Engineering growth factors for regenerative medicine applications

Aaron C. Mitchell, Priscilla S. Briquez, Jeffrey A. Hubbell, Jennifer R. Cochran

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications. Statement of significance Growth factors are promising therapeutic proteins that have the ability to modulate morphogenetic behaviors, including cell survival, proliferation, migration and differentiation. However, the translation of growth factors into clinical therapies has been hindered by properties such as poor protein stability, low recombinant expression yield, and non-physiological delivery, which lead to suboptimal efficacy and adverse side effects. To address these needs, researchers are employing clever molecular and material engineering and design strategies to both improve the intrinsic properties of growth factors and effectively control their delivery into tissue. This review highlights examples of interdisciplinary tools and technologies used to augment the therapeutic potential of growth factors for clinical applications in regenerative medicine.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalActa Biomaterialia
Volume30
DOIs
StatePublished - Jan 15 2016
Externally publishedYes

Fingerprint

Regenerative Medicine
Intercellular Signaling Peptides and Proteins
Proteins
Protein Stability
Tissue
Technology
Therapeutics
Protein Engineering
Cell proliferation
Cell Surface Receptors
Biocompatible Materials
Biomaterials
Extracellular Matrix
Half-Life
Cell Differentiation
Cell Survival
Repair
Research Personnel
Cell Proliferation

Keywords

  • Biomaterials
  • Controlled release
  • Drug delivery systems
  • Extracellular matrix
  • Growth factors
  • High-throughput screening
  • Mutagenesis
  • Protein engineering
  • Protein library
  • Regenerative medicine

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

Mitchell, A. C., Briquez, P. S., Hubbell, J. A., & Cochran, J. R. (2016). Engineering growth factors for regenerative medicine applications. Acta Biomaterialia, 30, 1-12. https://doi.org/10.1016/j.actbio.2015.11.007

Engineering growth factors for regenerative medicine applications. / Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

In: Acta Biomaterialia, Vol. 30, 15.01.2016, p. 1-12.

Research output: Contribution to journalArticle

Mitchell, Aaron C. ; Briquez, Priscilla S. ; Hubbell, Jeffrey A. ; Cochran, Jennifer R. / Engineering growth factors for regenerative medicine applications. In: Acta Biomaterialia. 2016 ; Vol. 30. pp. 1-12.
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