Matrix composed of a naturally-occurring protein backbone cross linked by a synthetic polymer and methods of generating and using same
Inventors
Seliktar, Dror • Almany, Liora
Assignees
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Publication Number
US-9120872-B2
Publication Date
2015-09-01
Expiration Date
Abstract
A method of treating a disorder characterized by tissue damage is provided. The method comprising providing to a subject in need-thereof a composition which comprises a synthetic polymer attached to denatured fibrinogen or a therapeutic portion of the fibrinogen, the composition being formulated for releasing the therapeutic portion of the fibrinogen in a pharmacokinetically regulated manner, thereby treating the disorder characterized by tissue damage or malformation.
Core Innovation
The invention relates to a biosynthetic hybrid scaffold comprising a plurality of denatured fibrinogen molecules and a plurality of crosslinked synthetic polymers. Each denatured fibrinogen molecule is covalently attached to at least two crosslinked synthetic polymers, and the synthetic polymers are crosslinked between the polymers.
In the disclosed scaffold, the denatured fibrinogen can be provided as whole denatured fibrinogen or as fragmented denatured fibrinogen, including therapeutic portions. The hybrid scaffold is described as providing pharmacokinetically regulated release of fibrinogen therapeutic fragments, with release behavior linked to formulation parameters such as PEGylated denatured fibrinogen composition and scaffold formation as a 3D matrix or hydrogel.
The disclosure describes functionalized synthetic polymers, including PEG-Ac/PEG-DA and PEG-VS, and hydrogel crosslinking involving photoinitiated polymerization. Biological outcomes reported include enzymatic and controlled degradation of PEGylated denatured fibrinogen, chemotactic cell invasion in vitro, and osteogenesis and chondrogenesis in rat tibia and sheep osteochondral defect models.
Claims Coverage
The partial content identifies one independent claim (clm-00001). The core claim covers a hybrid scaffold structure with covalent tethering of denatured fibrinogen to multiple crosslinked synthetic polymers and crosslinking between the synthetic polymers, with further inventive refinements provided in dependent claims.
Hybrid scaffold of covalently attached denatured fibrinogen
A scaffold comprising a plurality of denatured fibrinogen molecules, where each denatured fibrinogen molecule is covalently attached to at least two crosslinked synthetic polymers.
Crosslinked synthetic polymers forming a scaffold
A scaffold comprising a plurality of crosslinked synthetic polymers, where the synthetic polymers are crosslinked between said polymers.
Overall, the claim coverage centers on a scaffold architecture where denatured fibrinogen is covalently linked to at least two different crosslinked synthetic polymers, and the synthetic polymers are crosslinked with each other.
Stated Advantages
Pharmacokinetically regulated release of fibrinogen therapeutic fragments.
Enzymatic and controlled degradation of PEGylated denatured fibrinogen.
Chemotactic cell invasion in vitro.
Osteogenesis and chondrogenesis in rat tibia and sheep osteochondral defect models.
Controlled neurite outgrowth from DRGs with growth factor delivery.
Documented Applications
Treatment of tissue damage or malformation via biosynthetic hybrid scaffolds that release fibrinogen therapeutic fragments.
Bone-related repair and osteogenesis in a rat tibia model using the disclosed hydrogel/scaffold compositions.
Cartilage-related repair and chondrogenesis in a sheep osteochondral defect model using the disclosed hydrogel/scaffold compositions.
Nerve-related regeneration support, including controlled neurite outgrowth from DRGs with growth factor delivery, with modulation by PEG-DA/fibrinogen composition.
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