Ultrasound shear wave elastography effectively predicts integrity of ventral hernia repair using acellular dermal matrix augmented with platelet-rich plasma (PRP).

BACKGROUND: Complications of ventral hernia repair (VHR) may be investigated by computed tomography or ultrasound (US) but neither modality gives a quantifiable metric of repair quality short of identifying hernia recurrence. Platelet-rich plasma (PRP), a growth factor-rich autologous blood product, has been shown to improve incorporation of native tissue with bioprosthetics. In this study, we investigate the effect of PRP on the incorporation and mechanical integrity of a non-crosslinked porcine acellular dermal matrix (pADM) in a rodent model of VHR and the correlative ability of ultrasound shear wave elastography (US-SWE) to assess repair quality. METHODS: PRP was isolated from whole blood of Lewis rats. Twenty-eight Lewis rats underwent chronic VHR using either pADM alone or augmented with autologous PRP prior to non-invasive imaging assessment and specimen harvest at either 3 or 6 months. US-SWE was performed to estimate the Young's modulus prior to histological assessment and data from PRP-treated rodents were compared to controls. RESULTS: Implanted pADM was easily distinguishable by US-SWE imaging in all cases analyzed in this study. The mean Young's modulus measured was 1.78 times and 2.54 times higher in PRP-treated samples versus control at 3-month and 6-month time points respectively (p < 0.05). At 3 months, qualitative and quantitative histology revealed decreased inflammation and improved incorporation in PRP-treated samples along the implant/abdominal wall interface. At 6 months, the PRP cohort had no hernia recurrence and preserved ADM integrity from immunologic degradation, while all control animals suffered hernia recurrence (4/6) or extreme ADM thinning (2/6). CONCLUSION: This study confirms both the efficacy of PRP in augmenting VHR using pADM, as well as the reliability of US-SWE to non-invasively predict the quality of VHR. Although further human studies are necessary, this work supports PRP use to improve VHR outcomes and US-SWE potential for bedside non-invasive hernia characterization.

Characterization of ventral incisional hernia and repair using shear wave elastography.

BACKGROUND: To assess the integrity of hernia repair, imaging modalities such as computed tomography or ultrasound (US) are commonly used. Neither modality has currently the capacity to simultaneously image the mesh and quantify a prosthetic and surrounding tissue stiffness. In this pilot study, we hypothesize that US shear wave elastography (SWE) can be used to identify a polyester mesh and a biologic graft and to assess their stiffness noninvasively in a rat model of bridging hernia repair. METHODS: Lewis rats underwent hernia creation and repair with Parietex or Strattice at 30 d. After 3 mo, the animals were euthanized, and the Young's Modulus was measured using SWE. Three-dimensional reconstructions of the hernia pre- and post-repair were performed using in-house image processing algorithms. RESULTS: SWE was capable of accurate and real-time assessment and diagnosis of the hernia defects in vivo. Young's Modulus of Parietex meshes and Strattice grafts as estimated from the shear wave elastograms were found to be statistically different from each other (P < 0.05). Accurate three-dimensional reconstructions of the hernia defects pre- and post-repair were generated. CONCLUSIONS: In this study, we demonstrate the feasibility of using US SWE to detect ventral hernias and evaluate mesh repair in vivo. Our results indicate that the presence of a hernia and repair can be reliably visualized by SWE and three dimensionally reconstructed. Thus, this technique may provide both structural and functional information regarding the hernia and the repair.

Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing.

Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications.

Cross-linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet-rich plasma in a rat model of hernia repair.

The degree of cross-linking within acellular dermal matrices (ADM) seems to correlate to neovascularization when used in ventral hernia repair (VHR). Platelet-rich plasma (PRP) enhances wound healing through several mechanisms including neovascularization, but research regarding its effect on soft tissue healing in VHR is lacking. We sought to study the effect of cross-linking on PRP-induced neovascularization in a rodent model of bridging VHR. We hypothesized that ADM cross-linking would negatively affect PRP-induced neovessel formation. PRP was extracted and characterized from pooled whole blood. Porcine cross-linked (cADM) and non-cross-linked ADMs (ncADM) were implanted in a rat model of chronic VHR after treatment with saline (control) or PRP. Neovascularization of samples at 2, 4, and 6 weeks was assessed by hematoxylin and eosin and immunohistochemical staining of CD 31. Adhesion severity at necropsy was compared using a previously validated scale. Addition of PRP increased neovascularization in both cADM and ncADM at 2- and 4-week time points but appeared to do so in a dependent fashion, with significantly greater neovascularization in the PRP-treated ncADMs compared to cADMs. Omental adhesions were increased in all PRP-treated groups. Results indicate that, for 2-week measurements when compared with the cADM group without PRP therapy, the mean change in neovascularization due to ncADM was 3.27 (Z = 2.75, p = 0.006), PRP was 17.56 (Z = 14.77, p < 0.001), and the combined effect of ncADM and PRP was 9.41 (Z = 5.6, p < 0.001). The 4-week data indicate that the average neovascularization change due to ncADM was 0.676 (Z = 0.7, p = 0.484), PRP was 7.69 (Z = 7.95, p < 0.001), and combined effect of ncADM and PRP was 5.28 (Z = 3.86, p < 0.001). These findings validate PRP as a clinical adjunct to enhance the native tissue response to implantable biomaterials and suggest that ncADM is more amenable than cADM to induced neovascularization. PRP use could be advantageous in patients undergoing VHR where poor incorporation is anticipated and early-enhanced neovascularization is desired.

Increased use of surgical energy promotes methicillin-resistant Staphylococcus aureus colonization in rabbits following open ventral hernia mesh repair.

BACKGROUND: Surgical energy has been widely implemented because of ease of use, effective hemostasis, and surgical dissection. Studies demonstrate its use to be an independent risk factor for postoperative wound infection. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common bacteria found in postoperative mesh infection. No reports are available on the sequelae of surgical energy use for open ventral hernia repair (oVHR) with mesh. We hypothesized that increasing amounts of surgical energy will result in higher infectious burden after oVHR with composite multifilament polyester mesh (Parietex™ PCO). METHODS: New Zealand rabbits underwent bridging oVHR with Parietex™ PCO and were divided into three surgical treatment groups: (1) scalpel alone, (2) 120 J of energy, and (3) 600 J of energy. The bioprosthesis was then inoculated with 105 colony-forming units of MRSA. Rabbits were survived for 7 days with daily physical examination. Complete blood count, basci metabolic panel, and blood cultures were performed on postoperative days one, four, and seven. Surviving rabbits were killed, and meshes explanted for MRSA colony counts. RESULTS: Rabbits receiving the most surgical energy developed signs and symptoms of severe sepsis and wound necrosis within 24 h. In comparison, rabbits receiving no surgical energy had significantly less MRSA recovered from explanted mesh, significantly less bacteremia, and fewer adhesions. CONCLUSIONS: Increased use of surgical energy promoted greater colonization, exaggerated septic response to bacterial contamination, and more severe adhesions. In the absence of devitalized tissue, rabbits can effectively limit bacterial contamination. These findings support the surgical principles of proper tissue handling and highlight the detrimental effects of indiscriminant surgical energy usage, thus emphasizing the importance of programs such as Fundamental Use of Surgical Energy.

Platelet rich plasma enhances tissue incorporation of biologic mesh.

BACKGROUND: High recurrence rates because of poor tissue incorporation limit the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Platelet rich plasma (PRP) is a growth factor-rich autologous blood product known to enhance tissue repair through cellular proliferation and neovascularization. We sought to study the effect of PRP on a porcine noncross-linked ADM in an in vivo model of VHR. We hypothesized that PRP would enhance ADM-tissue incorporation in a rat model of VHR. METHODS: Whole blood was extracted from Lewis rats followed by PRP isolation and characterization. Using a rat model of VHR, a noncross-linked ADM (Strattice) was implanted and activated PRP applied before closure. Rats were sacrificed at 2, 4, and 6 wk. Immunohistochemical staining of CD 31 on endothelial cells was used to quantify neovascularization. Hematoxylin eosin stained tissues were measured to quantify tissue deposition. RESULTS: Platelet concentration of PRP was standardized to 1 × 10(6) platelets/µL. Grossly, vessels were more evident in PRP-treated rats. Immunohistochemical analysis demonstrated neovascularization was significantly greater in the PRP-treated ADMs at all time points. This increase in neovascularization correlated with an increased thickness of tissue deposition at 4 and 6 wk. CONCLUSIONS: PRP enhanced neovascularization and incorporation in a rat model of VHR. Enhanced neovascularization was associated with earlier and greater tissue deposition on the ADM. This suggests that PRP could be used as an adjunct to VHR in clinical scenarios where poor wound healing is anticipated and enhanced neovascularization and early tissue deposition are desired.

Role of Resident Microbial Communities in Biofilm-Related Implant Infections: Recent Insights and Implications.

The use of medical implants continues to grow as the population ages. Biofilm-related implant infection is the leading cause of medical implant failure and remains difficult to diagnose and treat. Recent technologies have enhanced our understanding of the composition and complex functions of microbiota occupying various body site niches. In this review, we leverage data from molecular sequencing technologies to explore how silent changes in microbial communities from various sites can influence the development of biofilm-related infections. Specifically, we address biofilm formation and recent insights of the organisms involved in biofilm-related implant infections; how composition of microbiomes from skin, nasopharyngeal, and nearby tissue can impact biofilm-formation, and infection; the role of the gut microbiome in implant-related biofilm formation; and therapeutic strategies to mitigate implant colonization.

Restrictive Firearm Laws and Firearm-Related Suicide.

BACKGROUND: There were 23,854 suicides by firearms in 2017 in the US, accounting for 60% of all gun deaths. Studying firearm-related mortalities is vital for reducing preventable gun deaths. This study aims to determine the association between state-level presence of restrictive firearm laws and suicide rates with firearms. STUDY DESIGN: This ecological study used data from the CDC Wide-Ranging Online Data for Epidemiologic Research on decedents older than 18 years who died from intentional self-harm with firearms between 2009 and 2018. Exposures of interest were state-level restrictive firearm laws: background checks on private sales, mandatory waiting periods, and prohibited possession for domestic violence restraining orders or mental health red flags. Outcomes were rates of suicide with firearms per 100,000 persons over the 10-year period within each state. Welch's t -tests compared mean mortality rates in exposed and unexposed states. RESULTS: There were 208,621 deaths from intentional self-harm with firearms from 2009 to 2018. States with background checks, mandatory waiting periods, and prohibited possession were associated with lower suicide rates for all firearm types compared with states without these laws (p < 0.05). Only states with background checks and mandatory waiting periods were associated with lower suicide rates by handguns and large firearms (p < 0.05). CONCLUSION: Background checks and mandatory waiting periods correlated with fewer suicides by all firearms and specific firearm types. This reduction could be due to firearm laws directly preventing people from accessing guns or existing concurrently with other suicide prevention measures. More research should be directed to understanding how firearm laws can help reduce suicide rates.

State Firearm Laws and Rate of Assault-Related Firearm Death.

BACKGROUND: Studying firearm-related mortality is important to reduce preventable firearm death in the US. This study aims to determine the relationship between firearm laws and assault death with firearms. STUDY DESIGN: This ecologic study used public data from the CDC Wide-Ranging Online Data for Epidemiologic Research on decedents age 18 years or older who died from assault with firearms between 2009 and 2018 in all 50 states and Washington, DC. The outcomes were the rate of mortality per 100,000 persons from assault death by firearm used. Exposures of interest included the presence of 7 state firearm laws extracted from the RAND State Firearm Law Database. Welch's t tests were performed to compare mean mortality rate in states with each firearm law to states without each law. RESULTS: There were 114,945 deaths from assault with firearms from 2009 to 2018. States with "stand your ground" laws had a higher assault mortality rate from all firearms and from other/unspecified firearms than states without stand your ground laws (p = 0.026; p = 0.023). States with background checks for private sales of handguns and long guns had a lower assault mortality rate from handguns and rifles, shotguns, and large firearms, respectively, than states without either law (p = 0.019; p = 0.030). CONCLUSIONS: Stand your ground laws are correlated with a higher rate of gun-related assault death, but background checks on private sales are correlated with a lower rate. Future studies should elucidate the specific pathways by which state laws reduce, or fail to reduce, firearm-related assault death.

The impact of hypertonic saline on damage control laparotomy after penetrating abdominal trauma.

PURPOSE: The inability to achieve primary fascial closure (PFC) after emergency laparotomy increases the rates of adverse outcomes including fistula formation, incisional hernia, and intraabdominal infection. Hypertonic saline (HTS) infusion improves early PFC rates and decreases time to PFC in patients undergoing damage control laparotomy (DCL) after injury. We hypothesized that in patients undergoing DCL after penetrating abdominal injury, HTS infusion would decrease the time to fascial closure as well as the volume of crystalloid required for resuscitation without inducing clinically relevant acute kidney injury (AKI) or electrolyte derangements. METHODS: We retrospectively analyzed all penetrating abdominal injury patients undergoing DCL within the University of Pennsylvania Health System (January 2015-December 2018). We compared patients who received 3% HTS at 30 mL/h (HTS) to those receiving isotonic fluid (ISO) for resuscitation while the abdominal fascia remained open. Primary outcomes were the rate of early PFC (PFC within 72 h) and time to PFC; secondary outcomes included acute kidney injury, sodium derangement, ventilator-free days, hospital length of stay (LOS), and ICU LOS. Intergroup comparisons occurred by ANOVA and Tukey's comparison, and student's t, and Fischer's exact tests, as appropriate. A Shapiro-Wilk test was performed to determine normality of distribution. RESULTS: Fifty-seven patients underwent DCL after penetrating abdominal injury (ISO n = 41, HTS n = 16). There were no significant intergroup differences in baseline characteristics or injury severity score. Mean time to fascial closure was significantly shorter in HTS (36.37 h ± 14.21 vs 59.05 h ± 50.75, p = 0.02), and the PFC rate was significantly higher in HTS (100% vs 73%, p = 0.01). Mean 24-h fluid and 48-h fluid totals were significantly less in HTS versus ISO (24 h: 5.2L ± 1.7 vs 8.6L ± 2.2, p = 0.01; 48 h: 1.3L ± 1.1 vs 2.6L ± 2.2, p = 0.008). During the first 72 h, peak sodium (Na) concentration (146.2 mEq/L ± 2.94 vs 142.8 mEq/L ± 3.67, p = 0.0017) as well as change in Na from ICU admission (5.1 mEq/L vs 2.3, p = 0.016) were significantly higher in HTS compared to ISO. Patients in the HTS group received significantly more blood in the trauma bay compared to ISO. There were no intergroup differences in intraoperative blood transfusion volume, AKI incidence, change in chloride concentration (△Cl) from ICU admit, Na to Cl gradient (Na:Cl), initial serum creatinine (Cr), peak post-operative Cr, change in creatinine concentration (△Cr) from ICU admission, creatinine clearance (CrCl), initial serum potassium (K), peak ICU K, change in K from ICU admission, initial pH, highest or lowest post-operative pH, mean hospital LOS, ICU LOS, and ventilator-free days. CONCLUSIONS: HTS infusion in patients undergoing DCL after penetrating abdominal injury decreases the time to fascial closure and led to 100% early PFC. HTS infusion also decreased resuscitative fluid volume without causing significant AKI or electrolyte derangement. HTS appears to offer a safe and effective fluid management approach in patients who sustain penetrating abdominal injury and DCL to support early PFC without inducing measurable harm. LEVEL OF EVIDENCE: Level III.

Enterothecal fistula as a rare cause of adult pneumocephalus and meningitis: a case report.

Background: Enterothecal fistulas are pathological connections between the gastrointestinal system and subarachnoid space. These rare fistulas occur mostly in pediatric patients with sacral developmental anomalies. They have yet to be characterized in an adult born without congenital developmental anomaly yet must remain on the differential diagnosis when all other causes of meningitis and pneumocephalus have been ruled out. Good outcomes rely on aggressive multidisciplinary medical and surgical care, which are reviewed in this manuscript. Case Description: A 25-year-old female with history of a sacral giant cell tumor resected via anterior transperitoneal approach followed by posterior L4-pelvis fusion presented with headaches and altered mental status. Imaging revealed that a portion of small bowel had migrated into her resection cavity and created an enterothecal fistula resulting in fecalith within the subarachnoid space and florid meningitis. The patient underwent a small bowel resection for fistula obliteration, and subsequently developed hydrocephalus requiring shunt placement and two suboccipital craniectomies for foramen magnum crowding. Ultimately, her wounds became infected requiring washouts and instrumentation removal. Despite a prolonged hospital course, she made significant recovery and at 10-month following presentation, she is awake, oriented, and able to participate in activities of daily living. Conclusions: This is the first case of meningitis secondary to enterothecal fistula in a patient without a previous congenital sacral anomaly. Operative intervention for fistula obliteration is the primary treatment and should be performed at a tertiary hospital with multidisciplinary capabilities. If recognized quickly and appropriately treated, there is a possibility of good neurological outcome.

Nanotechnologies and regenerative medical approaches for space and terrestrial medicine.

One purpose of the International Space Station (ISS) is to explore powerful new areas of biomedical science in microgravity. Recent advances in nanotechnology applied to medicine--what we now refer to as nano-medicine--and regenerative medicine have enormous untapped potential for future space and terrestrial medical applications. Novel means for drug delivery and nanoscale screening tools will one day benefit astronauts venturing to Mars and places beyond, while the space laboratory will foster advances in nanotechnologies for diagnostic and therapeutic tools to help our patients here on Earth. Herein we review a series of nanotechnologies and selected regenerative medical approaches and highlight key areas of ongoing and future investigation that will benefit both space and terrestrial medicine. These studies target significant areas of human disease such as osteoporosis, diabetes, radiation injury, and many others.

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

INTRODUCTION: Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. METHODS: A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. RESULTS: 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). CONCLUSION: Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.

Four Columns of the Thorax: Operative Decision-Making in the Setting of Complete Bony Instability.

Thoracic skeletal injury is a common outcome of motor vehicle accidents. Skeletal reconstruction is guided by anatomic and physiologic variables dictated by the injury complex. Here we describe a report of a patient who sustained complex trauma to the thorax leading to complete thoracic dissociation. Clinical and operative decision-making is discussed to inform the reader of a proposed ordered protocol and considerations for operative intervention and reconstruction.

Actionable Risk Model for the Development of Surgical Site Infection after Emergency Surgery.

Background: Surgical site infections (SSIs) increase mortality and the economic burden associated with emergency surgery (ES). A reliable and sensitive scoring system to predict SSIs can help guide clinician assessment and patient counseling of post-operative SSI risk. We hypothesized that after quantifying the ES post-operative SSI incidence, readily abstractable parameters can be used to develop an actionable risk stratification scheme. Patients and Methods: We reviewed retrospectively all patients who underwent ES operations at an urban academic hospital system (2005-2013). Comorbidities and operative characteristics were abstracted from the electronic health record (EHR) with a primary outcome of post-operative SSIs. Risk of SSI was calculated using logistic regression modeling and validated using bootstrapping techniques. Beta-coefficients were calculated to correlate risk. A simplified clinical risk assessment tool was derived by assigning point values to the rounded ß-coefficients. Results: A total of 4,783 patients with a 13.2% incidence of post-operative SSIs were identified. The strongest risk factors associated with SSIs included acute intestinal ischemia, weight loss, intestinal perforation, trauma-related laparotomy, radiation exposure, previous gastrointestinal surgery, and peritonitis. The assessment tool defined three patient groups based on SSI risk. Post-operative SSI incidence in high-risk patients (34%; score = 6-10) exceeded that of medium- (11.1%; score = 3-5) and low-risk patients (1.5%; score = 1-2) (C statistic = 0.802). Patients with a risk score ≥10 points evidenced the highest post-operative SSI risk (71.9%). Conclusion: Pre-operative identification of ES patient risk for post-operative SSI may inform pre-operative patient counseling and operative planning if the proposed procedure includes medical device implantation. A clinically relevant seven-factor risk stratification model such as this empirically derived one may be suitable to incorporate into the EHR as a decision-support tool.

Amniotic fluid allograft enhances the host response to ventral hernia repair using acellular dermal matrix.

Ventral hernia repair (VHR) with acellular dermal matrix (ADM) has high rates of recurrence that may be improved with allogeneic growth factor augmentation such as amniotic fluid allograft (AFA). We hypothesized that AFA would modulate the host response to improve ADM incorporation in VHR. Lewis rats underwent chronic VHR with porcine ADM alone or with AFA augmentation. Tissue harvested at 3, 14, or 28 days was assessed for region-specific cellularity, and a validated histomorphometric score was generated for tissue incorporation. Expression of pro-inflammatory (Nos1, Tnfα), anti-inflammatory (Arg1, Il-10, Mrc1) and tissue regeneration (Col1a1, Col3a1, Vegf, and alpha actinin-2) genes were quantified using quantitative reverse-transcription polymerase chain reaction. Amniotic fluid allograft treatment caused enhanced vascularization and cellularization translating to increased histomorphometric scores at 14 days, likely mediated by upregulation of pro-regeneration genes throughout the study period and molecular evidence of anti-inflammatory, M2-polarized macrophage phenotype. Collectively, this suggests AFA may have a therapeutic role as a VHR adjunct.

Improved Posterolateral Lumbar Spinal Fusion Using a Biomimetic, Nanocomposite Scaffold Augmented by Autologous Platelet-Rich Plasma.

Remodeling of the human bony skeleton is constantly occurring with up to 10% annual bone volume turnover from osteoclastic and osteoblastic activity. A shift toward resorption can result in osteoporosis and pathologic fractures, while a shift toward deposition is required after traumatic, or surgical injury. Spinal fusion represents one such state, requiring a substantial regenerative response to immobilize adjacent vertebrae through bony union. Autologous bone grafts were used extensively prior to the advent of advanced therapeutics incorporating exogenous growth factors and biomaterials. Besides cost constraints, these applications have demonstrated patient safety concerns. This study evaluated the regenerative ability of a nanostructured, magnesium-doped, hydroxyapatite/type I collagen scaffold (MHA/Coll) augmented by autologous platelet-rich plasma (PRP) in an orthotopic model of posterolateral lumbar spinal fusion. After bilateral decortication, rabbits received either the scaffold alone (Group 1) or scaffold with PRP (Group 2) to the anatomic right side. Bone regeneration and fusion success compared to internal control were assessed by DynaCT with 3-D reconstruction at 2, 4, and 6 weeks postoperatively followed by comparative osteogenic gene expression and representative histopathology. Both groups formed significantly more new bone volume than control, and Group 2 subjects produced significantly more trabecular and cortical bone than Group 1 subjects. Successful fusion was seen in one Group 1 animal (12.5%) and 6/8 Group 2 animals (75%). This enhanced effect by autologous PRP treatment appears to occur via astounding upregulation of key osteogenic genes. Both groups demonstrated significant gene upregulation compared to vertebral bone controls for all genes. Group 1 averaged 2.21-fold upregulation of RUNX2 gene, 3.20-fold upregulation of SPARC gene, and 3.67-fold upregulation of SPP1 gene. Depending on anatomical subgroup (cranial, mid, caudal scaffold portions), Group 2 had significantly higher average expression of all genes than both control and Group 1-RUNX2 (8.23-19.74 fold), SPARC (18.67-55.44 fold), and SPP1 (46.09-90.65 fold). Our data collectively demonstrate the osteoinductive nature of a nanostructured MHA/Coll scaffold, a beneficial effect of augmentation with autologous PRP, and an ability to achieve clinical fusion when applied together in an orthotopic model. This has implications both for future study and biomedical innovation of bone-forming therapeutics.

Polyester Mesh Functionalization with Nitric Oxide-Releasing Silica Nanoparticles Reduces Early Methicillin-Resistant Staphylococcus aureus Contamination.

Background: Infected hernia mesh is a cause of post-operative morbidity. Nitric oxide (NO) plays a key role in the endogenous immune response to infection. We sought to study the efficacy of a NO-releasing mesh against methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that a NO-releasing polyester mesh would decrease MRSA colonization and proliferation. Materials and Methods: A composite polyester mesh functionalized with N-diazeniumdiolate silica nanoparticles was synthesized and characterized. N-diazeniumdiolate silica parietex composite (NOSi) was inoculated with 104,106, or 108 colony forming units (CFUs) of MRSA and a dose response was quantified in a soy tryptic broth assay. Utilizing a rat model of contaminated hernia repair, implanted mesh was inoculated with MRSA, recovered, and CFUs were quantified. Clinical metrics of erythema, mesh contracture, and adhesion severity were then characterized. Results: Methicillin-resistant Staphylococcus aureus CFUs demonstrated a dose-dependent response to NOSi in vitro. In vivo, quantified CFUs showed a dose-dependent response to NOSi-PCO. Treated rats had fewer severe adhesions, less erythema, and reduced mesh contracture. Conclusions: We demonstrate the efficacy of a NO-releasing mesh to treat MRSA in vitro and in vivo. Creation of a novel class of antimicrobial prosthetics offers new strategies for reconstructing contaminated abdominal wall defects and other procedures that benefit from deploying synthetic prostheses in contaminated environments.

Platelet-rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair.

Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest. Still these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by the synthetic materials. Platelet-rich plasma (PRP), a growth-factor-rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease the rates of recurrence. Here, we demonstrate that PRP promotes the release of growth factors stromal derived factor (SDF)-1, transforming growth factor-beta, and platelet-derived growth factor in a dose-dependent manner. Additionally, we utilize an aortic ring angiogenesis assay to show that PRP promotes angiogenesis in vitro. A rat model of VHR using StratticeTM ADM demonstrates similar findings in vivo, corresponding with the increased expression of vascular endothelial growth factor and collagen type 1 alpha 1. Finally, we show that the molecular and cellular activity initiated by PRP results in an increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an essential step in demonstrating the utility and the mechanism of platelet-derived plasma in biomaterial-aided wound healing and provide promising preclinical data that suggest such materials may improve surgical outcomes.

Addition of platelet-rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model.

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.