The utility of hydrogels for regenerative medicine can be improved through localized gene delivery to enhance their bioactivity. However, current systems typically lead to low-level transgene expression located in host tissue surrounding the implant. Herein, we investigated the inclusion of macropores into hydrogels to facilitate cell ingrowth and enhance gene delivery within the macropores in vivo. Macropores were created within PEG hydrogels by gelation around gelatin microspheres, with gelatin subsequently dissolved by incubation at 37°C. The macropores were interconnected, as evidenced by homogeneous cell seeding in vitro and complete cell infiltration in vivo. Lentivirus loaded within hydrogels following gelation retained its activity relative to the unencapsulated control virus. In vivo, macroporous PEG demonstrated sustained, elevated levels of transgene expression for 6 weeks, while hydrogels without macropores had transient expression. Transduced cells were located throughout the macroporous structure, while non-macroporous PEG hydrogels had transduction only in the adjacent host tissue. Delivery of lentivirus encoding for VEGF increased vascularization relative to the control, with vessels throughout the macropores of the hydrogel. The inclusion of macropores within the hydrogel to enhance cell infiltration enhances transduction and influences tissue development, which has implications for multiple regenerative medicine applications.

Background:The aim of this study was to define the rate of new persistent opioid use and risk factors for persistent opioid use after operative and nonoperative treatment of ankle fractures.Methods:Using a nationwide insurance claims database, Clinformatics DataMart Database, we identified opioid-naïve patients who underwent surgical treatment of unstable ankle fracture patterns between January 2009 and June 2016. Patients who underwent closed treatment of a distal fibula fracture served as a comparative group. We evaluated peritreatment and posttreatment opioid prescription fills. The primary outcome, new persistent opioid use, was defined as opioid prescription fulfillment between 91 and 180 days after the procedure. Logistic regression was used to evaluate the effect of patient factors, and the differences of the effect were tested using Wald statistics. The adjusted persistent use rates were calculated. A total of 13 088 patients underwent treatment of an ankle fracture and filled a peritreatment opioid prescription.Results:When compared with closed treatment of a distal fibula fracture, only 2 surgical treatment subtypes demonstrated significantly increased rates of persistent use compared with the closed treatment group: open treatment of bimalleolar ankle fracture (adjusted odds ratio [aOR], 1.32; 95% CI, 1.10-1.58; P = .002) and open treatment of trimalleolar ankle fracture with fixation of posterior lip (aOR, 1.47; 95% CI, 1.04-2.07; P = .027). Rates were significantly increased (aOR, 1.56; 95% CI, 1.34-1.82; P < .001) among patients who received a total peritreatment opioid dose that was in the top 25th percentile of total oral morphine equivalents. Factors independently associated with new persistent opioid use included mental health disorders, comorbid conditions, tobacco use, and female sex.Conclusion:All ankle fracture treatment groups demonstrated high rates of new persistent opioid use, and persistent use was not directly linked to injury severity. Instead, we identified patient factors that demonstrated increased risk of persistent opioid use. Limiting the peritreatment opioid dose was the largest modifiable risk factor related to new persistent opioid use in this privately insured cohort.Level of Evidence:Level III, retrospective cohort study.

Background: Orthopaedic surgeons are the fourth highest on the list of top prescribers of opioid analgesics by specialty and have a direct impact on opioid-related morbidity in the United States. Operative bunion correction is one of the most commonly performed elective foot surgical procedures in this country. We sought to determine the rate of new persistent opioid use following exposure to opioids after surgical treatment of hallux valgus (bunionectomy) and to identify associated risk factors. Methods: A nationwide U.S. insurance claims database, Truven Health MarketScan, was used to identify opioid-naïve patients who underwent surgical treatment of hallux valgus employing 3 common procedures from January 2010 to June 2015. The rate of new persistent opioid use (i.e., fulfillment of an opioid prescription between 91 and 180 days after the surgical procedure) among patients who filled a perioperative opioid prescription was then calculated. A logistic regression model was used to examine the relationship between new persistent use and risk factors, including surgical procedure, patient demographic characteristics, and patient comorbidities. Results: A total of 36,562 patients underwent surgical treatment of hallux valgus and filled a perioperative opioid prescription. The rate of new persistent opioid use among all patients who filled a perioperative opioid prescription was 6.2%. Patients who underwent treatment with a first metatarsal-cuneiform arthrodesis were more likely to have new persistent opioid use compared with the distal metatarsal osteotomy control group (adjusted odds ratio, 1.19 [95% confidence interval, 1.03 to 1.39]; p = 0.021). Factors independently associated with new persistent opioid use included prescribing patterns, coexisting mental health diagnoses, and certain pain disorders. Conclusions: New persistent opioid use following surgical treatment of hallux valgus affects a substantial number of patients. Understanding factors associated with persistent opioid use can help clinicians to identify and counsel at-risk patients and to mitigate this public health crisis. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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Category: Bunion Introduction/Purpose: Chronic opioid use and abuse is one of the greatest public health challenges in the United States and continues to worsen. Orthopaedic surgeons stand at #4 on the list of top prescribers of opioid analgesics by specialty and are squarely positioned to have an impact on the problem. A recent study revealed an 8% prevalence of new persistent opioid usage following abdominal surgery. At present, the incidence of persistent opioid use after foot and ankle surgery is largely unknown. Operative bunion correction is one of the most commonly performed elective foot and ankle surgeries in this country. We sought to determine the incidence of new persistent opioid use following surgical treatment of hallux valgus and to identify patient factors associated with persistent opioid use. Methods: A nationwide insurance claims data set from January 2010 to June 2015 was used to identify opioid naive patients (defined as patients with no prior opioid use 12 months prior to injury) who underwent surgical treatment of hallux valgus with either a proximal or distal first metatarsal osteotomy. The incidence of new persistent opioid use, defined by opioid prescription fulfillment between 90 and 180 days after surgery was then calculated. Data were assessed for patient factors which may be predictors of new persistent opioid use including surgery type, health insurance type, age, gender, household income, and comorbidities. Results: A total of 38,312 patients underwent surgical treatment of hallux valgus with either a distal or proximal first metatarsal osteotomy and filled a perioperative opioid prescription. The rate of new persistent opioid use among all patients was 5.6%. The majority of patients (90%) underwent treatment with a distal metatarsal osteotomy. Patients who underwent treatment with a proximal metatarsal osteotomy were more likely to have new persistent opioid use (aOR: 1.16; p=0.04). Logistic regression analysis demonstrated that patient factors independently associated with new persistent opioid use included depression, anxiety, alcohol and substance abuse disorders, and certain preoperative pain disorders. Age, gender, and income were not associated with new persistent opioid use. Conclusion: Despite rising national attention, opioid abuse continues to be a growing epidemic. In order for foot and ankle surgeons to help solve this problem, it must first be better defined. New persistent opioid use following surgical treatment of hallux valgus affects a substantial, growing number of patients. Fifty percent of patients using opioids for 3 months will be using them at 5 years. Understanding patient factors associated with persistent opioid use can help clinicians identify and counsel at-risk patients and ultimately focus strategies and interventions aimed at mitigating and eliminating this massive public health problem.