Tissue Implants - Biological & Synthetic Materials PDF

Tissue Implants – Biological Materials and Synthetic Materials Lectures 9 & 10 Learning Points 1. Tissue Implants - Background 2. Biological Implants ◦ Autografts ◦ Homografts 3. Synthetic Implants – injectables, solids, meshes 4. Case Study – Tissue/Vessel Mimicking Materials  Tis...

Tissue Implants – Biological Materials and Synthetic Materials Lectures 9 & 10 Learning Points 1. Tissue Implants - Background 2. Biological Implants ◦ Autografts ◦ Homografts 3. Synthetic Implants – injectables, solids, meshes 4. Case Study – Tissue/Vessel Mimicking Materials  Tissue Implants - Background The development of tissue implant materials, both biological and synthetic, has occurred via two almost independent pathways: 1. Surgeons have pioneered the development of biological graft materials 2. Scientists and engineers have largely been responsible for introduction of synthetic polymers in a variety of medical applications. “Iron” Polymer: Ultra-High- Molecular-Weight Polyethylene Implant Has Successfully Replaced Bone Tissue – Science, March 2017  Facial Implants Increased sophistication of facial plastic surgery has led to increased numbers of procedures to correct genetic, traumatic, and cosmetic deformities as well as an increased expectation for positive results by the patient. As our population ages so do the demand for procedures that minimise cosmetic changes associated with ageing. The growing awareness of cosmetic procedures as well as the patient’s expectations for ideal results has led Facial Implant Market Size & Share, Industry to a need for improved techniques and implants for each procedure. Report, 978-1-68038-500-7 Grand View Research 2016  Anatomy and physiology of facial structure Facial implants are used in many areas of the face, chin, nose, forehead to name just a few. Facial structures that are replaced or that interface with implants include skin, cartilage and bone. The physical properties of skin, cartilage and bone are important considerations in the design of biomaterials.  Skin: highly extendable and can absorb impact loads without permanent deformation.  Cartilage: highly hydrated, behaves similar to skin in terms of its stress-strain behaviour. Both tissues can undergo almost 100% tensile deformation prior to failing.  Initial loads applied to cartilage are dissipated by rapid elastic deformation; however, with increasing time the load is dissipated (stress relaxation) by displacement of water molecules from the spaces between the collagen fibres. Cartilage shows increased modulus as the strain is increased (non-linear stress-strain behaviour).  Anatomy and physiology of facial structure Bone: initially exhibits an almost linear stress-strain curve which plateaus at strains of about 1% depending on the strain rate. Typical stress strain curves for different tissues: https://www.slideshare.net/coachademia/tendon-mechanics-lecture  Facial Implants: Biological vs Synthetic A considerable number of procedures in facial plastic surgery involve the use of either biological or synthetic materials. The ideal implant in the face must be permanent and must not stimulate a chronic inflammatory response, since any change in implant position or size will negatively affect the long-term outcome of a procedure. Both biological and synthetic implants have significant merits in a variety of applications.  Biological Implants - Types Autografts: A tissue or organ grafted into a new position in or on the body of the same individual. Cartilage autografts are perhaps the most widely used implants in the face: continue to grow when implanted into young hosts do not appear to resorb over periods of time as long as 12 years remain visible after transplantation Factors important in graft survival: the absence of dead space or blood in the surgical field graft smoothness curvature of the implant Contact with adjacent cartilage and adequate coverage with soft tissue are required for long-term survival  Biological Implants - Types Factors important in survival of cartilage grafts: Factor Outcome Blood Graft resorption (the graft breaks down and disappears) Dead Space Infection Rough Surface Graft resorption Curved Implant Warping or shape change No Cartilage interface Graft resorption Thin skin covering skin breakdown -> Extrusion of implant  Biological Implants - Types Homografts: A graft of tissue obtained from a donor of the same species as the recipient, i.e. tissue transplant between two humans. Fresh cartilage autografts are the material of choice for facial reconstruction in the area of the nose; however, this material is not always available in large amounts or a second surgical procedure is not warranted. An alternative is to use preserved cartilage as a homograft material. The down side of this approach is that the preservation technique must be shown to kill all viruses and infectious agents that may be transmitted via transplantation. In order for a cartilage homograft to be useful, it must be preserved between the time it is harvested and the time it is ready to be used. Preservation is accomplished by: Cold storage in saline, antiseptic or antibiotic solution Freeze drying Irradiation Exposure to these treatments is designed to maintain sterility of the graft, destroy any viral contaminants and reduce absorption. Homografts are not matched for histocompatibility antigens since graft rejection is not observed. The lack of a rejection reaction is possibly due to the avascularity of cartilage.  Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial – Imperial College London, 2010 study https://www.thelancet.com/action/showPdf?pii=S0140-6736%2810%2960828-8  Grafts not always from humans: Small-intestine submucosa (SIS) ”A material derived from the small intestine of a pig – is revolutionizing many medical procedures. Once applied to skin wounds or sutured internally, the material prompts the body to build new tissue, replacing the intestine- derived material with new human or animal tissue. Moreover, the replacement tissue matches the tissue that existed originally in that part of the body. Once SIS is placed within a body, it aids in the proliferation of new blood vessels, which is important for the wound-healing process. The https://www.cookbiotech.com/technology/ blood vessels nourish the graft and supply vital molecules that the body needs to rebuild the https://www.purdue.edu/uns/html4ever/0002 damaged tissue. The material also strengthens.Badylak.SIS.html in response to stress, much like natural tissue.”  Bone Grafts Bone grafts: can be either free or in combination with their vascular supply. Free grafts are used to repair facial defects, and bone grafts (including their blood supply) are used in facial plastic surgery. Grafts including arterial and venous vascular tissue are harvested and then connected to vascular tissue at donor sites. E.g. Iliac crest is used in the head and neck to fill in mandibular (jaw bone) defects greater than 1 mm in size. E.g. Split ribs are taken from the fourth, fifth or sixth rib. They can be used to reconstruct mid-facial deformities, mandible, and alveolar ridge.  All free bone grafts resorb which is a disadvantage of their use. The rate of resorption depends on the mobility of the graft, the degree of vascularisation and the site of implantation.  Synthetic Implant Materials Synthetic implants: offer a number of advantages over tissue grafts. Eliminates the time required to secure the graft Eliminates the pain and risk of infection or sickness associated with a second surgical site. Implants for standard procedures such as chin and cheek augmentation come in a variety of sizes and shapes. Some materials like silicone rubber and Teflon can be easily carved by the surgeon to modify an existing implant shape or size. A number of materials are used in facial applications including: Collagen Polydimethyl siloxane / Silicone Polyterafluroroethyolene / Teflon Polyethylene Polyethylene terephthalate / Dacron Polyglycolic acid Synthetic Implant Materials Outline of ideal augmentation material 1. Mechanical properties similar to host tissue 2. Persistent over long periods of time (does not degenerate) 3. Long shelf-life at room temperature 4. Ease of implantation 5. Chemically inert (does not cause inflammation) 6. Non-toxic, non-carcinogenic, non-allergic 7. Availability at a low cost 8. Capable of repeated sterilisation to avoid wastage 9. Corrects defects in one session  Synthetic Implant Materials Implants in the face can be arbitrarily classified by their physical form: liquids (injectables), solids and meshes. The host reaction to synthetic implants varies widely depending on the degradation rate and porosity of the materials.  Porous mesh implants allow extensive ingrowth and are effectively fixed to the tissue by fibrous tissue.  Solid implants have minimal porosity and therefore are held in place by fibrous tissue that forms a capsule surrounding the implant.  Polyglycolic acid and collagen are rapidly replaced by fibrous tissue; even by overcorrection using a large implant, the defect may not be permanently removed. Systemic antibiotics are recommended to be used before and after the procedures performed using the implants. Many implants are soaked in antibiotic solutions or antibiotic solution is forced into the pores within an implant by freeze-drying or exposing the implant to an antibiotic solution under vacuum. Synthetic Implant Materials Injectables: A number of injectable polymers are used to augment tissues of the face. They include polydimethylsiloxane, also known as silicone, and collagen. Silicone is used to remove depressions or wrinkles. (Silicone: used to refer to polymers that contain the element Silicon) Collagen is used in an injectable form to remove depressions and wrinkles and mask acne scars. Injectable Collagen: Correction with this material requires continuous maintenance due to the limited persistence of the implant (6 to 9 months). Patients must be carefully selected and a skin test conducted prior to injection in the face to minimise the possibility of adverse reactions. The amount of collagen to be injected into sites chosen for tissue augmentation is judged based on the degree of resorption at the test site.  Synthetic Implant Materials - Facial Solid Facial Implants: Four polymers are used in facial implants: polydimethylsiloxane (PDMS), polyterafluroroethyolene (PTFE), polyethylene and polyacrylate. The first two polymers PDMS and PTFE are the most widely used. Polydimethylsiloxane (PDMS) Solid Implant widely used in areas of the face including the chin and cheek available as a gel-filled implant for augmentation of soft areas and in rubber form for areas of the face that are stiffer Implants inserted after soaking in an antibiotic solution; patients are given antibiotics before and after surgery Infrequent Complications PDMS – “silly putty”  Bone erosion  Bleeding  Implant Extrusion  Improper Positioning  Infection (dead space) Other use of solid implants: https://www.jove.com/video/58590/synthesis-soft-polysiloxane-urea- elastomers-for-intraocular-lens  Synthetic Implant Materials Polyterafluroroethyolene (PTFE) - Solid Implant Contain either carbon fibres or aluminium oxide as reinforcing materials. manufactured as sponges with pores occupying about 70% of the volume. ePTFE-Coated Extended Pore sizes are in the hundreds of micrometers making Anatomical Chin these implants easy to carve into custom shapes and used in facial sizes. augmentation Initiates a significant inflammatory response that eventually subsides in a period of months.  Synthetic Implant Materials-Facial Solid Facial Implants : Potential Complications The problem of extrusion of solid synthetic facial implants (i.e. rejection) must be considered. Main surgical factors that may influence implant extrusion : Depth of soft tissue coverage Implant movement Infection associated with use of an implant Introduction of tension in the skin Coverage of the implant with poorly vascularised thin skin, movement of the implant, infection and closure of the wound containing the implant under tension frequently lead to implant extrusion. Mesh Materials A number of synthetic polymers are used in the form of an open mesh work of fibres including polyglycolic acid and polylactic acid. Mesh materials are used for any site requiring augmentation where small defects or contours exist such as the bridge of the nose, the chin, and the cheeks.  Synthetic Implant Material - Bone The partial replacement of bones, destroyed by cancer, injury, or surgery, remains an important medical problem. There are hundreds of thousands of operations to restore the integrity of damaged bone tissue annually throughout the world. Bone tissue possesses a natural ability to regenerate, but in case of large defects the natural ability is often insufficient for complete bone repair. That's why to repair damaged bone tissue, various types of implants are used. Materials used for bone implants must have a number of specific properties:  possess high mechanical properties  be biologically compatible with the host's body  ensure the complete replacement of the bone loss  initiate the processes of bone tissue regeneration  Synthetic Implant Material – Bone Example 1. ‘Hyperelastic Bone’ “HB can be implanted under the skin as a scaffold for new bone to grow on, or used to replace lost bone matter altogether. Though it hasn’t been tested in humans yet, early experiments on animals appear to have been successful, with "quite astounding" results, according to the researchers. Hydroxyapatite — a form of calcium found in bone and already used in reconstructive surgeries — is extremely brittle, but the researchers mixed it with a polymer to add flexibility. They then 3D print bone graft from this new, promising material and tested it in various experiments. It is also highly porous and absorbent — which is crucial for bone graft material to encourage the growth of blood vessels into the surgery area.” https://www.sciencemag.org/news/2016/09/print-demand-bone-could-quickly-mend-major- injuries http://stm.sciencemag.org/content/8/358/358ra127  Synthetic Implant Material - Bone Example 2. ‘Iron Polymer’ Ult r a -h ig h -m o le c u la r -w e ig h t p o ly e t h y le n e is su it a b le fo r t h e c rit e ria d e sc rib e d. E.g. if w e t a lk a b o u t m e c h a n ic a l p ro p e rt ie s in t e rm s o f st re n g t h o r se lf-w e ig h t , p ro d u c t s fro m UHMW P E h a ve m e a su re m e n t s t h a t e xc e e d st e e l. Ho w e ve r, t h e e xt re m e ly h ig h m o le c u la r w e ig h t o f p o lym e r p re vio u sly d id n ’t a llo w fo r t h e u se o f t ra d it io n a l m e t h o d s o f c re a t in g a p o ro u s st ru c t u re i.e. c a n c e llo u s b o n e (t yp ic a lly t h e y a re c re a t e d b y fo a m in g ). Th e p ro b le m w a s so lve d w it h t h e h e lp o f a so lid -p h a se m ixin g m e t h o d , t h e rm o p re ssu re , a n d rin sin g t h e m a t e ria ls in su b c rit ic a l w a t e r. W it h s u c h in g e n u it y, a g r o u p o f Ru s s ia n s c ie n t is t s s o lve d t h e p r o b le m o f s im u la t in g t h e c o m p le x s t ru c t u re o f c a n c e llo u s b o n e s fo r t h e fir s t t im e , a n d c r e a t e d t h e m u lt i-la y e r UHMW P E s c a ffo ld s w it h a s o lid e xt e r io r a n d p o r o u s in n e r la y e r.  Synthetic Implant Material - Bone Example 2. ‘Iron Polymer’ "Our scaffold consists of two layers, which are connected to each other very firmly. The first layer is solid - it simulates the cortical bone to ensure the mechanical strength. The inner layer has pores of a certain size, that's why it can be colonized by cells from the recipient to accelerate the fusion with surrounding tissues and to provide a strong fixation of the implant in the defective area“ - Fedor Senatov, head of the project at the NUST MISIS Center of Composite Materials. Th e st ru c t u re o f im p la n t s c re a t e d fro m Ult ra -h ig h m o le c u la r w e ig h t p o lye t h yle n e is id e n t ic a l t o b o n e ’s st ru c t u re (P RNe w sFo t o /NUST MISIS) Learning Points 1. Tissue Implants - Background 2. Biological Implants ◦ Autografts ◦ Homografts 3. Synthetic Implants – injectables, solids, meshes 4. Case Study – Tissue/Vessel Mimicking Materials  Case Study - Tissue Mimicking or Vessel Mimicking Materials Tissue mimicking and vessel mimicking materials:  replicate the behaviour of the tissues, quality assurance/performance testing  gain a better understanding of how the tissue/vessel/organ behave,  thus predict the occurrence of disease at an earlier stage. Doppler ultrasound Blood Flow in the Renal Artery Doppler ultrasound  The Doppler frequency, fD (i.e. the difference between the transmitted and received frequencies, Doppler Shift) may be calculated using: 2 fovCosθ fD = c Where fo is the frequency of the transmitted signal (same as fe), v is the velocity of the moving blood cells and c is the speed of sound of the medium (1540 m/s). If the Doppler frequency shift can be measured then an estimate of the velocity may be calculated, if θ is known.  Doppler ultrasound Doppler imaging looks at carotid artery  This is also a carotid artery. Get image and trace of blood flow  The flow is not all in the same direction. It is turbulent, like rapids in a river. This is a healthy artery. The flow is smooth and all in  This is usually due to a build-up of fatty deposits the same direction, like water in a large, slow river in the artery Early detection of cardiovascular disease by thickening of artery wall Photograph of the mould used for producing the vessel mimicking material for the walled anatomically realistic renal artery flow phantoms.  Aside: Freeze-thaw action for increased mechanical stiffness explained During the freezing of the PVA solution, ice created in the amorphous region induces the growth of polymer crystallinites which act as physical crosslinking points between PVA chains, and thus produces the water-insoluble hydrogel. The mechanical properties of PVA hydrogel are dependent on polymer concentration, freezing time and temperature, and the number of freezing–thawing cycles Kim et al. “Creating stiffness gradient polyvinyl alcohol hydrogel using a simple gradual freezing–thawing method to investigate stem cell differentiation behaviors”, Biomaterials 40, 51-60 (2015)  𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝑐𝑐 = 𝜌𝜌 (𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑)  Fig. 8 (inset) Fig. 7. plot of experimental stress vs time fitted with the Maxwell model  Fig. 7. plot of experimental stress vs time fitted with the Maxwell model Experimental data fitted with: Fig. 8. Variation of the relaxation time parameter, τ, derived from a Maxwell Model, with increasing freeze-thaw cycles. Next week CA2 – in class test 8 short questions Example CA test on Brightspace + solutions to the L9 handout