Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection

• Published in: Nature communications 2019-10, Vol.10 (1), p.4830-12, Article 4830
• Main Authors: D’Amato, Anthony R., Puhl, Devan L., Ellman, Samuel A. T., Balouch, Bailey, Gilbert, Ryan J., Palermo, Edmund F.
• Format: Article
• Language: English
• Subjects: 14/19; 147/135; 17β-Estradiol; 631/154/309; 639/301/54; 639/638/455; 692/700/565/1436/152; Animals; Animals, Newborn; Astrocytes - drug effects; Biocompatible Materials; Biological activity; Biomaterials; Biomedical materials; Central nervous system; Central Nervous System Agents - administration & dosage; Central Nervous System Agents - chemistry; Central Nervous System Agents - pharmacology; Contact angle; Drug delivery systems; Drug Implants - chemistry; Drugs; Estradiol - administration & dosage; Estradiol - chemistry; Estradiol - pharmacology; Estrogens; Estrogens - administration & dosage; Estrogens - chemistry; Estrogens - pharmacology; Ganglia, Spinal - drug effects; Humanities and Social Sciences; In Vitro Techniques; Injuries; Macrophages; Mechanical properties; Molecular weight; multidisciplinary; Nervous system; Neuronal Outgrowth - drug effects; Neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Polyesters; Polymerization; Polymers; Polymers - chemistry; Primary Cell Culture; Prodrugs - administration & dosage; Prodrugs - chemistry; Prodrugs - pharmacology; Rats; Scaffolds; Science; Science (multidisciplinary); Sex hormones; Spinal Cord - cytology; Surgical implants; Thin films; Tropism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12835-w

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1–10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential. Currently there are no therapeutics for long lasting central nervous system injuries, that can address the complex injury cascade that develops over years. Here the authors report biomaterial scaffolds that release 17β-estradiol (E2) at nanomolar concentrations over the course of 1–10 years via slow hydrolysis in vitro.