First, a novel nanomaterial-templated protein assembly (NTPA) method is reported for synthesizing protein nanoscaffolds. Protein bioscaffolds are advantageous for drug delivery and tissue engineering because they are biocompatible, biodegradable, programmable, and self-therapeutic. However, the challenge with using proteins to create 3D scaffolds is that this only works for a subset of proteins with specific secondary structures (such as amyloid beta sheets), or by modifying proteins with cross-linkable ligands, which can compromise their biological properties. Modifying the drug release profile in IVDD treatments also requires alteration of the porosity of protein scaffolds without varying the protein functionalities. To this end, Dr. Lee’s lab proposed and verified a novel NTPA strategy by first non-covalently immobilizing proteins to rigid biodegradable 2D nanomaterial (MnO2 nanosheets) and then co-assembly with cationic polymers into 3D porous protein nanoscaffolds followed by degradation of the rigid nanomaterial templates. Although gelatin nanoscaffolds were produced as proof-of-concept, this NTPA strategy has the potential to be used for various proteins without modifying their chemical structures or biological functions.
Second, nanoscaffold-based long-lasting ROS and cf-NA scavenging was proposed and tested for effective anti-inflammatory therapy. Dysregulated immune cell responses can lead to chronic inflammation, which is linked to various severe medical conditions, including disc degeneration. However, current drug-based anti-inflammatory strategies are often limited in achieving long-term therapeutic effects. By designing self-therapeutic nanoscaffolds that scavenge two crucial pro-inflammatory stimuli (ROS and cf-NA), long-lasting anti-inflammatory outcomes were realised by nanoscaffold alone.
Last, a synergy is discovered between epigenetic modulator delivery and the self-therapeutic nanoscaffold for pain reduction and disc degeneration. Pain reduction and disc regeneration are two of the most important challenges in treating intervertebral disc injuries. Recent evidence revealed that epigenetics plays a crucial role in disc degeneration. For the first time, sustainable delivery of epigenetic modulators with self-therapeutic nanoscaffolds was tested for anti-inflammation, pain reduction, and disc regeneration after disc injuries. This strategy could pave the way for the treatment of severe injuries and diseases of the intervertebral disc.
Continually, by working with biologists and clinicians, Dr. Lee’s lab will continue to improve the current system for applications in fibrocartilaginous tissue engineering for better patient treatment.
PUBLICATION: This work was recently published in Advanced Materials, 2023, https://doi.org/10.1002/adma.202303021
AUTHORS: Letao Yang, Basanta Bhujel, Yannan Hou, Jeffrey Luo, Seong Bae An, Inbo Han, Ki-Bum Lee
CORRESPONDENCE: Prof. Ki-Bum Lee (Rutgers University), https://kblee.rutgers.edu/
KBLEE Group Team: Dr. Letao Yang, Yannan Hou, Dr. Jeffrey Luo, https://kblee.rutgers.edu/