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Biodegradable scaffolds

a biodegradable and scaffold technology, applied in the field of biodegradable scaffolds, can solve the problems of decelerating the release of integrated antibiotics, serious and life-threatening, bacteria infection is one of the most common problems, etc., and achieves the effects of enhancing bone healing process, ensuring mechanical stability, and optimal mechanical characteristics

Inactive Publication Date: 2013-07-18
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a new composition that can be used as a scaffold for treating bone defects. It comprises a biodegradable polymer matrix and biodegradable reinforcing particles dispersed in the matrix. The composition can also contain a porogen particle that helps to induce bone growth. Additionally, the composition can be associated with various active agents such as therapeutics, antiobiotics, proteins, and cells. The methods and compositions of the invention have various applications including bone healing, tissue engineering, and prevention or treatment of microbial infections.

Problems solved by technology

Bacterial infection is one of the most common problems after orthopedic implant surgery.
If not prevented, bacterial infection may result in serious and life threatening conditions, such as osteomyelitis, which has shown a great necessitate for local antibiotic delivery systems in the treatment of infections.
It has shown that surface modification of MPS leads to decelerating the release of the integrated antibiotics.
Despite particular treatment, open fractures (broken bones in communication with the environment) present high rates of complications because of the risk of bacterial infections and chronic osteomyelitis that can threaten the viability of the limb and even the life of the patient.
Standard care for open fractures requires irrigation, debridement, stabilization, and antibiotic therapy and often results in multiple procedures according to the severity of the wound and the onset of infections.
The lack of proper control over a drug release rate and target delivery area is a huge disadvantage for conventional drug tablets.
Tablets tend to provide rapid and immediate release of therapeutic agents and require more frequent and repeated dosages for maintaining therapeutic levels, causing unwanted fluctuations in drug amounts delivered to the blood and tissue.
Localization, controlled release, and sustainability of drugs over long periods of time within the body may be some of the challenges in the design of effective drug therapies.

Method used

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  • Biodegradable scaffolds
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Examples

Experimental program
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Effect test

example 1

Scaffold Components

[0177]FIG. 1 shows alginate hydrogel microspheres encapsulating cells and bioactive molecules. Inside of the above porogen (˜200-500 microns) is PRP as well as mesenchymal stem cells (top left and center optical image, right confocal image green-cells, bottom SEM image). Also within the porogen may be microparticles or nanoparticles, which may be coated with a polymer, such as agarose or PLGA, that may also contain one or more active agents loaded within the nanopores (FIG. 2).

[0178]The porogen may be dispersed within a viscous polymer matrix, such as a PPF matrix, that may contain silica nanorods as mechanical reinforcement (FIG. 3). In some embodiments, the composition with some or all mentioned components may be loaded into a syringe and injected into the bone defect where it may crosslink in the shape of the bone defect geometry (FIG. 4). Yet, in some embodiments, the composition may be used for forming a scaffold ex situ. After cross-linking, the scaffold com...

example 2

Release of Active Agents from Scaffolds for Treatment

[0179]The multifaceted nature of the injectable matrix may provide ideal means of staggering the delivery of the above-mentioned active agents that may enhance stem cell activity at rates contingent upon the corresponding stage of fracture healing. For example, PRP may provide a cocktail of all necessary growth factors with the additional advantage of presenting them in optimal ratios for cell growth. PRP may therefore be a supplier of bioactive molecules throughout the entire scaffold and may be contained in one or more components of the composition and a scaffold formed therefrom, such as the porogen particles, the reinforcing microparticles or nanoparticles, the microparticles or nanoparticles with the porogen particles and the polymer matrix. In some embodiments, PRP may be contained in more than one of the above mentioned components of the composition or the scaffold. In some embodiments, PRP may be contained in each of the a...

example 3

Synthesis, Characterization and Use of Alginate Porogens

[0186]The following example provides steps for incorporation of cells and platelet-rich plasma (PRP) and bioactive molecules into an alginate microsphere matrix during a fabrication process.

[0187]Protocol for Synthesis of Alginate Porogen Microparticles with the Incorporation of Cells and Platelet-Rich Plasma

[0188]As depicted in FIG. 7C, Calcium alginate beads were synthesized by emulsion in mineral oil with low surfactant conditions and acetic acid as a catalyst. In order to optimize the process and accomplish beads with sizes ranging from 300-500 μm, the concentration ratio of sodium alginate and platelet-rich plasma, the amount and type of surfactant, the stir rate and size of beaker and stir bar used for creating an optimal volume were all varied within the same protocol. Select runs of this process are provided in Table 1 below.

TABLE 1Runs 1-6: Variables manipulated, values employed, bead size range obtained.PercentSurfact...

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Abstract

In some embodiments, the present invention provides compositions that comprise: (1) a biodegradable polymer matrix; and (2) at least one biodegradable reinforcing particle that is dispersed in the matrix. In some embodiments, the biodegradable reinforcing particle is selected from the group consisting of porous oxide particles and porous semiconductor particles. In additional embodiments, the compositions of the present invention further comprise a (3) porogen particle that is also dispersed in the matrix. In further embodiments, the compositions of the present invention are also associated with one or more active agents. In various embodiments, the active agents are associated with the biodegradable polymer matrix, the biodegradable reinforcing particle, and / or the porogen particle. In various embodiments, the compositions of the present invention may be utilized as scaffolds, such as scaffolds for treating bone defects. Further embodiments of the present invention pertain to methods of making the compositions of the present invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Patent Application No. 61 / 363,835, filed on Jul. 13, 2010 and U.S. Provisional Patent Application No. 61 / 363,126, filed on Jul. 9, 2010. The entirety of each of the above-identified applications are incorporated herein by reference.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with government support under DARPA Grant No. W911NF-09-1-0044, awarded by the U.S. Department of Defense. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Current compositions and methods for tissue engineering or wound healing through the use of scaffolds suffer from various limitations. Such limitations may include insufficient biocompatibility, insufficient biodegradability, lack of mechanical stability, and insufficient porosity for the delivery of active agents. Therefore, there is currently a need to develop new methods and compositions for ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61L27/56
CPCA61L27/446A61L27/54A61L27/56A61L27/58A61L2430/02A61L2300/406A61L2300/41A61L2300/44A61L2300/64A61L2300/252A61L27/16A61L27/18A61L27/20A61L27/3834A61L27/3847
Inventor FERRARI, MAUROBUCHANAN, RACHELSMID, CHRISTINETASCIOTTI, ENNIO
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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