Binding and Release Characteristics of Insulin-Like Growth Factor-1 from a Collagen–Glycosaminoglycan Scaffold

Abstract

Tissue engineering is a promising technique for cartilage repair, but to optimize novel scaffolds before clinical trials, it is necessary to determine their characteristics for binding and release of growth factors. Toward this goal, a novel, porous collagen-glycosaminoglycan scaffold was loaded with a range of concentrations of insulinlike growth factor-1 (IGF-1) to evaluate its potential as a controlled delivery device. The kinetics of IGF-1 adsorption and release from the scaffold was demonstrated using radiolabeled IGF-1. Adsorption was rapid, and was approximately proportional to the loading concentration. Ionic bonding contributed to this interaction. IGF-1 release was studied over 14 days to compare the release profiles from different loading groups. Two distinct phases occurred: first, a burst release of up to 44% was noted within the first 24 h; then, a slow, sustained release (13%-16%) was observed from day 1 to 14. When the burst release was subtracted, the relative percentage of remaining IGF-1 released was similar for all loading groups and broadly followed t ½ kinetics until approximately day 6. Scaffold cross-linking using dehydrothermal treatment did not affect IGF-1 adsorption or release. Bioactivity of released IGF-1 was confirmed by seeding scaffolds (preadsorbed with unlabeled IGF-1) with human osteoarthritic chondrocytes and demonstrating increased proteoglycan production in vitro.

Release of growth factors from a reinforced collagen GAG matrix supplemented with platelet rich plasma: Influence on cultured human meniscal cells

“…27 Furthermore, PRP added to collagen matrix was able to increase the expression of collagen, elastin, and aggrecan genes which constitute key structural components of the menisci. This in vitro data suggests that there may be a small benefit to adding PRP to a minor meniscal defect where there is a possibility of the PRP to accumulate.…”

“…14,15,[22][23][24] Furthermore, collagen contains numerous biologically relevant binding motifs 22,25 and has been investigated for its ability to act as a local reservoir and mediator of biologically active materials such as IGF-1 or platelet rich plasma (PRP). 26,27 Collagen/glycosaminoglycan matrices have previously been used by us to examine uptake and delivery of IGF-1 over extended time periods to influence the growth and synthetic capabilities of human articular chondrocytes. 27 IGF-1, TGFb1, and PDGF have been demonstrated to influence meniscal fibroblasts by increasing expression of matrix proteins such as collagens and proteoglycans.…”

“…26,27 Collagen/glycosaminoglycan matrices have previously been used by us to examine uptake and delivery of IGF-1 over extended time periods to influence the growth and synthetic capabilities of human articular chondrocytes. 27 IGF-1, TGFb1, and PDGF have been demonstrated to influence meniscal fibroblasts by increasing expression of matrix proteins such as collagens and proteoglycans. 28,29 These and other growth factors can be concentrated from the blood with the production of PRP.…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…12,32-50 (3) Bioactive factors directly dispersed, immobilized, or adsorbed into the three-dimensional construct. 3,4,[6][7][8][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] The level of immobilization determines the release rate of GFs and consequently their effect on tissue formation. Several studies approach a particularly relevant immobilization method, mimicking native extracellular matrix (ECM), affinity-bound systems, through the inclusion of heparin domains on the structure, thus expecting an enhanced stability of the entrapped GF.…”

Numerical simulations to determine the influence of mould design on ice-templated scaffold structures

“…Producing collagen scaffolds by ice-templating has proven to be a very successful technique for tissue engineering, enabling cell culture to move from two-dimensional substrates towards three-dimensional scaffolds. They can be used for maintenance of cell phenotype in long term culture, creation of more effective drug delivery devices, and studies of whole tissue morphogenesis [6][7][8] .…”