Immobilization of Growth Factors for Cell Therapy Manufacturing

Abstract

Cell therapy products exhibit great therapeutic potential but come with a deterring price tag partly caused by their costly manufacturing processes. The development of strategies that lead to cost-effective cell production is key to expand the reach of cell therapies. Growth factors are critical culture media components required for the maintenance and differentiation of cells in culture and are widely employed in cell therapy manufacturing. However, they are expensive, and their common use in soluble form is often associated with decreased stability and bioactivity. Immobilization has emerged as a possible strategy to optimize growth factor use in cell culture. To date, several immobilization techniques have been reported for attaching growth factors onto a variety of biomaterials, but these have been focused on tissue engineering. This review briefly summarizes the current landscape of cell therapy manufacturing, before describing the types of chemistry that can be used to immobilize growth factors for cell culture. Emphasis is placed to identify strategies that could reduce growth factor usage and enhance bioactivity. Finally, we describe a case study for stem cell factor.

Advances in Growth Factor Delivery for Bone Tissue Engineering

“…Different techniques are available to entrap drug molecules in the structure of scaffolds, which facilitate their contact with migrating cells and regulate cell behavior ( Figure 7 ). Surface presentation entitles site-specific drug delivery and could narrow their potential off-target side effects [ 117 ]. The two key methods for introducing biomolecules to the scaffold surface are physical adsorption and chemical conjugation.…”

“…From a technical point of view, physical adsorption can be considered the most straightforward method for embedding biomolecules into polymer scaffolds [ 117 ]. Physical adsorption can be obtained by integrating biomolecules into a polymer matrix before its gelatinization [ 122 ] or by immersing the preformed scaffold in a protein solution.…”

“…Thus, GF retention relies on its appropriate immobilization on or absorption into the substrate [ 124 ]. Surface characteristics such as wettability, roughness, surface functionalities, charge density, and surface charge are some material properties that can affect the physical adsorption of biomolecules on the surface of polymer scaffolds [ 117 ]. Physical immobilization of GFs is an easy to accomplish technique in mild conditions and, thus, has raised much interest.…”

Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies

“…Instead of rapidly degradable growth factors, gene therapies have been recently investigated to immobilize viral vectors on polymeric scaffold surfaces for alveolar bone tissue formation [ 173 , 174 , 175 ]. In particular, the chemical vapor deposition (CVD) technique can modify FDA-approved biopolymeric material surfaces with chemical conjugations of antibodies, which mediate in the immobilization of viral vectors on the scaffold surfaces [ 169 , 173 , 174 , 176 ]. Hao et al treated three different biomaterial surfaces using the CVD technique to immobilize adenoviral vectors of PDGF-BB (AdPDGF-BB) and BMP-7 (AdBMP-7) for spatially compartmentalized tissue formations [ 174 ].…”

Self‐Assembly and Mechanical Properties of Engineered Protein Based Multifunctional Nanofiber for Accelerated Wound Healing

“…Angiogenesis is one of the significant events that regulates and promotes wound healing. [5] There are not many materials except hydrogels made up of modified collagen, [6][7][8] elastin, [9,10] gelatin, [11,12] and fibrin, [13,14] selfassembled short oligopeptides [15,16] and synthetic polymers immobilized with growth factors promoting angiogenesis [17,18] that has been reported thus far, and it remains a challenge to develop biomaterials with manipulation of protein parameters. Biomaterials that induce angiogenic growth factors to restore the reduced capillary density for improving naturally deteriorated microcirculation in ischemic and normoxic tissue would be an ideal choice for wound dressing.…”