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Keratin (KRT), a natural fibrous structural protein, can be classified into two categories: "soft" cytosolic KRT that is primarily found in the epithelia tissues (e.g., skin, the inner lining of digestive tract) and "hard" KRT that is mainly found in the protective tissues (e.g., hair, horn). The latter is the predominant form of KRT widely used in biomedical research. The oxidized form of extracted KRT is exclusively denoted as keratose (KOS) while the reduced form of KRT is termed as kerateine (KRTN). KOS can be processed into various forms (e.g., hydrogel, films, fibers, and coatings) for different biomedical applications. KRT/KOS offers numerous advantages over other types of biomaterials, such as bioactivity, biocompatibility, degradability, immune/inflammatory privileges, mechanical resilience, chemical manipulability, and easy accessibility. As a result, KRT/KOS has attracted considerable attention and led to a large number of publications associated with this biomaterial over the past few decades; however, most (if not all) of the published review articles focus on KRT regarding its molecular structure, biochemical/biophysical properties, bioactivity, biocompatibility, drug/cell delivery, and in vivo transplantation, as well as its applications in biotechnical products and medical devices. Current progress that is directly associated with KOS applications in tissue regeneration and drug delivery appears an important topic that merits a commentary. To this end, the present review aims to summarize the current progress of KOS-associated biomedical applications, especially focusing on the in vitro and in vivo effects of KOS hydrogel on cultured cells and tissue regeneration following skin injury, skeletal muscle loss, peripheral nerve injury, and cardiac infarction. [ABSTRACT FROM AUTHOR]

Objective To determine whether the addition of kerateine (reduced keratin) in rat tail collagen type I hydrogels increases thermal stability and changes material properties and supports cell growth for use in cellular hyperthermia studies for tumor treatment. Methods Collagen type I extracted from rat tail tendon was combined with kerateine extracted from human hair fibers. Thermal, mechanical, and biocompatibility properties and cell behavior was assessed and compared to 100% collagen type I hydrogels to demonstrate their utility as a tissue model for 3D in vitro testing. Results A combination (i.e., containing both collagen ‘C/KNT’) hydrogel was more thermally stable than pure collagen hydrogels and resisted thermal degradation when incubated at a hyperthermic temperature of 47°C for heating durations up to 60 min with a higher melting temperature measured by DSC. An increase in the storage modulus was only observed with an increased collagen concentration rather than an increased KTN concentration; however, a change in ECM structure was observed with greater fiber alignment and width with an increase in KTN concentration. The C/KTN hydrogels, specifically 50/50 C/KTN hydrogels, also supported the growth and of fibroblasts and MDA-MB-231 breast cancer cells similar to those seeded in 100% collagen hydrogels. Conclusion This multi-protein C/KTN hydrogel shows promise for future studies involving thermal stress studies without compromising the 3D ECM environment or cell growth.

Age-related macular degeneration (AMD) is a retinal disease that affects 196 million people and causes nearly 9% of blindness worldwide. While several pharmacological approaches slow the effects of AMD, in our opinion, cell-based strategies offer the most likely path to a cure. We describe the design and initial characterization of a kerateine (obtained by reductive extraction from keratin proteins) aerogel-electrospun polycaprolactone fiber scaffold system. The scaffolds mimic key features of the choroid and the Bruch's membrane, which is the basement membrane to which the cells of the retinal pigment epithelium (RPE) attach. The scaffolds had elastic moduli of 2–7.2 MPa, a similar range as native choroid and Bruch's membrane. ARPE-19 cells attached to the polycaprolactone fibers, remained viable for one week, and proliferated to form a monolayer reminiscent of that needed for retinal repair. These constructs could serve as a model system for testing cell and/or drug treatment strategies or directing ex vivo retinal tissue formation in the treatment of AMD. [ABSTRACT FROM AUTHOR]

To determine whether the addition of kerateine (reduced keratin) in rat tail collagen type I hydrogels increases thermal stability and changes material properties and supports cell growth for use in cellular hyperthermia studies for tumor treatment. Collagen type I extracted from rat tail tendon was combined with kerateine extracted from human hair fibers. Thermal, mechanical, and biocompatibility properties and cell behavior was assessed and compared to 100% collagen type I hydrogels to demonstrate their utility as a tissue model for 3D in vitro testing. A combination (i.e., containing both collagen ‘C/KNT’) hydrogel was more thermally stable than pure collagen hydrogels and resisted thermal degradation when incubated at a hyperthermic temperature of 47°C for heating durations up to 60 min with a higher melting temperature measured by DSC. An increase in the storage modulus was only observed with an increased collagen concentration rather than an increased KTN concentration; however, a change in ECM structure was observed with greater fiber alignment and width with an increase in KTN concentration. The C/KTN hydrogels, specifically 50/50 C/KTN hydrogels, also supported the growth and of fibroblasts and MDA-MB-231 breast cancer cells similar to those seeded in 100% collagen hydrogels. This multi-protein C/KTN hydrogel shows promise for future studies involving thermal stress studies without compromising the 3D ECM environment or cell growth. [ABSTRACT FROM AUTHOR]

Abstract Background Nanotechnology-based drug delivery systems have been widely used for oral and systemic dosage forms delivery depending on the mucoadhesive interaction, and keratin has been applied for biomedical applications and drug delivery. However, few reports have focused on the keratin-based mucoadhesive drug delivery system and their mechanisms of mucoadhesion. Thus, the mucoadhesion controlled kerateine (reduced keratin, KTN)/keratose (oxidized keratin, KOS) composite nanoparticles were prepared via adjusting the proportion of KTN and KOS to achieve controlled gastric mucoadhesion and drug release based on their different mucoadhesive abilities and pH-sensitive properties. Furthermore, the mechanisms of mucoadhesion for KTN and KOS were also investigated in the present study. Results The composite keratin nanoparticles (KNPs) with different mass ratio of KTN to KOS, including 100/0 (KNP-1), 75/25 (KNP-2), 50/50 (KNP-3), and 25/75 (KNP-4), displayed different drug release rates and gastric mucoadhesion capacities, and then altered the drug pharmacokinetic performances. The stronger mucoadhesive ability of nanoparticle could supply longer gastric retention time, indicating that KTN displayed a stronger mucoadhesion than that of KOS. Furthermore, the mechanisms of mucoadhesion for KTN and KOS at different pH conditions were also investigated. The binding between KTN and porcine gastric mucin (PGM) is dominated by electrostatic attractions and hydrogen bondings at pH 4.5, and disulfide bonds also plays a key role in the interaction at pH 7.4. While, the main mechanisms of KOS and PGM interactions are hydrogen bondings and hydrophobic interactions in pH 7.4 condition and were hydrogen bondings at pH 4.5. Conclusions The resulting knowledge offer an efficient strategy to control the gastric mucoadhesion and drug release of nano drug delivery systems, and the elaboration of mucoadhesive mechanism of keratins will enable the rational design of nanocarriers for specific mucoadhesive drug delivery.

In this work, two forms of keratins, kerateine (KR) and keratose (KO), were fabricated respectively into electrospun nanofibers by combination with polyurethane (PU). The differences of the structure and material properties between KR and KO based fibers were investigated by SEM observation, ATR-FTIR, XRD, contact angle, tensile test, in vitro degradation and cytocompatibility assay. The results indicated that the KR based nanofibers exhibited a higher tensile modulus, lower fracture strain and slower degradation rate, mainly due to the reformation of disulfide crosslinking between the regenerated cysteines in KR after the reductive extraction. The KO based nanofibers demonstrated a stronger hydrophilic property and higher water uptake ability due to the cysteic acid residues resulting from the oxidative extraction. Furthermore, the combination of keratins, regardless of KR or KO, could obviously improve the cytocompatibility of PU, especially in the cell attachment stage. [ABSTRACT FROM AUTHOR]

Uncontrolled bleeding frequently occurs in some emergencies which can result in severe injury and even death. Keratin hydrogel has been found that it had good ahemostatic efficacy in the previous studies. However, an ideal hemostatic agent should not require mixing or preparation in advance, and hydrogel is not easy to store and carry. In the present study, the kerateine was firstly extracted from human hair, and then was prepared nanoparticles by a modified emulsion diffusion method. The synthesized nanoparticles showed spherical morphology with an average diameter of approximately 200 nm. The results of Fourier transform infrared spectroscopy and X-ray diffraction indicated that the chemical structure of kerateine did not change but the crystal form may be transformed in the nanoparticles. In addition, kerateine nanoparticles displayed a faster clotting time in vitro study than the kerateine extracts. Furthermore, kerateine nanoparticles significantly reduced the blood loss and coagulation time in the liver puncture and tail amputation in rat models. Our results indicated that kerateine nanoparticles could quickly form a high viscosity gel onto the wound and accelerate the blood coagulation based on their high specific surface area. Therefore, kerateine nanoparticles have great potential for hemostatic application. [ABSTRACT FROM AUTHOR]

Surface characterization of materials has been considered critical in the development of biomaterials, as many unfavorable responses from the body occur at the interface between a material and the body component. The contact angle measurement is one means to characterize the surface properties and to correlate them to the biocompatibility of materials. In this paper, surface characteristics of silk fibroin/S-carboxymethyl kerateine, representative fibrous proteins, were investigated by contact angle measurements and ESCA. The biocompatibility of the blends was evaluated based on minimal interfacial free energy concept, and compared with other potential biomaterials. It was also hypothesized that the enhanced surface polarity of the blends was generated from the conformational transition of proteins. This approach to evaluate the biocompatibility of materials based on surface characteristics may find wide utility in many biomedical applications. [ABSTRACT FROM AUTHOR]

Molecular-weight measurements made on solutions of wool proteins that were not separated into high- and low-sulphur fractions are first reviewed. All the published studies of the molecular weights of the low-sulphur group of wool proteins are then critically discussed, in chronological order, from the standpoint of present knowledge. The relationships between the various protein fractions resulting from different methods of extraction arc outlined, and the applicability of the different methods used for measuring their molecular weights and the interpretation of the results obtained with them are considered in some detail, especially with respect to molecular-weight heterogeneity. By such discussion, it is attempted throughout the review to give reasons for thinking which results still have significance towards understanding the rôle of the low-sulphur proteins in the structure of wool and which may now be regarded as of historical interest only. Finally, current knowledge of the molecular weights of the low-sulphur wool proteins is summarized, and aspects of their solution behaviour that still need investigation are indicated. [ABSTRACT FROM AUTHOR]

An account is given of an investigation of the influence of dry heat on wool keratin. It is shown by three different chemical techniques that cross-linking occurs up to a temperature at which the amino-acid decomposition becomes marked. Although Iysinoalanine and lanthionine are shown to be formed, these amino acids do not appear to be major contributors to the cross-linking of the heated protein. The covalent binding of the e-amino group of lysine was determined quantitatively, and, from the results obtained, it is deduced that this group is involved to a large extent in the formation of cross-links. On the basis of these findings, it is postulated that amide cross-links are formed through the ε-amino group of lysine by reaction with carboxylic side chains of aspartic or glutamic acids or their amide derivatives. [ABSTRACT FROM AUTHOR]

Impact Statement: Recombinant human bone morphogenetic protein 2 (rhBMP-2) delivery from collagen sponges for bone formation is an important clinical example of growth factors in tissue engineering. Side effects from rhBMP-2 burst release and rapid collagen resorption have led to investigation of alternative carriers. Here, keratin carriers with tunable erosion rates were formulated by varying disulfide crosslinking via ratios of oxidatively (keratose) to reductively (kerateine) extracted keratin. In vitro rhBMP-2 bioactivity increased with kerateine content, reaching levels greater than with collagen. Heterotopic bone formation in a mouse model depended on the keratin formulation, highlighting the importance of the growth factor carrier.