Self-assembling peptide scaffolds in the clinic

Abstract

Well-defined scaffold hydrogels made of self-assembling peptides have found their way into clinical products. By examining the properties and applications of two self-assembling peptides-EAK16 and RADA16-we highlight the potential for translating designer biological scaffolds into commercial products.

Fig. 1. Beta-sheet self-assembling peptide nanofiber scaffolds, hydrogel and cells embedded in the scaffold.

a Self-assembling peptide RADA16 molecular model. The calculated peptide dimensions are ~6 nm long depending on end capping, 1.3 nm wide and 0.8 nm thick. b Model of thousands of individual peptides as a single nanofiber. c Trilion of individual peptides self-assemble into nanofiber scaffold as revealed by the SEM. Scale bar = 0.5 µm. d RADA16-I peptide nanofibers scaffold hydrogel with extremely high-water content (99.5–99.0%, w/v water). An image of nanofiber scaffolds hydrogel of RADA16-I at 1% (10 mg/ml), 99% water (image courtesy of 3-D Matrix). e Murine neural stem cells are embedded in the nanofiber scaffold. The diameter of nanofiber is in the similar diameter as the cell produced extracellular matrix. f Red blood cells are embedded in the natural fibrin. g Dense RADA16 nanofiber scaffold. Billions of layers of interwoven nanofibers tightly keep blood cells in place thus preventing from bleeding.

Fig. 2. The assembly line of self-assembling peptides toward clinics.

a Molecular modeling for both all-atom and coarse-grained simulations of self-assembling peptides featuring different functionalizations are necessary to verify the self-assembling propensity and solubility of new sequences. b Nanofibers of self-assembling peptides scaffold hydrogels are subsequently tested with cells (either to be transplanted or from the target tissue) in vitro to verify cytotoxicity and biomimetic properties of the novel construct. c Synthetic self-assembling peptides are tailored into 3D constructs with densely seeded cells (image courtesy of Amanda Marchini), potentially leading to organoids in long-term cultures in serum-free conditions. d Selected self-assembling hydrogels (seeded with cells or loaded with drugs) are injected or positioned (after self-assembling) in in vivo animal models of the target pathology. All steps provide essential data for subsequent clinical approval.

Fig. 3. PuraStat^® made of self-assembling peptide nanofiber scaffolds and PuraStat^® accessories.

a 5 ml syringe with attached nozzle applicator, ready for use as a hemostatic agent during surgery after opening of the packaging and attachment of the nozzle applicator. b Endoscopic nozzle (160 mm) attached to a PuraStat^® syringe. c Laparoscopic nozzle.

Fig. 4. The chiral self-assembly D- and L-peptide system.

a Molecular models of d-EAK16 and l-EAK16. b CD spectra of d-EAK16 and l-EAK16 at 37 °C. c SEM photograph of l-EAK16 and d-EAK16. d The nanofiber scaffolds of the chiral self-assembling peptide (including Sciobio-II). e The nanofiber scaffolds used in 3D cell cultures. f The TEM images show the nanofiber scaffolds. g 3D cell culture as an ECM viewed by microscope. h SEM image of surface of cells covered by enclosed nanofibers. i Sciobio^® commercial products sold as prefilled, sterile chiral self-assembling peptides to hydrocolloid solution as Sciobio liquid wound dressing, used in cleaning, washing, and protecting superficial wounds, abrasions in the superficial dermis. It forms a protective layer and acts as 3D nanofiber scaffold with microenvironment to promote wound healing. j Other chiral self-assembling peptides (Sciobio^®, Saienbei, Nafumei, Nafujia, Nafubao, Nafubang) as cosmetics, facial mask, moisturizing lotion, eye cream, and tonic, or used in wound healing, tissue regeneration, and tissue cell and stem cell encapsulation. Updated information is available at www.sciobio.com (for images of i and j: reproduced by permission of Chengdu Sciobio Biotech, Co. Ltd, China, Copyright 2020). k The result to use Nafujia wound liquid dressing treat patients with chronic diabetic foot ulcer (I, before treatment, II, 47 days after, treated by Dr. Xia Yuping, international stoma therapist of vascular surgery, the First People’s Hospital, Yibin city, China); use Saienbei liquid dressing treat patients with deep second degree burn (III, before treatment, IV, 14 days after, treated by Dr. Zeng Shengqiang, TMC Hospital affiliated to Southwest Medical University); and use Nafujia and Saienbei liquid dressing treat patients with severe trauma (V before treatment, VI, 60 days after, treated by Dr. Wang Xiuying, Shexian Hospital, Hebei province).