Washington University

Unversität Zürich

Eidgenossische Technische Hochschule Zurich

Other

Shelly E Sakiyama-Elbert

Jeffrey Alan Hubbell

Younan Xia

Jingwei Xie

Jason Schense

Stavros Thomopoulos

Matthew Silva

Richard Gelberman

Andrea Schwartz

A growth factor delivery scaffold combines a heparin/fibrin-based delivery system (HBDS) with a backbone based on polymer nanofibers for tissue (e.g., tendon and ligament) repair. The scaffold has improved surgical handling properties compared to the gelatinous consistency of the prior art HBDS system and retains the capability for delivering mesenchymal cells and controlling the release of growth factors. One application for the scaffold is mesenchymal stem cell (MSC) therapy for flexor tendon repair. The scaffold can deliver growth factors in a sustained manner, can be implanted for flexor tendon repair, is biocompatible, and is not cytotoxic. The growth factor delivery scaffold may also be used in the surgical repair of an injury to bone, muscle, cartilage, or other tissues.

Polymer nanofiber scaffold for a heparin/fibrin based growth factor delivery system

Polymer nanofiber scaffold for a heparin / fibrin based growth factor delivery system

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

Growth factor modified protein matrices for tissue engineering

Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling, and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, enzymatic action, and/or diffusion. In one embodiment, a fusion protein, which contains a crosslinking region, such as a factor XIIIa substrate, and a native protein sequence, such as a bioactive factor, is constructed. Degradable linkages may be included between the crosslinking region and the bioactive factor.

Matrices that support cell adhesion and growth are disclosed that deliver low heparin-binding affinity growth factor protein peptides in a controlled manner. These matrices comprise covalently or non-covalently bound heparin or heparin-like polymers, which serve to sequester the low heparin-binding affinity growth factor protein peptides within the matrix. The controlled release of some low heparin-binding affinity growth factor or peptides thereof occurs by degradation of some matrix component or dissociation of the low heparin-binding affinity growth factor protein peptides from the bound heparin. This differs from many controlled delivery devices in that release is not controlled solely by diffusion, and the rate of release may therefore be regulated by altering the rate of degradation of the matrix component or the amount of heparin bound within the matrix. The controlled release of such low heparin-binding affinity growth factor proteins such as NGF-&bgr;, NT-3 and BDNF, is demonstrated. The invention also identifies basic domains that can be utilized to identify other low heparin-binding affinity growth factor protein peptides useful in delivery as part of the matrices described herein.

Controlled release of non heparin-binding growth factors from heparin-containing matrices

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St. Louis, MO, United States of America

Shelly E Sakiyama-Elbert