RESUMEN
The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. 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.
Asunto(s)
Cuerpos Extraños/inmunología , Reacción a Cuerpo Extraño/inmunología , Hidrogeles/uso terapéutico , Prótesis e Implantes/efectos adversos , Animales , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/uso terapéutico , Humanos , Hidrogeles/efectos adversos , Macrófagos/inmunología , Primates/inmunologíaRESUMEN
A 30-year-old, right-handed female presented 2 weeks postpartum with acute-onset severe headache, vertigo, and vomiting. Initial neurologic examination illustrated lingual dysarthria, horizontal nystagmus, right dysmetria on finger-to-nose testing, and weakness of the extremities. Magnetic resonance imaging showed a large, left lateral medullary infarction (Wallenberg syndrome) with cephalad extension into the ipsilateral pons as well as involvement of the left middle cerebellar peduncle. The patient was discharged 3 weeks later to an inpatient rehabilitation facility with gradual improvement of her symptoms.
RESUMEN
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 with 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 five times 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 simply by tuning their spherical dimensions.
Asunto(s)
Reacción a Cuerpo Extraño/inmunología , Animales , Ratones , Ratones Endogámicos C57BL , PrimatesRESUMEN
Islets microencapsulation holds great promise to treat type 1 diabetes. Currently used alginate microcapsules often have islets protruding outside capsules, leading to inadequate immuno-protection. A novel design of microcapsules with core-shell structures using a two-fluid co-axial electro-jetting is reported. Improved encapsulation and diabetes correction is achieved in a single step by simply confining the islets in the core region of the capsules.