Biodegradable polymers as biomaterials
Introduction
The last two decades of the twentieth century saw a paradigm shift from biostable biomaterials to biodegradable (hydrolytically and enzymatically degradable) biomaterials for medical and related applications [1], [2], [3]. The current trend predicts that in the next couple of years, many of the permanent prosthetic devices used for temporary therapeutic applications will be replaced by biodegradable devices that could help the body to repair and regenerate the damaged tissues. There are several reasons for the favorable consideration of biodegradable over biostable materials for biomedical applications. The major driving force being the long-term biocompatibility issues with many of the existing permanent implants and many levels of ethical and technical issues associated with revision surgeries.
Even though the biomedical applications of enzymatically degradable natural polymers such as collagen dates back thousands of years, the application of synthetic biodegradable polymers started only in the later half of 1960s [4]. However, the past two decades saw the development of a range of new generation synthetic biodegradable polymers and analogous natural polymers specifically developed for biomedical applications. The driving force is, in part, due to the emergence of novel biomedical technologies including: tissue engineering, regenerative medicine, gene therapy, controlled drug delivery and bionanotechnology, all of which require biodegradable platform materials to build on.
The slow evolution in the development of biodegradable biomaterials can be attributed to several unique challenges in developing resorbable clinical materials compared to developing commodity polymers. A biomaterial can be defined as a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body [5]. The essential prerequisite to qualify a material as a biomaterial is biocompatibility, which is the ability of a material to perform with an appropriate host response in a specific application. The tissue response to an implant depends on a myriad of factors ranging from the chemical, physical and biological properties of the materials to the shape and structure of the implant. In the case of biodegradable biomaterials, their active biocompatibility must be demonstrated over time. The chemical, physical, mechanical and biological properties of a biodegradable material will vary with time and degradation products can be produced that have different levels of tissue compatibility compared to the starting parent material.
Some of the important properties of a biodegradable biomaterial can be summarized as follows [6]:
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The material should not evoke a sustained inflammatory or toxic response upon implantation in the body.
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The material should have acceptable shelf life.
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The degradation time of the material should match the healing or regeneration process.
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The material should have appropriate mechanical properties for the indicated application and the variation in mechanical properties with degradation should be compatible with the healing or regeneration process.
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The degradation products should be non-toxic, and able to get metabolized and cleared from the body.
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The material should have appropriate permeability and processibility for the intended application.
Some of the inherent properties of polymeric biomaterials that can have an affect on their biocompatibility include: material chemistry, molecular weight, solubility, shape and structure of the implant, hydrophilicity/hydrophobicity, lubricity, surface energy, water absorption, degradation and erosion mechanism.
Given the complexity and the range of applications polymeric biomaterials are currently used, there is not just one polymeric system available that could be considered as an ideal biomaterial. This underlines the need for developing a wide range of biodegradable materials available for implant fabrication that can appropriately match the specific and unique requirements of each individual medical application.
Current efforts in biodegradable polymer synthesis have been focused on custom designing and synthesizing polymers with tailored properties for specific applications by: (1) developing novel synthetic polymers with unique chemistries to increase the diversity of polymer structure, (2) developing biosynthetic processes to form biomimetic polymer structures and (3) adopting combinatorial and computational approaches in biomaterial design to accelerate the discovery of novel resorbable polymers.
Biodegradable polymeric materials are being investigated in developing therapeutic devices such as temporary prostheses, three-dimensional porous structures as scaffolds for tissue engineering and for pharmacological applications, such as drug delivery (both localized and targeting systems). Some of the current biomedical applications of biodegradable polymeric materials include: (1) large implants, such as bone screws, bone plates and contraceptive reservoirs, (2) small implants, such as staples, sutures and nano- or micro-sized drug delivery vehicles, (3) plain membranes for guided tissue regeneration and (4) multifilament meshes or porous structures for tissue engineering [7]. A tissue engineering approach uses a biodegradable construct to assemble cells in three-dimensions to ultimately develop into functioning tissue. Polymeric materials with a wide range of mechanical and degradation properties are required to mimic the properties of various tissues. In controlled drug delivery, bioactive agents are entrapped within a biodegradable polymer matrix from which they are released in an erosion- or diffusion-controlled fashion or a combination of both. The release characteristics of the bioactive agents can be effectively modulated by suitably engineering the matrix parameters.
Due to the versatility of polymeric materials, they are rapidly replacing other material classes, such as metals, alloys and ceramics for use as biomaterials. In 2003, the sales of polymeric biomaterials exceeded $7 billion, accounting for almost 88% of the total biomaterial market for that year [8]. It is predicted that by 2008, the biocompatible materials market will reach $11.9 billion suggesting a huge market for polymeric biomaterials in the coming decades.
Section snippets
Biodegradable polymers
Both synthetic polymers and biologically derived (or natural) polymers have been extensively investigated as biodegradable polymeric biomaterials. Biodegradation of polymeric biomaterials involves cleavage of hydrolytically or enzymatically sensitive bonds in the polymer leading to polymer erosion [9]. Depending on the mode of degradation, polymeric biomaterials can be further classified into hydrolytically degradable polymers and enzymatically degradable polymers. Most of the naturally
Hydrolytically degradable polymers as biomaterials
Hydrolytically degradable polymers are polymers that have hydrolytically labile chemical bonds in their back bone. The functional groups susceptible to hydrolysis include esters, orthoesters, anhydrides, carbonates, amides, urethanes, ureas, etc. [10].
Two general routes are used to develop hydrolytically sensitive polymers for biomedical applications. They are step (condensation) polymerization and addition (chain) polymerization including ring-opening polymerization. Step process is used to
Proteins and Poly(amino acids)
Proteins, the major structural components of many tissues are essentially amino acid polymers arranged in a three-dimensional folded structure and are one of the most important class of biomolecules identified. Being a major component of the natural tissues, proteins and other amino acid-derived polymers have been a preferred biomaterial for sutures, haemostatic agents, scaffolds for tissue engineering and drug delivery vehicles. Furthermore, protein based biomaterials are known to under go
Conclusions
Most of the biodegradable materials currently on the market are based on natural polymers such as collagen and synthetic polymers such as poly(α-esters). Advances in synthetic organic chemistry and novel bioprocesses are enabling the development of a wide range of novel polymeric materials as candidates for developing transient implants and drug delivery vehicles. The success of biodegradable implants lies in our ability to custom design or modify existing biomaterials to achieve appropriate
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