Table 2 Wound healing applications of keratin and keratin-based biomaterials

PVA and Keratin

Sheep Wool

Asymmetric Nanofibers-Membranes

Top layer is made up of cross-linked PVA nanofibers and bottom layer is composed of wool keratins and PVA. Keratin/PVA asymmetric membranes displayed improved cell adhesion in in vitro experiments.

[102]

Silk-wool-Tannic acid

Sheep Wool

Hydrogel

These hydrogels possessed porous structure that could support cell growth and proliferation. The hydrogel demonstrates in situ gelation, recyclability, moldability, elasticity (G’>100 kPa), adhesiveness, self-healing properties, 3D printability, antibacterial activity, antioxidant properties, and biocompatibility.

[48]

Bacterial cellulose and keratin

Human hair

Scaffolds

The scaffolds do not show any toxicity to cells under cytocompatibility tests. These scaffolds were grafted on dorsal region of rabbit over a burned wound and displayed the potential of regeneration at the wound site.

[91]

Keratin-derived powder containing silver nanoparticles

Mouse fur

Wound dressing

These keratin dressings were found to be biocompatible in diabetic mice model, it increased the rate of wound closure and epithelization after a period of 5 and 8 days. The wounds treated with these dressings mostly showed the presence of macrophages whereas the untreated mice wounds were had a greater number of neutrophiles. Presence of macrophages favours healing and tissue regeneration.

[57]

Keratin fibres supplemented with 0.1% sodium butyrate

Rat fur

Wound dressing

These dressings have heterogenous structure and the butyrate was released slowly into the wounds. These dressings are non-toxic and promotes proliferation of cells in diabetic rats. The treated wounds also showed increased mRNA expression of keratin 16 and 17.

[59]

Reduced keratin, hyperbranched polymer and MnO2 nanoparticles

Human hair

Composite hydrogel

These hydrogels displayed antibacterial properties against gram positive and gram-negative bacteria. The composite hydrogel also scavenged ROS and protected L929 cells from oxidative stress.

[67]

Keratose (KO) and Kerateine (KN)

Human hair

LL-37 encapsulated hydrogel dressings

Sustained release of LL-37 from the keratin hydrogel was obtained by these hydrogels that resulted in improved wound healing by increase in fibroblast proliferation in full thickness rat wounds. Enhanced cell adhesion and migration was also reported. L-KO25:KN75 is capable of eradicating both Gram-negative and Gram-positive bacteria after 18 h. mRNA expression of VEGF (Vascular endothelial growth factor) and IL-6 (Interleukin-6) was also enhanced in treated groups.

[50]

Poly(L-lactate-caprolactone) copolymer (PLCL) and keratin

Human hair

Bilayer hydrogel wound dressing loaded with fibroblast growth factor (FGF-2)

This material possessed good porosity with water absorption of 874.09%. Elastic modulus - about 44kPa. Biocompatible and Biodegradable. In vivo - promoted re-epithelialization, collagen deposition, skin appendages (hair follicles) regeneration, micro angiogenesis construction, and adipose-derived stem cells (ADSCs) recruitment

[151]

Keratin and biphalin

Mouse fur

ber-dressing

These dressings increased proliferation in NIH/3T3 cell lines. Slow biphalin release from the dressing onto wound in experimental diabetic mice resulted in increasing expression level of mTOR, and p-AKT 72 at 72h. Acceleration in would healing is reported on days 5 and 15.

[99]

Keratin

Human Hair

Keratin Matrices

Degradation resistant, contained more than 99% keratin. Human epidermal keratinocytes grown in contact with these matrices showed increased expression of epidermal growth factor. Also, increased of cytokines was observed in these cells.

[93]

Keratin

Sheep Wool

Hydrolysates

These hydrolysates possess favourable cytotoxicity profile and displays anti - inflammatory properties in endothelial cells.

[83]

Keratin

Human hair

Hydrogel loaded with Human Platelet Lysate

Hydrogel formed with 15% keratin were stable and supported cell growth without cytotoxicity for 3 days under in vitro conditions

[153]

Keratin and casomorphin

Mouse fur

Wound Dressing

Wounds showed reepithelization quicker with these dressings. The dressing stimulated macrophages infiltration, which favours tissue remodelling and regeneration.

[58]

Keratin

Human hair

Ulcer-adhesive Hydrogel

These hydrogels increased the rate of ethanol-induced gastric ulcer healing by stopping the bleeding, preventing the epithelium cells from gastric acid damage, suppressing inflammation and promoting re-epithelization in rat .

[18]

Keratin

Human hair

Hydrogel

Keratin hydrogels treated irradiated wounds showed an increased rate of closure in comparison to untreated group in rats.

[16]

S-nitrosated keratin and polyurethane

Human hair

biocomposite mats/ dressings

The bio composite mats released NO for 72 hrs and possessed cytocompatibility and antibacterial activity. These mats promoted wound healing.

[26]

Keratin and PVA

Human hair

Scaffolds

The scaffolds loaded gentamycin sulphate (GS) as a model drug were prepared with Keratin and PVA by using alginate dialdehyde as crosslinking agent. These scaffolds promoted wound healing and demonstrated biocompatibility with NIH 3T3 fibroblast cells.

[79]

Keratin, cysteine and glucose oxidase (GOD)

Chicken feather

Hydrogel

GOD catalysed oxidation shortened the gelation time to almost 3 mins in a full thickness wound bed in in mice and improved the mechanical strength of the keratin hydrogel. Deferoxamine-loaded hydrogels also accelerated the wound healing in diabetic rats.

[17]

Polyacrylonitrile (PAN) and Keratin

Chicken feathers

Nanofiber mats

The electrospun PAN/Keratin mats had smooth surface and increased porosity with 0.05% keratin concentration. The mats demonstrated antibacterial properties against Pseudomonas aeruginosa and Staphylococcus aureus.

[108]

Sulfobetaine and Keratin

Human Hair

Hydrogel Dressing

Chlorhexidine (CHX) loaded hydrogels displayed cytocompatibility, antioxidant property as well as antibacterial activity. The CHX was released in wound microenvironments.

[109]

Keratin, Sodium Alginate and zinc oxide nanoparticles (ZnO NPs)

Goat hoof

Wound dressing

Zinc oxide nanoparticles (ZnO NPs) using C. roseus (leaf part) imparts good antibacterial activity, increases swelling of the dressing mats. These mats exhibited biocompatibility with NIH 3T3 fibroblast cells with accelerated wound healing.

[106]

Keratin

Human hair

Human keratin matrices (HKM)

HKM were composed of greater than 99% human keratin (Fig.2). Adult human epidermal keratinocytes (HEKa) cultured in contact with HKM depicted enhanced expression of Epidermal Growth Factor (EGF) and increased release of cytokines. In vivo studies in mice suggested accelerated wound closure with HKM in comparison to amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS)

[93]