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Amphiphilic, Anionic Peptide Hydrogels

Peptides can be designed de novo to mimic native proteins with unique chemical and physical properties that are a direct result of their amino acid composition. Peptide synthesis technology enables the production of any desired sequence with high purity level that is further enhanced by standard chromatographic procedures.

Amphiphilic beta-sheet biomaterials that are created by peptides with alternating hydrophobic and hydrophilic amino acids, form hydrogels composed of fibrils. These structures are stabilized in molecular bilayers with hydrophilic groups pointing to the aqueous phase, and hydrophobic ones zipping the interior of the fibrils off the solution.


Bone Sci. develops amphiphilic and anionic beta-sheet peptides, for example PFD5, that form anionic hydrogels for applications in bone and cartilage tissue healing and regeneration.

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A) PFD5 molecules in bilayer motif composing hydrogel fibrils. B) A fibril of PFD5 anionic amphiphilic hydrogel matrix [1]

Bone Biomineralization

Bone is a unique rigid tissue reinforced by ~ 70 % of the mineral hydroxyapatite. Bone biomneralization is orchestrated by a group of extracellular anionic rich proteins as osteopontin, bone sialoprotein, dentin matrix protein-1, ameloblastin and amelogenin. PFD5 forms hydrogels that mimic the extracellular matrix, created by these proteins.

Bone Sci. PFD5 hydrogels, when loaded with calcium phosphate mineral, induce biomineralization and bone tissue formation via a novel mechanism that emphasizes the importance of calcium ion availability to bone remodeling. Mineral-loaded PFD5 hydrogels were found to significantly improve bone regeneration in rat femora and in sheep epiphysis models with different types of Ca/P particles, promoting their turnover through cellular processes into bone tissue.


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TEM images of amphiphilic anionic hydrogels. A) Fibrils constructing the matrix. Scale bar 200 nm B) Fibrils of PFD5 nucleating calcium phosphate in simulated body fluid. Scale bar 500 nm [2,3]


Histological sections of rats femora 6 weeks post-surgery stained by Masson’s trichrome. Sagittal views of (A) b-TCP treated femur and of (B) b-TCP loaded PFD5 hydrogel treated femur. Black arrows show the borderline between newly formed bone tissue and existing bone tissue. (C) Section marked by a frame in (B), magnified (x10). Black arrows indicate the front line of tissue regeneration. Black triangles indicate bone regeneration process also in cortical bone. [4]

Sustained Drug Release

PFD5 peptide forms an amphiphilic hydrogel matrix ideal for local delivery of certain drugs to vicinity of injected site bone or cartilage. Our lead product BS-101 (PeptOss) releases the antibiotic drug Minocycline HCL over a few weeks. 


1. The effect of pH and calcium ions on the stability of amphiphilic and anionic β‐sheet peptide hydrogels. S Zarzhitsky, H Edri, Z Azoulay, I Cohen, Y Ventura, A Gitelman, H Rapaport. Peptide Science 100, 760-772, 2013.


2. Hydrogel scaffolds of amphiphilic and acidic β‐sheet peptides. H Rapaport, H Grisaru, T Silberstein. Advanced functional materials 18, 2889-2896, 2008.


3. Matrices of acidic β‐Sheet peptides as templates for calcium phosphate mineralization. S Segman‐Magidovich, H Grisaru, T Gitli, Y Levi‐Kalisman, H Rapaport. Advanced Materials 20, 2156-2161, 2008.


4.  Acidic peptide hydrogel scaffolds enhance calcium phosphate mineral turnover into bone tissue. N Amosi, S Zarzhitsky, E Gilsohn, O Salnikov, E Monsonego-Ornan, R Shahar, H Rapaport. Acta biomaterialia 8, 2466-2475, 2012.