Injectable cross-linked polymeric preparations and uses thereof

Abstract

A composition for promoting repair of damaged tissues, being a cross-linked alginate solution, which can be maintained in liquid form indefinitely (under constant conditions) and only gels in vivo. This cross-linked alginate solution is an ideal material to be used for tissue repair. Injection of said material into cardiac tissue post-myocardial infarct induced tissue regeneration. The invention provides such injectable solution, as well as compositions and method of preparation thereof. The invention also provides various methods and uses of the cross-linked alginate solution, for cardiac tissue regeneration, induction of neo-vascularization, enhancing SDF-1 expression and guiding stem cell chemotaxis, among others. A kit for tissue repair is also provided.

Description

FIELD OF THE INVENTION The present invention relates to injectable pharmaceutical preparations containing cross-linked polymer, particularly alginate, as an active ingredient, which polymer forms a hydrogel in vivo. The invention also relates to the various uses of the injectable cross-linked alginate preparations and to methods of treatment employing the same, particularly repair of cardiac tissue damage and ablation of cardiac arrhythmias. BACKGROUND OF THE INVENTION All publications mentioned throughout this application are fully incorporated herein by reference, including all references cited therein. Myocardial infarction (MI) results in acute loss of myocardium and in an abrupt increase in loading conditions that induces left ventricular (LV) remodeling [Sutton, M. G. and Sharpe, N. (2000) Circulation 101:2981-2988; Mann, D. L. (1999) Circulation 100:999-1008; Jugdutt, B. I. (2003) Circulation 108:1395-1403]. The early phase of LV remodeling involves expansion of the infarc...

AI Technical Summary

Benefits of technology

As described herein, the present inventors developed a cross-linked alginate biomaterial which flows as liquid but still maintains sufficient consistency until injection into the desired location in the body, where it forms a solid gel. Most surprisingly, injection of this cross-linked alginate biomaterial promotes regeneration of damaged myocardium and increase of its function, without the need of cell co-transplantation. Thus, the use of these injectable polymeric solutions to treat cardiac infarcts may be an efficient replacement for treatments based on embryonic cell transplantation, in the treatment of myocardial infarct (MI) and chronic heart failure (CHF).

Problems solved by technology

The early phase of LV remodeling involves expansion of the infarct zone, which may result in early ventricular rupture or aneurysm formation.

It results in progressive deterioration in contractile function, heart failure and death [Sutton, M. G. and Sharpe, N.

However, current clinical interventions to minimize the devastating effects of heart attack are frequently not sufficient to prevent irreversible damage, LV remodeling and subsequent development of heart failure and death [Khand, A. U. et al.

However, cell transplantation approaches may be of little clinical benefit when the local cardiac structure cannot support cell seeding because it is absent or seriously damaged.

This strategy, however, might be limited due to lack of appropriate cells, risk of surgical procedure, general anesthesia and restricted access to LV septum and inferior wall.

However, the behavior of the system was less than satisfactory.

However, the consistency of hydrogel-cell suspensions of the type described above is not totally satisfactory for the purpose of injection into patients in need.

In particular, the shortcoming of these injectable cell-alginate formulations which disallows its use in clinical trials is the inconsistent performance between lots, due to poor distribution of the components during formulation.

This may be a considerable disadvantage.

These are evident disadvantages in the rather long process of tissue regeneration.

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