Major limitations of current tissue regeneration approaches using artificial scaffolds are fibrous encapsulation, lack of host cellular infiltration, unwanted immune responses, surface degradation preceding biointegration, and artificial degradation byproducts. Specifically, for scaffolds larger than 200 500 μm, implants must be accompanied by host angiogenesis in order to provide adequate nutrient/waste exchange in the newly forming tissue. In the current work, we design a peptide-based self-assembling nanofibrous hydrogel containing cell-mediated degradation and proangiogenic moieties that specifically address these challenges. This hydrogel can be easily delivered by syringe, is rapidly infiltrated by cells of hematopoietic and mesenchymal origin, and rapidly forms an extremely robust mature vascular network. scaffolds show no signs of fibrous encapsulation and after 3 weeks are resorbed into the native tissue. These supramolecular assemblies may prove a vital paradigm for tissue regeneration and specifically for ischemic tissue disease.

Delivery of small molecules and drugs to tissues is a mainstay of several tissue engineering strategies. Next generation treatments focused on localized drug delivery offer a more effective means in dealing with refractory healing when compared to systemic approaches. Here we describe a novel multidomain peptide hydrogel that capitalizes on synthetic peptide chemistry, supramolecular self-assembly and cytokine delivery to tailor biological responses. This material is biomimetic, shows shear stress recovery and offers a nanofibrous matrix that sequesters cytokines. The biphasic pattern of cytokine release results in the spatio-temporal activation of THP-1 monocytes and macrophages. Furthermore, macrophage-material interactions are promoted without generation of a proinflammatory environment. Subcutaneous implantation of injectable scaffolds showed a marked increase in macrophage infiltration and polarization dictated by cytokine loading as early as 3 days, with complete scaffold resorption by day 14. Macrophage interaction and response to the peptide composite facilitated the (i) recruitment of monocytes/macrophages, (ii) sustained residence of immune cells until degradation, and (iii) promotion of a pro-resolution M2 environment. Our results suggest the potential use of this injectable cytokine loaded hydrogel scaffold in a variety of tissue engineering applications.

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G′ and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype.

For a proangiogenic therapy to be successful, it must promote the development of mature vasculature for rapid reperfusion of ischemic tissue. Whole growth factor, stem cell, and gene therapies have yet to achieve the clinical success needed to become FDA-approved revascularization therapies. Herein, we characterize a biodegradable peptide-based scaffold engineered to mimic VEGF and self-assemble into a nanofibrous, thixotropic hydrogel, SLanc. We found that this injectable hydrogel was rapidly infiltrated by host cells and could be degraded while promoting the generation of neovessels. In mice with induced hind limb ischemia, this synthetic peptide scaffold promoted angiogenesis and ischemic tissue recovery, as shown by Doppler-quantified limb perfusion and a treadmill endurance test. Thirteen-month-old mice showed significant recovery within 7 days of treatment. Biodistribution studies in healthy mice showed that the hydrogel is safe when administered intramuscularly, subcutaneously, or intravenously. These preclinical studies help establish the efficacy of this treatment for peripheral artery disease due to diminished microvascular perfusion, a necessary step before clinical translation. This peptide-based approach eliminates the need for cell transplantation or viral gene transfection (therapies currently being assessed in clinical trials) and could be a more effective regenerative medicine approach to microvascular tissue engineering.

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism forradiation brain necrosis development. Bevacizumab alleviates brain edema symptoms caused by radiation brain necrosis through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients’ Karnofsky performance status (KPS) scores and brain necrosis imaging. However, necrosis is irreversible, and hypoxia and ischemia localized in the brain necrosis area may easily lead to radiation brain necrosis recurrence after bevacizumab is discontinued. Further studies are necessary to investigate brain necrosis diagnoses, bevacizumab indications, and the optimal mode of administration, bevacizumab resistance and necrosis with a residual or recurrent tumor.

OBJECTIVE Chronic subdural hematoma (CSDH) is commonly encountered in neurosurgical practice. However, surgical evacuation remains complicated by a high rate of reoperation. The optimal surgical approach to reduce the reoperation rate has not been determined. In the current study, the authors evaluated the prognostic value of clinical and radiographic factors to predict reoperation in the context of CSDH. METHODS A retrospective review of 325 CSDH patients admitted to an academic medical center in the United States, between 2006 and 2016, was performed. Clinical and radiographic factors predictive of the need for CSDH reoperation were identified on univariable and multivariable analyses. RESULTS Univariable analysis showed that warfarin use, clopidogrel use, mixed hypo- and isointensity on T1-weighted MRI, greater preoperative midline shift, larger hematoma/fluid residual on first postoperative day CT, lesser decrease in hematoma size after surgery, use of monitored anesthesia care (MAC), and lack of intraoperative irrigation correlated with a significantly higher rate of reoperation. Multivariable analysis, however, showed that only the presence of loculation, clopidogrel or warfarin use, and percent of hematoma change after surgery significantly predicted the need for reoperation. Our results showed that 0% (no reduction), 50%, and 100% hematoma maximum thickness change (complete resolution of hematoma after surgery) were associated with a 41%, 6%, and < 1% rate of reoperation, respectively. The use of drains, either large diameter or small caliber, did not have any effect on the likelihood of reoperation. CONCLUSIONS Among many factors, clopidogrel or warfarin use, hematoma loculation on preoperative CT, and the amount of hematoma evacuation on the first postoperative CT were the strongest predictors of reoperation.

ObjectiveTo investigate the treatment efficacy of ultra-low-dose bevacizumab for cerebral radiation necrosis.MethodsPatients with cerebral radiation necrosis after stereotactic radiotherapy (SRT) confirmed by imaging were included. Bevacizumab (1 mg/kg, once every three weeks, for at least three continuous treatments) was administered. The primary endpoints included change in cerebral necrosis symptoms, volume of intracranial edema, and changes in MRI signals. The secondary endpoints were adverse reactions of bevacizumab treatment.ResultsIn total, 21 patients were included in this study, all of whom received SRT between December 2016 and February 2019, developed cerebral radiation necrosis, and were treated with bevacizumab. Twenty patients were symptomatic from radiation necrosis, and the symptoms were alleviated in 18 patients (90%). Twenty patients had intracranial edema, and the grade of edema index (EI) was improved in 19 patients (95%). The intensity of the intracranial-enhanced MRI signals was significantly reduced in 20 patients (95.24%). The adverse reactions of bevacizumab treatment were mild, and no adverse reactions more severe than grade 2 were found.ConclusionThe preliminary results showed that ultra-low-dose bevacizumab had high efficacy for treating cerebral radiation necrosis, and could be a valid alternative to the standard-dose bevacizumab.Clinical registryChinese clinical trial registry (ChiCTR-IOD-16009803).

Using the adiabatic trajectory method, the migration energy barriers for the migration of Li ions and Cr ions along the one-dimensional diffusion pathway in pure and Cr doped LiFePO4 are obtained from first principles calculations. The results show that while Li ions can diffuse along the diffusion pathway easily, Cr ions do not easily diffuse away from their initial positions. This means that the heavy Cr ions will block the one-dimensional diffusion pathway of the material. Monte Carlo simulations are performed to evaluate the influences of the blocking behaviours on the electrochemical performance of LiFePO4 cathode material for Li ion secondary batteries. The results show that the evaluated capacity is highly sensitive to the amount of the dopant, the size of the super-cell being used for simulation (particle size of the powder cathode material) and the Monte Carlo steps for statistics (charge–discharge current density).