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

Hernandez, Karina A; Hooper, Rachel Campbell; Boyko, Tatiana; Golas, Alyssa R; van Harten, Michel; Wu, D Q; Weinstein, Andrew; Chu, C C; Spector, Jason A
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.
PMID: 24916020
ISSN: 1552-4981
CID: 2654502

Fabrication and in vivo microanastomosis of vascularized tissue-engineered constructs

Hooper, Rachel Campbell; Hernandez, Karina A; Boyko, Tatiana; Harper, Alice; Joyce, Jeremiah; Golas, Alyssa R; Spector, Jason A
Tissue engineering endeavors to create replacement tissues and restore function that may be lost through infection, trauma, and cancer. However, wide clinical application of engineered scaffolds has yet to come to fruition due to inadequate vascularization. Here, we fabricate hydrogel constructs using Pluronic((R)) F127 as a sacrificial microfiber, creating microchannels within biocompatible, biodegradable type I collagen matrices. Microchannels were seeded with human umbilical vein endothelial cells (HUVEC) or HUVEC and human aortic smooth muscle cells (HASMC) in co-culture, generating constructs with an internal endothelialized microchannel. Histological analysis demonstrated HASMC/HUVEC-seeded constructs with a confluent lining after 7 days with preservation and further maturation of the lining after 14 days. Immunohistochemical staining demonstrated von Willebrand factor and CD31(+) endothelial cells along the luminal surface (neointima) and alpha-smooth muscle actin expressing smooth muscle cells in the subendothelial plane (neomedia). Additionally, the deposition of extracellular matrix (ECM) components, heparan sulfate and basal lamina collagen IV were detected after 14 days of culture. HUVEC-only- and HASMC/HUVEC-seeded microchannel-containing constructs were microsurgically anastomosed to rat femoral artery and vein and perfused, in vivo. Both HUVEC only and HUVEC/HAMSC-seeded constructs withstood physiologic perfusion pressures while their channels maintained their internal infrastructure. In conclusion, we have synthesized and performed microvascular anastomosis of tissue-engineered hydrogel constructs. This represents a significant advancement toward the generation of vascularized tissues and brings us closer to the fabrication of more complex tissues and solid organs for clinical application.
PMCID:4195524
PMID: 24712390
ISSN: 1937-335x
CID: 2654532

Prophylactic Plastic Surgery Closure of Neurosurgical Scalp Incisions Reduces Wound Complications in Previously-Operated Patients Treated with Radiation and Bevacizumab (Avastin) [Meeting Abstract]

Golas, Alyssa R; Boyko, Tatiana V; Schwartz, Theodore H; Stieg, Philip E; Boockvar, John A; Spector, Jason A
ISI:000342420900132
ISSN: 1879-1190
CID: 2654792

Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with bevacizumab (Avastin(R)) and radiation

Golas, Alyssa Reiffel; Boyko, Tatiana; Schwartz, Theodore H; Stieg, Philip E; Boockvar, John A; Spector, Jason A
Neurosurgical craniotomy, craniectomy, or other trans-galeal interventions are performed for a variety of indications, including the resection of benign or malignant tumors, hematoma evacuation, and for the management of intractable seizure disorders. Despite an overall low complication rate of intervention, wound healing complications such as dehiscence, surgical site infection, and cerebrospinal fluid leak are not uncommon. A retrospective review was performed of all patients who underwent scalp incision closure at a single institution by a single plastic surgeon between 2006 and 2013. Sixty patients (83 procedures) were included in the study. Fifty-seven patients (95.0 %) underwent previous craniotomy, craniectomy, or other trans-galeal procedure. Of the total 60 patients, 35 patients received preoperative radiation. Sixteen patients received bevacizumab prior to their index case, while 12 received bevacizumab postoperatively. Ten patients (16.7 %) required additional plastic surgical intervention for wound complications after their index plastic surgery procedure. Plastic surgery was consulted prophylactically in 34 patients (38 procedures). When plastic surgery was consulted prophylactically, 4 patients (11.8 %) required further wound revision. None of the 14 patients who underwent prophylactic plastic surgery closure for previous scalp incision, preoperative bevacizumab, and XRT administration required re-intervention. Plastic surgery closure of complex scalp incisions reduces the incidence of wound complications among patients who underwent previous neurosurgical intervention, XRT administration, and preoperative bevacizumab administration. This is particularly true when plastic surgery closure is performed "prophylactically." Further collaboration between the neurosurgical and plastic surgery teams is therefore warranted, particularly in the setting of these high-risk cases.
PMID: 24872117
ISSN: 1573-7373
CID: 2654512

Reply to "Management of infected groin wounds after vascular surgery" [Letter]

Golas, Alyssa R; Spector, Jason A
PMID: 24819181
ISSN: 1557-8674
CID: 2654522

Tissue engineering for plastic surgeons: a primer

Golas, Alyssa Reiffel; Hernandez, Karina A; Spector, Jason A
A central tenet of reconstructive surgery is the principle of "replacing like with like." However, due to limitations in the availability of autologous tissue or because of the complications that may ensue from harvesting it, autologous reconstruction may be impractical to perform or too costly in terms of patient donor-site morbidity. The field of tissue engineering has long held promise to alleviate these shortcomings. Scaffolds are the structural building blocks of tissue-engineered constructs, akin to the extracellular matrix within native tissues. Commonly used scaffolds include allogenic or xenogenic decellularized tissue, synthetic or naturally derived hydrogels, and synthetic biodegradable nonhydrogel polymeric scaffolds. Embryonic, induced pluripotent, and mesenchymal stem cells also hold immense potential for regenerative purposes. Chemical signals including growth factors and cytokines may be harnessed to augment wound healing and tissue regeneration. Tissue engineering is already clinically prevalent in the fields of breast augmentation and reconstruction, skin substitutes, wound healing, auricular reconstruction, and bone, cartilage, and nerve grafting. Future directions for tissue engineering in plastic surgery include the development of prevascularized constructs and rationally designed scaffolds, the use of stem cells to regenerate organs and tissues, and gene therapy.
PMID: 24378377
ISSN: 1432-5241
CID: 2654542

Vascular smooth muscle cell optimization of vasculogenesis within naturally derived, biodegradable, hybrid hydrogel scaffolds

Golas, Alyssa Reiffel; Perez, Justin L; Fullerton, Natalia; Lekic, Nikola; Hooper, Rachel Campbell; Spector, Jason A
BACKGROUND: As vascularization represents the rate-limiting step in permanent incorporation of hydrogel-based tissue-regeneration templates, the authors sought to identify the material chemistry that would optimize endothelial cell adhesion and invasion into custom hydrogel constructs. The authors further investigated induction of endothelial tubule formation by growth factor supplementation and paracrine stimulation. METHODS: Hydrogel scaffolds consisting of combinations of alginate, collagen type I, and chitosan were seeded with human umbilical vein endothelial cells and maintained under standard conditions for 14 days. Cell density and invasion were then evaluated. Tubule formation was evaluated following basic fibroblast growth factor addition or co-culture with human aortic smooth muscle cells. RESULTS: Human umbilical vein endothelial cells demonstrated greatest cell-surface density and invasion volumes with alginate and collagen (10:1 weight/weight) scaffolds (p < 0.05). Supplementation with basic fibroblast growth factor increased surface density but neither invasion nor tubule formation. A significant increase in tubule content/organization was observed with increasing human aortic smooth muscle cell-to-human umbilical vein endothelial cell ratio co-culture. CONCLUSIONS: Alginate and collagen 10:1 scaffolds allow for maximal cellularization compared with other combinations studied. Growth factor supplementation did not affect human umbilical vein endothelial cell invasion or morphology. Paracrine signaling by means of co-culture with human umbilical vein endothelial cells stimulated endothelial tubule formation and vascular protonetwork organization. These findings serve to guide future endeavors toward fabrication of prevascularized tissue constructs.
PMCID:3843154
PMID: 24281642
ISSN: 1529-4242
CID: 2654552

A prospective analysis of the association between indwelling surgical drains and surgical site infection in plastic surgery

Reiffel, Alyssa J; Pharmer, Lindsay A; Weinstein, Andrew L; Spector, Jason A
INTRODUCTION: Many surgeons fear that closed-suction drains serve as a portal for bacterial entry into surgical spaces. Despite a lack of supporting evidence, postoperative antibiotics are often prolonged while drains remain in place. METHODS: Medical records of all patients who underwent intraoperative Jackson-Pratt drain placement and sterile removal over a 12-month period were prospectively analyzed. RESULTS: Fifty-four patients with 101 drains were included. Drains were in place for 5 to 43 days [mean (SD), 13.5 (6.3) days]. Sixty-three percent of drains had positive cultures. All patients received perioperative antibiotics. Thirty-nine patients received postoperative antibiotics [mean (SD), 13.8 (13.8) days]. There were 2 cases of cellulitis. One patient required reoperation. CONCLUSIONS: Sixty-six drains (65.3%) were placed in the presence of prosthetic material. Although nearly two thirds of drains were colonized with bacteria, our wound infection rate was extremely low (5.6%). Thus, closed-suction drains may be left in place for an extended period without increasing the risk of infection, even in the presence of prosthetic material.
PMID: 23187707
ISSN: 0148-7043
CID: 1196192

Fabrication of cellular tissue constructs from autogenous tissue [Meeting Abstract]

Hernandez, Karina A; Reiffel, Alyssa J; Campbell, Rachel; Derrick, Kadria; Pino, Alejandro; Bleeker, Remco; Harper, Alice; Spector, Jason A
ISI:000325577900189
ISSN: 1879-1190
CID: 2654752

Fabrication of perfusable microvessels within tissue engineered constructs [Meeting Abstract]

Campbell, Rachel; Hernandez, Karina A; Boyko, Tatiana; Reiffel, Alyssa J; Garcia, Daniel; Joyce, Jeremiah; Derrick, Kadria; Spector, Jason A
ISI:000325577900299
ISSN: 1879-1190
CID: 2654762