abductor pollicis brevis thresholds obtained from Tc-MEP stimulation were significantly increased at POD 37 and 79. CNAPs were first measured at POD 42 and confirmed with stimulation-response curve. Nerve conduction velocity was 40% baseline at POD 90 with significantly increased CNAP stimulation thresholds (p<.05).

LOP33: Microstructured collagen scaffolds facilitate deterministic guidance of cells during wound repair

Methods: Tracheal segments harvested from Brown Norway Rat (BN) were programmed frozen for 30 days. The tracheal epithelial cells were removed by washing with PBS for 4 hours at 40°C. Resultant tracheal scaffold was re-epithelized by luminal seeded with epithelial cells isolated from Lewis rat (LEW). These engineered neo-tracheae were subcutaneously implanted to LEW for 30 days. Fresh tracheae from BN and LEW, cryopreserved tracheae and de-epithelized cryopreserved tracheae from BN were transplanted to LEW as controls.

Abstract 197: NOVEL BIODEGRADABLE POLY ESTER-AMIDE (PEA) POLYMER COATING SIGNIFICANTLY REDUCES SUTURE ASSOCIATED INFLAMMATORY RESPONSE

Introduction: Despite their ubiquitous use, surgical sutures are foreign bodies which induce a local immune reaction within the adjacent tissues. This in ammatory reaction predisposes the patient to infection and leads to complications including the development of suture granulomas, tunneling, spitting and abscess formation. We introduce a novel biocompatible and biodegradable (poly (ester-amide) 8-Phe-4 polymer (PEA)) material with anti-in ammatory properties that can be used to coat sutures. We hypothesized that two widely used sutures, plain-gut and silk, would elicit a reduced in ammatory response after being coated with PEA when compared to non-coated controls.

Reduction of Suture-Associated Inflammation Using the Novel Biocompatible Pseudo-Protein Poly Ester Amide (PEA)

IntroductIon: Despite their routine use, surgical sutures are foreign bodies that induce a local immune reaction within adjacent tissue, the consequences of which include wound breakdown, “spitting,” and abscess formation. We have developed a novel pseudo-protein, Polyester amide (PEA), with the potential to modulate the immune response to implantable medical devices. We hypothesized that PEA-coating would reduce the immune response to typically inflammatory suture materials.