Written by Ashley Clarke (Chair) and Rosa Comas (Clerk)
Over time biomaterials have evolved from short-lived natural materials to long-lasting artificial materials, however current research has seen a shift back to materials which may be broken down by the body. During the industrial revolution and into the late 1800’s, although they deteriorated quickly, wood and bone were widely used as biomaterials to replace teeth and limbs. Around the end of the first World War, biologically inert pure metals became popular for both surgical instruments and implanted biomaterials. Later, in the mid 20th century, ceramics were investigated due to their ability to bond with living tissues, and the possibility for customization of mechanical and physical properties were realized with synthetic polymers. Today, biomaterials in development are no longer inert but are capable of positively interacting with surrounding tissues to improve wound healing and/or biomaterial performance – and some have potential to disappear after healing is complete.
In our first meeting of the series, Science Club discussed the major characteristics of biomaterials and biocompatibility including the use of metals, ceramics, and polymers in biomedical devices. This week we focused on biodegradable polymers and metals and their advantages/disadvantages compared to traditional polymeric and metal biomaterials.
Biodegradable materials cannot fully replace the library of biomaterials available today but may demonstrate additional characteristics well-suited for some permanent implants and drug delivery devices. There are many issues with using permanent materials for implants, including physical irritation, stress shielding, accumulation of metal in tissues, and chronic local inflammation. Cardiovascular devices also have potential for thrombogenesis and extended endothelial dysfunction, and implants in children cannot adapt as they grow. In some cases, repeat surgery is required to remove implanted materials after healing – whereas a biodegradable biomaterial used for the same purpose would allow for increased physiological repair and possibility of tissue regrowth in place of the degraded implant. Other characteristics of a functional biodegradable biomaterial may include:
- sufficient strength until surrounding tissue has healed
- does not cause an irregular or long-term inflammatory response
- is not carcinogenic, teratogenic, mutagenic, or toxic at any stage in degradation
- can be metabolized by body after fulfilling its purpose
- is easily processable
- has an acceptable shelf life
- can be sterilized
There are many possible mechanisms of degradation for materials in vivo, including stress cracking, fatigue cracking, hydrolysis, oxidation, and degradation by enzymes. It is typically a combination of these factors which ultimately leads to the breakdown of a material, however some will occur more naturally than others. Many synthetic polymers are prone to hydrolyzation due to their chemical makeup, including esters, anhydrides, amides, orthoesters, acetals, urethanes, and ureas – however the rate of degradation is affected by a combination of many other factors – bond stability, hydrophobicity, initial molecular weight, crystallinity, and glass transition temperature, to name a few. An advantage of using synthetic polymers as biodegradable materials is the ability to adjust each of these factors to help control the material’s properties and degradation rate. For example, polycaprolactone (PCL) undergoes slow degradation due to hydrolysis of its ester linkages and has been used in FDA-approved drug delivery devices and sutures. Another synthetic polymer, poly(lactide-co-glycolide) (PLGA) degrades much faster although through a similar mechanism, but by adjusting the ratio of the monomers the crystallinity and rate of degradation can be manipulated. Polymers may also encapsulate living cells or biomolecules which aid in the healing process, however most degraded synthetic polymer by-products cannot be fully resorbed and are instead excreted by the body.
Figure 1: Methods of drug encapsulation in polymers. Source: Maarten Janssen et al. Polymers, 6(3), pp. 799-819, 2014.
In comparison, natural polymers are collected from natural materials and adapted for use in degradable biomaterials. Natural polymers such as collagen, cellulose, chitosan, and alginate are commonly used in skin grafts and as cell scaffolds in tissue engineering and have potential for use as drug delivery devices. One benefit of using natural polymers is that they typically do not elicit as large of an immune response upon implantation and once broken down their components may be reused within the body, although their mechanical and physical properties may not be as manipulative as with synthetic polymers. Some natural polymers may also exhibit antibacterial properties which help protect wounds from infection during the healing process.
Metallic alloys have also been investigated as potential degradable biomaterials for applications requiring materials stronger than polymers. Alloys of metals such as magnesium, iron, lithium, and calcium are of particular interest since these elements are present in the body and have potential to be resorbed as the biomaterial degrades. Although some of these metals are essential building blocks for biological materials, in large concentrations they are toxic to tissues. One of the major roadblocks in degradable metals development is fast oxidation resulting in early deterioration of mechanical properties and large ion concentrations in tissues. However, with the right degradation speed, these materials have potential to be fully resorbed by the body and beneficially used to build new muscle and bone tissues.
Near the end of our session, the Science Club divided into two groups to discuss the advantages and disadvantages of choosing a polymer, biodegradable polymer, metal, or biodegradable metal for use in an implanted medical device. Group 1 discussed orthopedic applications while Group 2 discussed vascular applications.
Figure 2: Magnesium-calcium alloy screws (left) and titanium stent with a carbon-based coating (right). Sources: https://www.hzg.de/public_relations_media/news/045928/index.php.en (left), http://www.ionbond.com/en/coating-services/medical/cardiovascular/ (right).
Group 1 suggested the use of a magnesium alloy for an orthopedic screw. The metal would provide sufficient strength to support the bone while healing in addition to providing metals used in bone healing during the degradation process. Although there are many difficulties predicting the degradation and change in properties of the magnesium implant as it degrades, in load-bearing applications a polymeric screw may not provide sufficient support. Another suggestion was to create a screw out of poly(lactide) (PLA) and hydroxyapatite particles. PLA is degradable and bioresorbable, while hydroxyapatite would provide additional strength and encourage bone regeneration. Hydroxyapatite is the main component of bone, and so is bioresorbable as well. For bone defects, a hydrogel or 3D printed implant could be used to fill the space. Group 2 suggested a multi-layered material for a cardiovascular stent, with metal mesh at its core and an exterior polymeric coating to both protect the metal from oxidation and to encapsulate a drug beneficial to the healing process. It’s important the stent is both flexible and strong to be able to move with the blood vessel walls while preventing obstructions such as plaque from blocking blood flow through the vessel. It was suggested that heparin be added for its non-thrombogenic properties. Drug could be added either by dipping the metal stent into a solution of the polymer containing the drug, or by binding the drug onto the surface of the metal or polymer.
Collectively the following summary of properties for biodegradable materials was created:
|Advantages||– Good biocompatibility
– Customization of properties, both bulk and surface
– Ability to immobilize substances within to aid with healing (eg. cells, drugs)
|– High initial biocompatibility
– Alloy’s elements will be resorbed by the body
– Magnesium alloys provide strength but are also compatible with CT and MRI scans
|Disadvantages||– Poor mechanical properties
– Difficult to predict mechanism of degradation
– Potential presence of toxic substances when broken down such as monomers or additives (for synthetic polymers)
|– Biocompatibility is reduced if metal ions accumulate in tissue
– Corrosion rate is too fast, so degradation occurs before the healing process is complete
– Drastic change in mechanical properties during degradation
Thanks to everyone who came to this week’s session, and if you were interested in learning about the relationship between materials and tissues, make sure you don’t miss this week’s session focusing on responsive and ‘smart’ biomaterials!