Composite scaffolds and methods using same for generating complex tissue grafts

Abstract

A composite scaffold for engineering a heterogeneous tissue is provided. The composite scaffold includes: (a) a first scaffold being capable of supporting, formation of a first tissue type thereupon; and (b) a second scaffold being capable of supporting formation of a second tissue type thereupon; wherein the first scaffold and the second scaffold are arranged with respect to each other such that when the first scaffold supports the first tissue type and the second scaffold supports the second tissue type, a distance between any cell of the second tissue type and the first tissue type does not exceed 200 $G(m)m.

Description

FIELD AND BACKGROUND OF THE INVENTION[0001] The present invention relates to composite scaffolds capable of supporting growth of complex tissue and to methods of manufacturing and using same.[0002] Traditional medical treatments for functional deficiencies in organs have focused on using pharmaceutical compositions for replacing such functional deficiencies. However, in some cases, pharmaceutical replacement therapy cannot be instated since organ function is oftentimes complex and / or not completely understood.[0003] In such cases, the only viable alternative is surgical replacement of the non-functional organ, however, in most cases, organ transplantation requires continuous use of immunosuppressive agents to prevent immunological rejection of the organ, depriving the patient of the full protective function of the immune system.[0004] Moreover, the need for donor organs far exceeds the supply. Organ shortage has resulted in new surgical techniques, such as splitting adult organs for...

AI Technical Summary

Problems solved by technology

However, in some cases, pharmaceutical replacement therapy cannot be instated since organ function is oftentimes complex and / or not completely understood.

In such cases, the only viable alternative is surgical replacement of the non-functional organ, however, in most cases, organ transplantation requires continuous use of immunosuppressive agents to prevent immunological rejection of the organ, depriving the patient of the full protective function of the immune system.

Moreover, the need for donor organs far exceeds the supply.

Organ shortage has resulted in new surgical techniques, such as splitting adult organs for transplant.

Despite fairly good results, such techniques still suffer from a lack of donor tissue.

The lack of viable donor tissue has led to the emergence of methods directed at generating engineered tissue for use in replacement procedures.

The resultant bonded fiber structure of Polymer A has substantial rigidity, but the number of pores and their distribution is limited by that of the fiber mesh used in the fabrication.

However, the maximum level of porosity in this process is limited due to the difficulty of suspending salt particulates in the polymer solution.

Furthermore, the crystalline structure of the sodium chloride salts gives rise to sharp edges which line the pores of the resulting foam, substantially reducing cell growth within the pores.

Nevertheless, complex shaped implants cannot be easily compacted and the process is rather time-consuming.

Many of the above-described scaffold fabrication techniques generate scaffolds with inherent limitations.

Since such techniques require the use of severe heat or chemical treatment steps, cell seeding cannot be initiated during scaffold fabrication.

In addition, chemical treated scaffolds can often invoke an inflammatory response following implantation.

Although numerous scaffold designs suitable for generating engineered tissues are known in the art, tissues engineered using such scaffolds typically lack the full functional capabilities of natural tissues.

This is due to the fact that such scaffolds are either incapable of generating complex tissues having a fully functional architecture (e.g., vascularized), or are incapable of supporting growth of complex tissues altogether.

However, presently fabricated bioartificial implants, has proven to be unsatisfactory for a variety of reasons, including, poor biocompatibility, engraftment failure or tissue dysfunction.

One of the major problems of bioartificial implants is the need for a well branched vascular network, which can providing the engineered tissue with continuous supply of oxygen and nutrients at the transplantation site.

To date all attempts to address this issue have resulted in poor vascularization of engrafied tissues.

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