Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Abstract

The identification and production of recombinant morphogens and growth factors that play key roles in tissue regeneration have generated much enthusiasm and numerous clinical trials, but the results of many of these trials have been largely disappointing. Interestingly, the trials that have shown benefit all contain a common denominator, the presence of a material carrier, suggesting strongly that spatio-temporal control over the location and bioactivity of factors after introduction into the body is crucial to achieve tangible therapeutic effect. Sophisticated materials systems that regulate the biological presentation of growth factors represent an attractive new generation of therapeutic agents for the treatment of a wide variety of diseases. This review provides an overview of growth factor delivery in tissue engineering. Certain fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives are discussed. Recent progress highlights the importance of materials science and engineering in growth factor delivery approaches to regenerative medicine.

Design Advances in Particulate Systems for Biomedical Applications

“…Growth factors and cytokines act integrated with other biomolecules within a timing period and in a specifi c cell phenotype. [ 8 ] In general, orchestrated interactions are involved, determining a complex sequence of cell migration, proliferation, differentiation and protein synthesis. Skin wound healing, [ 9 ] bone repair, [ 10,11 ] and reestablishment of vascularized networks [ 12 ] are examples of natural processes highly dependent on the coordinated activity of released biomolecules and the activity of different cell types.…”

“…Drug release systems capable to sustain the plasma concentration of natural bioactive agents or mimic the local signalling are being widely explored. Recombinant growth factors [ 8 ] or even cocktails of these kind of proteins obtained from the platelets existent in the blood plasma (platelet lysates) [ 13,14 ] have been applied as bioactive agents for regeneration of several tissues. Vascular endothelial growth factor has been used to promote angiogenesis and for ischemia treatment; [ 15,16 ] bone morphogenic proteins for bone regeneration; [ 17,18 ] epidermal growth factor for treatment of skin lesions resultant from burns or chronic ulcers; [ 19 ] glial cell-line neurotrophic factor for spinal cord injuries or peripheral nerves regeneration; [ 20 ] and IL-10 for treatment of infl ammatory bowel disease and to suppress infl ammation.…”

Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration

“…Additionally, excess amounts of rhVEGF can actually inhibit osteogenesis, associating with severe vascular leakage and hypotension 22. Therefore, the amount and timing of rhBMP‐2 and rhVEGF delivery is critical to enhance bone formation and localized vascularization simultaneously 20, 23. The smart nanocoating used in our design can not only be utilized to immobilize bioactive components onto biomaterial surfaces, but also to control the growth factors quantity and sequential release.…”

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

“…38 Here, we highlight advances using naturally derived polymers in hydrogel formation, such as fibrin and alginate. Fibrin is a naturally derived and US FDA-approved biomaterial that is commercially available 28 and has been extensively used for a variety of therapeutic applications.…”