The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals, and plastics, significantly abrogated foreign body reactions and fibrosis when compared to smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5 mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than 5-fold longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved by simply tuning their spherical dimensions.
The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient1–6. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.
Host recognition and immune-mediated foreign body response (FBR) to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knock out and CXCL13 neutralization. Interestingly, Colony Stimulating Factor-1 Receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer, and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, ROS production, and phagocytosis. Our results indicate targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.
We used our pilot audit to target specific information that was commonly omitted and we 'enforced' these areas using drop-down selections in electronic operation note. This study has demonstrated that implementation of an electronic operation note system markedly improved the quality of documentation, both in terms of information detail and readability. We would recommend this template system as a standard for operation note documentation.
Assess the effects of cryopreservation (cryo) and vitrification (vitro) on the viscoelastic properties of blood vessels. Human external Iliac artery vessels were harvested from liver organ donors (n=8). In each case the vessel was segmented into 3 equal parts, which were randomly placed in one of 3 categories: Fresh (stored in 4 degrees C UW for 6 h), Cryo (Placed in 10% Dulbecco's modified Eagle medium (DMEM) and slowly frozen to -196 degrees C), or Vitro (Placed in 40% DMEM and rapidly cooled to -196 degrees C). A pulsatile flow circuit was used to perfuse arterial segments at physiological pulse pressure and flow. Intraluminal pressure was measured using a Millar Mikro-tip catheter transducer, and vessel wall motion was determined with duplex ultrasonography coupled with a novel echo-locked vessel wall tracking system. Diametrical compliance (DC), Petersons elastic modulus (Ep), and stiffness index (beta) were then calculated for each of the three groups over 3 mean pressure ranging from 40 to 80 mmHg. The change in the viscous component of arterial wall (lag phase angle, theta) was calculated from hysteresis plots. No significant changes were observed in the elastic properties of fresh and vitrified vessels (P>0.05 for each of DC, Ep, and beta). Similarly, variation in the wall viscosity between fresh and vitrified vessels appeared to be nonsignificant (theta=12.60+/-4.04 vs. 17.60+/-1.14, respectively). In contrast, statistical analysis of results obtained for cryopreserved vessels to the fresh vessels showed significant reduction in elastic parameter values. There was also a significant increase in the phase angle theta of the cryopreserved vessels (theta=24.30+/-6.32; P<0.001) compared with fresh vessel. Results suggest that vitrification maintains both elastic and viscous components of the mechanical properties of vascular grafts, which is positively correlated with their functional patency. In contrast, damage caused during cryopreservation significantly affects the overall tensile strength and elasticity of the vessel (i.e., Ep and beta), the dynamic properties (DC), and appears to significantly affect the viscous component of the vessel wall (theta), which is likely reduce the patency of the graft for transplantation purposes.
Benign Triton tumor (neuromuscular choristoma) is a rare mass that most commonly occurs as a multinodular expansion of tissue in or around large nerves. Intracranial occurrence is uncommon. We report on a 4-year-old girl presenting with a right-sided facial mass and trismus. Imaging revealed a large, complex mass extending from the ventral aspect of the pons, along the trigeminal nerve, through the foramen ovale, and into the right infratemporal fossa. The lesion was partially enhancing, invaded adjacent infratemporal musculature, was associated with marked overgrowth of the right coronoid process, and induced bony erosion of the middle cranial fossa. After needle biopsy, a multidisciplinary team, including plastic surgery, otolaryngology, and neurosurgery, performed a combined, multistep, single-day surgical approach for resection. Unique to this case was the resection of the coronoid process, a modified middle fossa intradural and extradural approach, coupled with a transfacial infratemporal approach. Microscopically, the resected tissue showed skeletal muscle, fibrous tissue, and nerve in a disorganized arrangement characteristic of a benign Triton tumor. We present this case to illustrate diagnostic clues and pitfalls in the preoperative evaluation of a benign Triton tumor. We also highlight the pathologist's role as a partner in a multidisciplinary approach to diagnosis and treatment of this rare pediatric mass, potentially the largest Triton tumor in the head reported to date.
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