Rational Design of High‐Performance Keratin‐Based Hemostatic Agents

Abstract

Keratins are considered ideal candidates as hemostatic agents, but the development lags far behind their potentials due to the poorly understood hemostatic mechanism and structure-function relations, owing to the composition complexity in protein extracts. Here, it is shown that by using a recombinant synthesis approach, individual types of keratins can be expressed and used for mechanism investigation and further high-performance keratin hemostatic agent design. In the comparative evaluation of full-length, rod-domain, and helical segment keratins, the 𝜶-helical contents in the sequences are identified to be directly proportional to keratins' hemostatic activities, and Tyr, Phe, and Gln residues at the N-termini of 𝜶-helices in keratins are crucial in fibrinopeptide release and fibrin polymerization. A feasible route to significantly enhance the hemostatic efficiency of helical keratins by mutating Cys to Ser in the sequences for enhanced water wettability through soluble expression is then further presented. These results provide a rational strategy to design high-efficiency keratin hemostatic agents with superior performance over clinically used gelatin sponge in multiple animal models.

Individual Human Hair Keratin Rapidly Extracted Through the Advanced Oxidation Process and Their Hemostatic and Wound Healing Evaluations

“…Hemostasis is the earliest application of keratin biomaterials, which was traced back to the 16th century. 13 We assumed that there was a difference in the hemostasis effect for the individual keratins. Therefore, we extracted four individual keratins (HK1, HK2, HK3, and HK4) using the H 2 O 2 /UV/TiO 2 method, and the individual keratin coating on PCL nanofibrous substrates was prepared using a physical deposition method (Figure 4a).…”

“…The keratins with different concentrations ranging from 1 mg/mL were coated on PCL nanofibrous substrates, which was prepared using a physical deposition method. 13 PCL nanofibers were put on a glass dish, and the keratin protein after the ultrafiltration process was dipped onto the surface of nanofiber. The keratin/PCL nanofibers were incubated at 37 °C for 2 h at 50 rpm until the dry nanofibers were obtained.…”

Recent advances in biopolymer-based hemostatic materials

“…In addition, they cause polymerization of fibrinogen into fibrin which also contributes to hemostasis. In a comparative study by Wang et al [ 127 ], they observed that the α-helical segment contents of keratin are directionally proportional to its hemostatic activity, while the Tyr, Phe and Gln amino acids at the N-termini of the α-helices in keratins play an important role in fibrin polymerization. He et al [ 128 ] fabricated keratin-based hydrogels extracted from human hair, named K-gels ( Fig.…”

Design of biopolymer-based hemostatic material: Starting from molecular structures and forms

“…Moreover, some have pointed out that, as biogenic polypeptides, it is difficult to control the keratin's amino acid composition, batch-to-batch difference, and complex keratin-related proteins. These have stalled the exploration of its use for hemostasis [ 103 ]. Synthesis of recombinant keratin through bioengineering methods may ultimately solve the above problems.…”