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bioRxiv · 10.1101/2024.04.29.591537

Biocompatibility of KAPs-Depleted Residual Hair

Meer, A.·Mathews, A.·Cabral, M.·Tarabokija, A.·Carroll, E.·Chaudhry, H.·Paszek, M.·Radecker, N.·Palaia, T.·de Guzman, R. C.
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Abstract

This work is an in-depth investigation of the in vitro and in vivo biocompatibility of processed and treated residual human hair samples with intact cuticle layers. The specimens included oxidized hair with no melanin (BLH) and hair with medium-(M-KAP) and low-(L-KAP) levels of keratin associated proteins (KAPs), confirmed through gel electrophoresis, electron microscopy, and trichrome histological staining, in comparison to the untreated regular hair (REG) control. All hair groups, high KAPs (H-KAPs: REG and BLH), M-KAP, and L-KAP, were found to be non-cytotoxic in the adipose fibroblast cell lines response to their extracts based on the ISO 10993-5 medical device biomaterial testing standard. In vivo mouse subcutaneous implantation (ISO 10993-6, local effects) at 2 weeks showed that the samples caused a foreign body response (FBR) with a thin fibrous encapsulation at a mean value of 28% relative skin dermis thickness; but notably, the L-KAP implant mitigated a statistically significant decrease in FBR area compared to H-KAPs (REG and/or BLH) and a lower number of cells, including immune cells of mostly macrophages and mast cells on the biomaterials surface, normalized to implant and tissue coverage. In the bulk of the capsules, blood vessels and collagen extracellular matrix densities were similar among groups. These findings suggest that small globular KAPs diffuse out of the cortex to the host-biomaterial interface which induce a slightly elevated FBR but limited to the implants surface vicinity. On-going follow-up research focuses on purer keratin-based macromolecularly organized residual hair biomaterials, those with depleted KAPs, for drug-delivery gel implants as they are deemed the most biocompatible. Statement of SignificanceHuman hair is an abundant biological product that is regularly discarded and wasted but has the potential to be a clinical implantable allograft biomaterial. There are currently just two FDA class II-510(k)-approved medical devices from hair, limited to surface / skin wound care use, and no class III-PMA or biologics-BLA implants. Also, these products and those in research and development phases are based on soluble keratin and KAPs extracts utilizing tedious processing conditions and requiring oxidation reaction for reassembly into gels and scaffolds. Here we describe that the insoluble residual hair biomaterials with organized keratin structure, higher-degree of disulfide crosslinks, and particularly those with depleted KAPs have increased biocompatibility based on pre-clinical ISO 10993 standards. This novel natural biomaterials are now being developed as drug-delivery implantable gels for clinical applications.

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Meer, A., Mathews, A., Cabral, M., Tarabokija, A., Carroll, E., Chaudhry, H., Paszek, M., Radecker, N., Palaia, T., de Guzman, R. C.. 2024-05-01. Biocompatibility of KAPs-Depleted Residual Hair. https://doi.org/10.1101/2024.04.29.591537

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