Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration

Charlotte H Chen; Erin L Hsu; Samuel I Stupp

doi:10.1016/j.bone.2020.115565

Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration

Bone. 2020 Dec:141:115565. doi: 10.1016/j.bone.2020.115565. Epub 2020 Jul 31.

Authors

Charlotte H Chen¹, Erin L Hsu², Samuel I Stupp³

Affiliations

¹ Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA; Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA.
² Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA; Department of Orthopaedic Surgery, Northwestern University, 676 North St. Clair Street, Chicago, IL 60611, USA.
³ Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA; Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA; Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA; Department of Medicine, Northwestern University, 676 North St. Clair Street, Chicago, IL 60611, USA. Electronic address: s-stupp@northwestern.edu.

Abstract

Recombinant human bone morphogenetic proteins (BMPs) have shown clinical success in promoting bone healing, but they are also associated with unwanted side effects. The development of improved BMP carriers that can retain BMP at the defect site and maximize its efficacy would decrease the therapeutic BMP dose and thus improve its safety profile. In this review, we discuss the advantages of using self-assembling peptides, a class of synthetic supramolecular biomaterials, to deliver recombinant BMPs. Peptide amphiphiles (PAs) are a broad class of self-assembling peptides, and the use of PAs for BMP delivery and bone regeneration has been explored extensively over the past decade. Like many self-assembling peptide systems, PAs can be designed to form nanofibrous supramolecular biomaterials in which molecules are held together by non-covalent bonds. Chemical and biological functionality can be added to PA nanofibers, through conjugation of chemical moieties or biological epitopes to PA molecules. For example, PA nanofibers have been designed to bind heparan sulfate, a natural polysaccharide that is known to bind BMPs and potentiate their signal. Alternatively, PA nanofibers have been designed to synthetically mimic the structure and function of heparan sulfate, or to directly bind BMP specifically. In small animal models, these bio-inspired PA materials have shown the capacity to promote bone regeneration using BMP at doses 10-100 times lower than established therapeutic doses. These promising results have motivated further evaluation of PAs in large animal models, where their safety and efficacy must be established before clinical translation. We conclude with a discussion on the possiblity of combining PAs with other materials used in orthopaedic surgery to maximize their utility for clinical translation.

Keywords: BMP-2 delivery; Biomaterials; Self-assembling peptides; Supramolecular biomaterials; Synthetic biomaterials.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biocompatible Materials
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / administration & dosage*
Bone Regeneration
Drug Delivery Systems*
Humans
Nanofibers*
Peptides*

Substances

Biocompatible Materials
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding