Three Dimensional Cell Protector/Pore Architecture Formation for Bone and Tissue Constructs

Abstract

Living cellular material is encapsulated or placed in a protective material (cell protector) which is biocompatible, biodegradable and has a three-dimensional form. The three dimensional form is incorporated into a matrix that maybe implanted in vivo, ultimately degrade and thereby by replaced by living cell generated material.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This is a divisional application of U.S. Ser. No. 11 / 132,028 filed May 18, 2005 entitled Three-Dimensional Cell Protector / Pore Architecture which is a non-provisional application of 60 / 644,421 filed Jan. 14, 2005 entitled Three Dimensional Cell Protector / Pore Architecture Formation for Bone and Tissue Constructs are incorporated herewith by reference and for which priority is claimed.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]The subject matter of this invention was supported, at least in part, by grants from the National Institutes of Health, NIDCR grant R01 DE 14190 thereby resulting in potential use and / or license rights in the U.S. government and / or other entities pursuant to grant terms.BACKGROUND OF THE INVENTION[0003]In a principal aspect, the present invention relates to a construct for protecting biologics (such as cellular materials, particularly living cellular materials) by use of three-dimensional pro...

AI Technical Summary

Benefits of technology

[0016]Thus this invention relates to methods and compositions of three-dimensional cell protectors inside a moldable and self-hardening implant thereby protecting living cells from any undesirable environment such as pH changes, ion activities and mechanical disruption during implant manipulation and placement. Disclosed cell protectors typically have unique structures including three-dimensional lattice-like structures with cells living inside them, zigzag or woven or curved structures, or three-dimensional web-like structures. After fulfilling their first function, these protectors dissolve away. Thus, they initially build or rest in highly-interconnected three-dimensional pore architectures, at a prescribed time (for example, after implant setting), to serve as cell activity passageways throughout the entire implant. The cell protectors / pore architecture builders possess designed sizes, diameters, interconnectivity, and controlled degradation rates matching their applications, so that the cells can be released at a predetermined time to migrate, interact, and secrete new bone and tissues inside and throughout the entire implant. Such protector degradation rates can be controlled from a few minutes to several weeks as needed. It further allows different cells [bone-growing cells (osteoblasts), blood vessel-growing cells (endothelial cells), cartilage growing cells (chondrocytes), implant-degrading and resorbing cells (osteoclasts), etc.] to be released at controlled times in tailored parts or layers of the implant.

[0017]One purpose of this invention is to develop improved tissue regenerating constructs useful for dental, periodontal, craniofacial, orthopedic and other tissue regeneration repairs. Thus living cells can be obtained from the same patient destined to receive an implant and can be greatly multiplied in vitro. Then when being placed into a surgical repair, the living cells are stored in engineered cell protectors embedded in a surgical self-hardening matrix material for a prescribed period of time so that the cells are not harmed by events such as matrix manipulation, the chemistry of the matrix environment or setting reactions. The protectors can be in the shapes of long tubes or rods or three-dimensional lattice-like structures. Once the surgical matrix material is manipulated into the surgical site and it is no longer harmful to the cells, the three-dimensional cell protectors dissolve, thereby freeing and releasing the cells inside and throughout the implant. Concomitantly, the dissolution of the protectors form three-dimensional rod-shaped pore architectures that are highly-interconnected throughout the interior of the implant. Therefore, the cells can migrate, interact and attach throughout the interior of the implant and form new bone or other tissues throughout the implant. Since the matrix is resorbable, new tissue can form and eventually there is no presence of a foreign implant or residual implant material remaining.

[0019]1. That is capable of containing and maintaining living cells prior to the implant formation and placement. This is advantageous because the cells are distributed throughout the entire self-hardening implant and are protected from mechanical and chemical damage during paste mixing, manipulation and setting of the implant matrix material, such as a moldable and self-hardening calcium phosphate bone cement. Other methods that seed cells only after the implant is formed or hardened only have cells on the surface or in a shallow surface layer. Methods that directly mix cells into the implant materials risk cell damage or death due to mechanical, thermal and chemical damages.

[0020]2. That has engineered three-dimensional lattice-like structures, zigzag or woven or curved structures, or three-dimensional web-like structures that can build three-dimensional pore architectures, thus allowing critically-important cell migration, interactions and nutrient access throughout the implant.

[0021]3. That has a controlled degradation rate for the cell protectors to match specific requirements, for example, to match the different setting times of various implant cements. Within or during a generally predetermined time period the cells are protected inside the protectors. After that, the protectors dissolve and the cells are promptly released and three-dimensional pore architectures simultaneously created in the implant. This also allows different cells, for example, bone-growing cells (osteoblasts), blood vessel-growing cells (endothelial cells), cartilage growing cells (chondrocytes), implant-degrading and resorbing cells (osteoclasts), to be released at different controlled times in tailored parts or layers of the implant. It also provides the versatility to be applied to a variety of implant materials with widely differing compositions, working and setting times.

[0025]2. Has controlled degradation rate for the cell protectors to match specific requirements, for example, to match the different setting times of various bone cements, within which the cells are protected and after which the cells are promptly released and pore architectures simultaneously created; and allows different cells (bone-growing cells, blood vessel-growing cells, or implant-degrading cells) to be released at controlled times in the tailored parts or layers of the in-situ hardening implant; and

Problems solved by technology

However, in these studies, no cells were mixed into the CPC paste.

Furthermore, there has been no mention in prior art of the design of cell protectors / pore architecture builders of three-dimensional lattice-like structures, zigzag or woven or curved structures, or three-dimensional web-like structures inside surgically placed implants.

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