Tunable Keratin Hydrogels for Controlled Erosion and Growth Factor Delivery

Abstract

Tunable erosion of polymeric materials is an important aspect of tissue engineering for reasons that include cell infiltration, controlled release of therapeutic agents, and ultimately to tissue healing. In general, the biological response to proteinaceous polymeric hydrogels is favorable (e.g., minimal inflammatory response). However, unlike synthetic polymers, achieving tunable erosion with natural materials is a challenge. Keratins are a class of intermediate filament proteins that can be obtained from several sources including human hair and have gained increasing levels of use in tissue engineering applications. An important characteristic of keratin proteins is the presence of a large number of cysteine residues. Two classes of keratins with different chemical properties can be obtained by varying the extraction techniques: (1) keratose by oxidative extraction and (2) kerateine by reductive extraction. Cysteine residues of keratose are “capped” by sulfonic acid and are unable to form covalent crosslinks upon hydration, whereas cysteine residues of kerateine remain as sulfhydryl groups and spontaneously form covalent disulfide crosslinks. Here, we describe a straightforward approach to fabricate keratin hydrogels with tunable rates of erosion by mixing keratose and kerateine. SEM imaging and mechanical testing of freeze-dried materials showed similar pore diameters and compressive moduli, respectively, for each keratose-kerateine mixture formulation (~1200 kPa for freeze-dried materials and ~1.5 kPa for hydrogels). However, the elastic modulus (G’) determined by rheology varied in proportion with the keratose-kerateine ratios, as did the rate of hydrogel erosion and the release rate of thiol from the hydrogels. The variation in keratose-kerateine ratios also led to tunable control over release rates of recombinant human insulin-like growth factor 1.

Enhanced performance of chitosan/keratin membranes with potential application in peripheral nerve repair

“…55 This is because keratin is a human-derived protein, and exhibits excellent biocompatibility, no immune reaction upon transplantation, good cellular interaction activity and biodegradability. 56 In this case, the aim was to provide new desirable and improved characteristics to CHT membranes. 16 Making use of the previously developed 5% DA CHT membrane, 16 which were found to be optimal for PNR, we intended to study of the effect related to the addition of 1% of freeze-dried hair keratin.…”

“…61 This is linked to the fact that keratin is a naturally hydrophilic protein. 56 The capacity to react with water is also visible in the weight loss and water uptake properties of the CHT/keratin membranes. In agreement with other reports, 62 the presence of keratin in the polymer blend makes it more prone to react with water molecules, achieving higher swelling and degradation rates due to hydrolysis.…”

Homo‐ and heteropolymer self‐assembly of recombinant trichocytic keratins

“…Collagen, elastin, silk, and keratin provide a few exquisite examples of functional biopolymers that have been implemented for materials design. Among these, keratin biopolymers have some of the most unique properties that make them especially well‐suited for the generation of biomaterials . First, as with silk and collagen proteins, keratin dimers can be reconstituted into functional materials following extraction from natural sources .…”

Carriers for the tunable release of therapeutics: etymological classification and examples

“…Also, micelles made of the block copolymer composed of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) and PLA-b-PNIPAm displayed a reduced release of ibuprofen as the content of PLA-b-PNIPAm increased [55]. Tuning the release as a function of the weight ratio between the two components of a carrier is often the consequence of their different affinity for the drug, and one example comes from the tunability of the release of recombinant human insulin-like growth factor 1 (rhIGF-1): with rhIGF-1 binding more intensely to more biodegradable kerateine (KTN) than to less biodegradable keratose (KOS), increasing the KTN/KOS weight ratio in a polymer increased the rate of release of rhIGF-1[56]. The release was tunable within the 10 – 70 % range after 7 days, as defined by the release from pure KTN (10 %) and pure KOS (70 %), respectively.…”

“…Tunability achievable in a system with a specific drug/carrier combination may be obliterated when the identity of the drug changes. One example comes from the aforementioned tunable release of rhIGF-1 from KOS/KTN polymer, impossible to repeat with another growth factor, recombinant human bone morphogenetic protein 2, or with an antibiotic, ciprofloxacin[56]. Finally, Table 2 lists some of the patented carriers with intrinsically tunable release properties.…”