Biopolymeric delivery matrices for angiogenic growth factors

Andreas H. Zisch, Matthias P. Lutolf, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

The development of new therapeutic approaches that aim to help the body exert its natural mechanisms for vascularized tissue growth (therapeutic angiogenesis) has become one of the most active areas of tissue engineering. Through basic research, several growth factor families and cytokines that are capable to induce physiological blood vessel formation have been identified. Indeed, preclinical and clinical investigations have indicated that therapeutic administration of angiogenic factors, such as the prototypic vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), to sites of ischemia in the heart or the limb can improve regional blood flow. For new and lasting tissue vascularization, prolonged tissue exposure to these factors could be critical. Furthermore, as shown for VEGF, dosage must be tightly controlled, as excess amounts of VEGF can cause severe vascular leakage and hypotension. This review emphasizes natural and synthetic polymer matrices with respect to their development as vehicles for local and controlled delivery of angiogenic proteins, such as VEGF and bFGF, and their clinical applicability. In the dawn of experimental vascular engineering, new biomaterial schemes for clinical growth factor administration that take better account of biological principles of angiogenic growth factor function and the cell biological basis necessary to produce functional vasculature are evolving. Alongside their base function as protective embedment for angiogenic growth factors, these new classes of bioactive polymers are engineered with additional functionalities that better preserve growth factor activity and more closely mimic the in vivo release mechanisms and profiles of angiogenic growth factors from the extracellular matrix (ECM). Consequently, the preparation of both natural or completely synthetic materials with biological characteristics of the ECM has become central to many tissue engineering approaches that aim to deliver growth factors in a therapeutically efficient mode. Another promising venue to improve angiogenic performance is presented by biomaterials that allow sequential delivery of growth factors with complementary roles in blood vessel initiation and stabilization.

Original languageEnglish
Pages (from-to)295-310
Number of pages16
JournalCardiovascular Pathology
Volume12
Issue number6
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Fingerprint

Angiogenesis Inducing Agents
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
Blood Vessels
Biocompatible Materials
Fibroblast Growth Factor 2
Tissue Engineering
Extracellular Matrix
Polymers
Angiogenic Proteins
Regional Blood Flow
Hypotension
Therapeutics
Ischemia
Extremities
Cytokines
Growth
Research

Keywords

  • Cell-responsive matrix
  • Controlled release
  • Growth factor
  • Natural biopolymers
  • Synthetic biopolymers
  • Therapeutic angiogenesis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pathology and Forensic Medicine

Cite this

Biopolymeric delivery matrices for angiogenic growth factors. / Zisch, Andreas H.; Lutolf, Matthias P.; Hubbell, Jeffrey A.

In: Cardiovascular Pathology, Vol. 12, No. 6, 01.11.2003, p. 295-310.

Research output: Contribution to journalArticle

Zisch, Andreas H. ; Lutolf, Matthias P. ; Hubbell, Jeffrey A. / Biopolymeric delivery matrices for angiogenic growth factors. In: Cardiovascular Pathology. 2003 ; Vol. 12, No. 6. pp. 295-310.
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