Biodegradable scaffolds

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 ...

AI Technical Summary

Benefits of technology

[0173]The methods and compositions of the present invention provide numerous advantages. One of the advantages of the compositions of the present invention may lie in the compositions' mulitifunctionality, as the composition may have one or more of the following properties: optimal mechanical characteristic; injectability for irregular defects; and multiple (i.e. two or more) stages of bioactive release to enhance the bone healing process. The scaffold and compositions of the present invention may also be capable of providing one or more of the following advantages: i) cross-linking in situ, ii) conforming to a bone geometry, iii) providing immediate mechanical stability, iv) providing a continuous delivery of one or more active agents, which may be, for example, antibiotics and growth factors; v) promoting accelerated tissue regeneration and vi) degrading into benign by-products that may be resorbed and excreted by the body.

[0174]An additional advantage of the compositions of the present invention may be the ability to vary biodegradation and / or release rates of various components. For instance, the present compositions may allow for the biodegradation and / or release process to be adjusted to match the kinetics of the bone regeneration process and thus, progressively transfer the loads from the scaffold to the new tissue. The development of bone architecture may be naturally driven by the mechanical forces applied. As a result, osteoclasts may begin resorbing bone that is not subjected to the appropriate load and only remodel the newly formed bone in areas of high stress.

[0175]The tunability of both the release of active agents, such as therapeutic agents and / or imaging agents, and degradation rates of each individual component in the scaffold may also provide the ability to mimic and accelerate one or more natural regeneration processes. For instance, the scaffolds and compositions of the present invention may be designed to provide immediate stability to a minor or substantial bone defect. The present compositions and scaffolds of the present invention may also simultaneously initiate and / or accelerate the natural healing cascade.

[0176]Additional aspects of the present invention will now be described with reference to specific and non-limiting Examples.

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.

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