Engineered bridge protein with dual affinity for bone morphogenetic protein-2 and collagen enhances bone regeneration for spinal fusion

Abstract

The revolutionizing efficacy of recombinant human bone morphogenetic protein (rhBMP-2) for clinical spinal fusion is hindered by safety issues associated with the high dose required. However, it continues to be widely used, for example, in InFUSE Bone Graft (Medtronic). Here, we developed a translational protein engineering–based approach to reduce the dose and thereby improve the safety of rhBMP-2 delivered in a collagen sponge, as in InFUSE Bone Graft. We engineered a bridge protein with high affinity for rhBMP-2 and collagen that can be simply added to the product’s formulation, demonstrating improved efficacy at low dose of rhBMP-2 in two mouse models of bone regeneration, including a newly developed spinal fusion model. Moreover, the bridge protein can control the retention of rhBMP-2 from endogenous collagenous extracellular matrix of tissue. Our approach may be generalizable to other growth factors and collagen-based materials, for use in many other applications in regenerative medicine.

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording

“…26,27 Considering the requirements of biocompatibility for long-term implantable applications, biologically-derived materials, such as alginate, collagen and gelatin, are more advantageous than synthetic polymers because of their superior biocompatibility, cell bioactivity and controllable degradation. [28][29][30] Among them, silk fibroin (SF) has raised increasing interest owing to its remarkable biocompatibility, tunable biodegradability, excellent optical transmittance, and controllable mechanical strength, and has been widely used as a fundamental component for the construction of wearable or implantable devices. [31][32][33] The limitations are the unstable mechanical properties of crosslinked SF hydrogels that occur due to stiffening over time under physiological conditions, which mostly result from the self-assembly of hydrophobic SF domains into large crystalline b-sheet structures, making it a challenge to develop SF hydrogels that exhibit the tissuemimicking mechanics of native tissues.…”

The Use of Collagen-Based Materials in Bone Tissue Engineering

“…For BTE, collagen sponges are mainly applied as basic scaffolds for carrying bioactive substances, including growth factors, cells, drugs, etc. Recently, a collagen sponge, combined with BMP-2 and a bridge protein, showed the improved safety of BMP-2 and effects on bone regeneration for spinal fusion [ 127 ]. A gene delivery system encoding fibroblast growth factor (FGF-2) and BMP-2 embedded in collagen sponge showed optimal bone regeneration effects [ 128 ].…”

Lipidation Alters the Structure and Hydration of Myristoylated Intrinsically Disordered Proteins

“…The development of new peptides/proteins has traditionally focused on engineering their amino acid sequence to regulate the structure–function for desired applications, including materials, − vaccines and biopharmaceuticals, − sensors, , and others. − In contrast, nature leverages posttranslational modifications (PTMs)the decoration of proteins with motifs such as phosphate, carbohydrates, and lipids, among othersto modulate protein structure, function, and location with exquisite spatiotemporal control . The chemical diversity of PTMs far surpasses the canonical design space of the 20–22 naturally occurring amino acids, exponentially increasing the diversity of proteinaceous molecules available to regulate the spatiotemporal flow of life-sustaining matter, energy, and information.…”