Controlled Growth Factor Delivery for Tissue Engineering

Abstract

Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular.

Liposomes in tissue engineering and regenerative medicine

“…Tissue regeneration depends not only on the bioactive agent itself such as growth factors (GFs), but also on the various parameters associated with its presentation, including concentration, spatio-temporal gradients, combination with other GFs and the target cell type [151][152][153][154]. Bioactive agent-loaded liposomes combined with scaffolds offer various intrinsic benefits such as: (i) effective concentration; (ii) stable concentration gradients; (iii) multiple bioactive agent delivery; and (iv) spatial patterning [27].…”

Photo-crosslinking hyaluronan-heparin hybrid hydrogels for BMP-2 sustained delivery

“…After glycidyl methacrylation, three new peaks appeared at ~1.85 ppm, ~5.6 ppm and ~6.1 ppm corresponding to H a , H b and H c in GMA, respectively, indicative of the successful incorporation of GMA into HA. Based on the relative integral intensity of H a , H b and H d , the GMA substitution degree was calculated to be 33% for HAGMA [8]. Similarly, for the spectrum of HPGMA (Figure 2), the new peaks at ~1.85 ppm, ~5.6 ppm and ~6.1 ppm were also observed, suggesting the successful linkage between GMA and HP.…”

“…In tissue engineering, the sustained delivery of GFs is usually necessary because of their in vivo short half-life and physicochemical instability [8]. Here, BMP-2 was used as the model GF for loading and delivery.…”

“…[4][5][6][7]. As a scaffold material for tissue regeneration, except the basic requirements on adequate mechanical property and good biocompatibility, the controlled release of growth factors (GFs) in favor of tissue regeneration is also necessary because of the in vivo short half-life of GFs [8]. However, because of lack of GFs binding domains in the HA molecules, the GFs controlled release of HA hydrogel still remains a challenge.…”

Polymeric multilayer capsules delivering biotherapeutics

“…[84] Successful administration of these proteins involves their delivery to the target site while maintaining biological activity and retention of the proteins in the tissue during a period in which their activity can be exerted. [83,85] Bolus injection of growth factors to the target site is generally not effective due to the short half-life of the growth factors and their fast diffusion from the injection site with concomitant toxicity in other tissues caused by non-specific distribution. [86] As a consequence controlling the release of the growth factor in terms of concentration and time span is an important issue.…”