Applications of Biodegradable Polymers in Medical

Biodegradable synthetic materials have been developed for various medical applications, including surgical implants in blood vessels, implantable matrices for controlled long-term drug release in orthopedic surgery, absorbable surgical sutures, and eye treatment. These materials are collectively known as biomaterials, which refer to non-living materials used in medical devices that interact with biological systems. The term biocompatibility has also been defined to describe how well a material can coexist with the body’s tissues without causing adverse reactions. Essentially, biocompatibility determines the ability of a material to interact with a specific host’s body without causing harm.

Surgical Sutures

When tissues are damaged, they can lose their structural integrity and may not be able to heal on their own. In such cases, the use of materials or instruments to hold the wound edges together can aid in the healing process. Sutures are a classic example of such materials, and synthetic, absorbable sutures have been widely used in surgeries since the 1960s due to their good tissue compatibility. Multifilament sutures made from PGA, PLA, and their copolymers are commonly used due to their good handling characteristics. However, monofilament sutures with smooth surfaces are more suitable for continuous sutures as PGA and PLA are too stiff and inflexible. Biodegradable polymers such as polydioxanones and polyglyconates, with their low bending moduli, are more flexible and can be used as sutures.

Dexon, made from poly(glycolic acid), was the first synthetic polymer developed for surgical thread production. It is a highly flexible thread with good knot security and undergoes hydrolytic decomposition in humans with minimal tissue reaction. Polygalactin 910 is another copolymer made from glycolide and lactide, which is commonly used as sutures. Its absorption period can be adjusted by using a smaller relative molecular mass. Monocryl is a copolymer of glycolide and ε-caprolactone that is nontoxic and causes a delicate reaction during absorption. Polydioxanone (PDS) is another polyester that offers essential mechanical resistance after implantation and can retain 70% of its initial resistance after 14 days. Nylon sutures are also biodegradable and cause moderate tissue reaction, but they undergo slow biodegradation and fragmentation after implantation.

Overall, biodegradable polymers offer several advantages over traditional metal implants and non-biodegradable materials. They can adapt to the dynamic processes of bone healing and degrade over time, eliminating the need for a second surgery for removal. In addition to sutures, they are also useful in other applications such as bone plugs and spacers.

Bone-Fixation Devices

While metal fixation is an effective approach for treating bones, metal and bone have distinct mechanical properties. The elasticity constant of bone is merely one-tenth of implanted steel, but its tensile strength is ten times lower. Hence, removing metal implants may lead to bone weakness and refractures. On the other hand, biodegradable implants can adapt to the dynamic processes of bone healing by decreasing the amount of weight-bearing material gradually. Over several months, the introduced material disintegrates, and there is no need to operate on the patient to remove it. PGA, PLA, PHD, and polydioxanone are potentially applicable in this field. Clinical studies have recommended using polydioxanones for protecting ligament augmentation, securing ligament sutures, and as a form of internal splinting suture to enable early motion after surgery. Biodegradable polymers are also useful in other areas. For instance, a marrow spacer can save autologous bone material. Plugs can be used to close bone marrow during endoprosthetic joint replacement. Polymer fibers can fill significant bone defects to avoid mechanical loads.

Vascular Grafts

Numerous studies have aimed to create satisfactory small-diameter vascular grafts. Nilu and colleagues developed vascular prostheses with matrices that could be absorbed by a developing anastomotic neointima. Their research demonstrated that a gelatin-heparin complex, when appropriately crosslinked, could serve as both a temporary antithrombogenic surface and an ideal substructure for the anastomotic neointima.

Adhesion Prevention

Preventing tissue adhesion after surgery is crucial to avoid potential complications. The ideal material for this purpose should be durable, yet flexible enough to cover the affected soft tissue tightly. Additionally, it should be biodegradable and absorbed into the body once the tissue has fully regenerated. Matsuda and colleagues developed photocurable mucopolysaccharides as materials for preventing tissue adhesion, which meet various requirements such as non-adherent surface characteristics, biocompatibility, biodegradability, and non-toxicity. These mucopolysaccharides were partially functionalized with photoreactive groups like cinnamate or thymine, and when exposed to UV irradiation, formed water-insoluble gels through intermolecular photodimerization of the photoreactive groups. The photocured films, which had lower degrees of substitution and high swellability and flexibility, were effective in preventing tissue adhesion and showed improved biodegradability. The researchers speculated that these newly developed gels may promote the healing of injured tissues in a bioactive way.

Artificial Skin

Biodegradable polymeric materials have been developed as artificial skin substitutes and wound dressings to treat burns. Commercially available artificial skins have mainly been composed of enzymatically degradable polymers like collagen and chitin. However, unfavorable qualities of native collagen have been reported, such as rod-like shapes and expression of collagenase genes to fibroblasts. To address these issues, new biomaterials have been developed.

Koide et al. [55] developed a sponge-like biomaterial that combines fibrillar collagen (F-collagen) with gelatin, physically and metabolically stabilized by introduction of crosslinks. Yasutomi et al. [56] developed a biosynthetic wound dressing with drug delivery capability, consisting of a spongy sheet based on a mixture of chitosan and derivatized collagen, laminated with a polyurethane membrane impregnated with antibiotics. This wound dressing is capable of suppressing bacterial growth and minimizing cellular damage.

Hybrid artificial skins are another important goal in biomedical engineering, where synthetic polymers and cell cultures are combined to form synthetic-biological composites. Biodegradable polymers can be useful as media for growing cells and tissue cultures in vitro.

Drug Delivery Systems

The use of biodegradable polymers has opened up a new avenue in drug delivery systems. Various degradable polymers, both natural and synthetic, have potential use in this area. The conventional methods of drug administration, such as injection or tablet, have limitations. The plasma levels of drugs tend to rise initially after administration but then fall drastically when the drug is metabolized, often leading to suboptimal drug plasma levels. Additionally, the drug may permeate throughout the body and not reach the specific site where it is required.

One solution to this problem is to use a controlled drug delivery system where the drug is released at a constant, predetermined rate, preferably at the specific location. One approach is to contain the drug in a polymer membrane or encapsulated in a polymer matrix, from which it gradually diffuses into the surrounding tissue. In some cases, the drug release is influenced by erosion or polymer dissolution. Biodegradable polymers like poly(lactic acid) or polyorthoesters are suitable for such drug delivery systems.

Some soluble polymers can be used as drug carriers. Researchers have developed polymers to which certain drugs are attached through lateral groups that can be released after cleavage of the bonds attaching them to the backbone. The targeting of drugs is achieved through the use of bonds that cleave only under certain conditions, allowing drug release at specific sites of action.

Efforts have been made to develop plastic biodegradable polymer materials. Researchers have mixed lactic acid oligomers with 1,2-propylene glycol or glycerol as plasticizers. Glycerol showed low compatibility, whereas propylene glycol showed high compatibility with the polymer at high concentrations. The mixtures exhibited a substantial decrease in processing temperatures and enhanced delivery of salicylic acid during the early stages of release. It is therefore feasible to obtain easy and safe drug delivery systems that can be injected into a body without requiring surgical retrieval after administration. The differential rates of drug release may also be advantageous when an increased drug dose is required at the beginning of therapy.

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