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.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2010.0223

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

Gelatin as a delivery vehicle for the controlled release of bioactive molecules.

Polymer carriers for drug delivery in tissue engineering

Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin–hydroxyapatite for tissue engineering scaffolds

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.

Controlled growth factor delivery for tissue engineering.

Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation

The preparation of biodegradable hydrogel microspheres in the absence of surfactants was carried out by a two-step procedure which involved the formation of non-crosslinked microspheres from gelatin based on its inherent gelation nature at low temperatures and the subsequent glutaraldehyde (GA) crosslinking. The size of the microspheres was controlled in the range of 3 to 100 μm by changing the concentration of gelatin or GA, the emulsification method, and the crosslinking time. Neutral aqueous solutions of proteins with different isoelectric points (IEPs) and molecular weights (Mws) were infused into freeze-dried hydrogel microspheres to produce protein-incorporated gelatin microspheres. In vitro protein release from the microspheres depended on the protein's IEP but not on the Mw. The incorporated basic proteins with IEPs > 7.0 were released initially from the acidic gelatin microspheres, followed by no substantial release, whereas a larger initial release of the incorporated acidic proteins with IEPs <...

Surfactant-Free Preparation of Biodegradable Hydrogel Microspheres for Protein Release:

Electrocrystallization of the dicyanophthalocyaninatocobalt(III) anion, [Co(Pc)(CN)2]–, in a mixed solvent of acetonitrile and chloroform gives conducting neutral radical crystals of Co(Pc)(CN)2·2CHCl3. Similarly, that in a mixed solvent of acetonitrile or benzonitrile and water yields crystals of Co(Pc)(CN)2·2H2O. Since the molecule has two axial projections at the centre, a simple one-dimensional columnar structure cannot be formed. Instead, the crystal containing chloroform has two-dimensional sheets of phthalocyanines, and that containing water has a three-dimensional network of phthalocyanines. Their electrical resistivities are remarkably low as neutral radical crystals: that of Co(Pc)(CN)2·2H2O is the lowest of the π-based neutral radical crystals reported to date.

https://pubs.rsc.org/en/content/articlepdf/1995/jm/jm9950501749?page=search

Conducting neutral radical crystals of axially substituted phthalocyanine: crystal structures, dimensionality and electrical conductivity

Electrocrystallization of the dicyanophthalocyaninatocobalt(III) anion, [Co(Pc)(CN)2]−, gives three kinds of neutral radical crystals which are different in dimensionality. One-dimensional arrays of Co(Pc)(CN)2 are formed in the bromoform containing crystal, Co(Pc)(CN)2.2CHBr3. Two-dimensional sheets of Co(Pc)(CN)2 are formed in a crystal of Co(Pc)(CN)2.2CHCl3. A three-dimensional network of Co(Pc)(CN)2 is formed in Co(Pc)(CN)2.2H2O. The conductivity anisotropy is in good agreement with the dimensionality of the π-π interaction. The conductivity value, which is rather high as neutral radical solids, is systematically increased with increasing the dimensionality, suggesting that the conduction-limiting factor in a neutral radical system, on-site Coulomb repulsion energy, can be reduced by increasing the dimensionality.

Kazuhiro Morimoto

Papers

Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation

Surfactant-Free Preparation of Biodegradable Hydrogel Microspheres for Protein Release:

Conducting neutral radical crystals of axially substituted phthalocyanine: crystal structures, dimensionality and electrical conductivity

Molecular Conductors Based on Axially Substituted Phthalocyanine Neutral Radicals

Wide variety of dimensionality in phthalocyanine based molecular conductors