Degeneration of fibrocartilaginous tissues is often associated with complex pro‐inflammatory factors. These include reactive oxygen species (ROS), cell‐free nucleic acids (cf‐NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all‐in‐one nanoscaffold‐based 3D porous hybrid protein (3D‐PHP) self‐therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D‐PHP nanoscaffold is synthesized by introducing a novel nanomaterial‐templated protein assembly (NTPA) strategy. 3D‐PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli‐responsive drug release, disc‐mimetic stiffness, and excellent biodegradability. Enzyme‐like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf‐NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D‐PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long‐term pain reduction. Therefore, self‐therapeutic and epigenetic modulator‐encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.
Central nervous system (CNS) injuries are often debilitating, and most currently have no cure. This is due to the formation of a neuroinhibitory microenvironment at injury sites, which includes neuroinflammatory signaling and non‐permissive extracellular matrix (ECM) components. To address this challenge, a viscous interfacial self‐assembly approach, to generate a bioinspired hybrid 3D porous nanoscaffold platform for delivering anti‐inflammatory molecules and establish a favorable 3D‐ECM environment for the effective suppression of the neuroinhibitory microenvironment, is developed. By tailoring the structural and biochemical properties of the 3D porous nanoscaffold, enhanced axonal growth from the dual‐targeting therapeutic strategy in a human induced pluripotent stem cell (hiPSC)‐based in vitro model of neuroinflammation is demonstrated. Moreover, nanoscaffold‐based approaches promote significant axonal growth and functional recovery in vivo in a spinal cord injury model through a unique mechanism of anti‐inflammation‐based fibrotic scar reduction. Given the critical role of neuroinflammation and ECM microenvironments in neuroinhibitory signaling, the developed nanobiomaterial‐based therapeutic intervention may pave a new road for treating CNS injuries.more » « less
- Award ID(s):
- NSF-PAR ID:
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Purpose of Review
Interfacial tissue exists throughout the body at cartilage-to-bone (osteochondral interface) and tendon-to-bone (enthesis) interfaces. Healing of interfacial tissues is a current challenge in regenerative approaches because the interface plays a critical role in stabilizing and distributing the mechanical stress between soft tissues (e.g., cartilage and tendon) and bone. The purpose of this review is to identify new directions in the field of interfacial tissue development and physiology that can guide future regenerative strategies for improving post-injury healing.
Cues from interfacial tissue development may guide regeneration including biological cues such as cell phenotype and growth factor signaling; structural cues such as extracellular matrix (ECM) deposition, ECM, and cell alignment; and mechanical cues such as compression, tension, shear, and the stiffness of the cellular microenvironment.
In this review, we explore new discoveries in the field of interfacial biology related to ECM remodeling, cellular metabolism, and fate. Based on emergent findings across multiple disciplines, we lay out a framework for future innovations in the design of engineered strategies for interface regeneration. Many of the key mechanisms essential for interfacial tissue development and adaptation have high potential for improving outcomes in the clinic.