Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

Abstract

Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short half-lives in biological environments. Biomaterial-based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)-inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as cost-effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine.

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…For example, the protein functionalization which requires the specific active sequence of the biomolecules in the microenvironment can attract resident endogenous cells and allow them to adhere gradually to the surfaces, 173 indicating the critical importance of incorporating these biomolecules into the design of biomaterials and scaffolds for bone repair (Figure 18). Furthermore, sequestration of innate proteins such as growth factors by biomaterial‐based approaches is conducive to avoid the requirement of exogenous administration and has more potential in regenerative medicine 306 . In comparison to other publications resembling this review article, 14,31 we comprehensively summarize the material and design of bone‐mimicking scaffolds, their production techniques, and the current strategies for clinical bone repair, as well as techniques to facilitate bone regeneration through modification of the characteristics of scaffold materials.…”

Innovative Strategies in Tendon Tissue Engineering

“…Despite the over 1600 clinical trials registered con for the use of GFs, widespread regulatory approval and marketing are far from coming. Only a few, single GF-based formulations have been approved, by US-FDA (Food and Drug Administration) bone morphogenic protein (BMP)-2 and BMP-7 for lumbar spine fusion and bone fracture, platelet derived growth factor in BB isoform (PDGF)-BB for enhancement of granulation tissue formation and keratinocyte growth factor (KGF) for the prevention and treatment of mucositis in cancer patients; and by Japan and China, fibroblast growth factor (FGF)-2; and by Latin America and part of Asia, epidermal growth factor (EGF), all for wound healing [ 126 ].…”

Multifunctional Surfaces for Improving Soft Tissue Integration

“…The dynamic regulation of the sequestration, release, activation, and presentation to cell surface receptors of bioactive molecules is known to be highly relevant for its effective biological signaling, and functional materials recreating the ECM roles on these mechanisms have shown to drastically potential the effects of, for example, of growth factors. [37,38] Next, we investigated which specific PL proteins are sequestered by CNC surfaces ("hard" biomolecular corona). Using proteomic analysis, the number of proteins identified was 1033 (p < 0.05; ⩾2 unique peptides; in at least three replicates; full list of proteins available in Table S1, Supporting Information), which were then classified according to categories of biological process involved (Figure 3a).…”