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Flashcards by Bhavi Mistry, updated more than 1 year ago
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Created by Bhavi Mistry
almost 9 years ago
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| Question | Answer |
| The need for implants | Ageing population Increased surgeon confidence Increased patient acceptance Governmental regulatory support Improvements in surgical skill Improvements in biomaterials |
| Implant limitations | Non living: natural tissue can repair itself, implants cannot Failure: post op morbidity/mortality Mis-match in biochemical/mechanical properties: leads to devential failure |
| Biocompatibility | Shift in materials towards becoming more bioreactive, previously they were mainly bio inert |
| Classes of biomaterials | Bio-inert: fibrous encapsulation Bio-degradeable: degradeable into natural monomers Bio-reactive: interaction with body tissue (positive stimulatory signals, e.g. to induce growth) |
| Bioreactivity spectrum: relative bioreactivity of the course of implantation time | Type 1: nearly inert Type 2: porous Type 3: bioactive Type 4: Resorbable |
| Main causes of hip implant failure | Lack of implant remodeling Stress shielding Contact forces at hip cause fractures Shear stress: load not transmitted to bone Wear between ball and socket from the implant: osteolysis and bone loss |
| Stress shielding | Stress shielding refers to the reduction in bone density (osteopenia) as a result of removal of normal stress from the bone by an implant (for instance, the femoral component of a hip prosthesis). |
| Osteochondral regeneration | Drill into bone to release new stem cells to release cartilage stem cells; however, these have the tendency to differentiate into hyaline cartilage as opposed to hyaline cartilage |
| THR types | Charnley: Co-Cr fem implant. PMMA cemented Charnley type (low friction): THA with metallic femoral component and UHMWPE cup |
| PMMA: how does it work? | 2: 1 powder to liquid mix Creates a pliable putty that can be moulded mis-noma: doesn't actually act as cement Grouting to facilitate implant fixation by wedging |
| Problems with PMMA | Difficult revision Shrinkage: loosening Osteonecrosis (at end polymerisation) Brittle cement particles can fall into the gap caused on shrinking: wear particle formation --> osteolysis (resorption) |
| Bioactive coatings | e.g. HA plasma spray onto metal component of implants to allow OB and OCl remodelling to integrate easier revision But runs out Takes long to load bear |
| Effect of loading environment | High stress concentration/stress shielding: bone resorption around the implant |
| Aseptic loosening | failure of joint prosthesis withouht presence of mechanical cause or infection: associated with osteolysis/inflammatory response |
| Wear | there ought to be minimum friction between articular surfaces which leads to reduced wear particle formation wear particles: l |
| Wear particles: the problem | largest proportion of failed orthopaedic implants Occurs at articulating surfaces and at bone-implant interfaces: leads to osteolysis due to immune reaction leading to failure |
| Solution to wear: UHMWPE | Reduce implant stiffness to reduce friction High impact strength, bio inert good cyclical fatigue resistance |
| Problems with UHMPWE | Poor wear resistance Sterilisation reduces properties difficult to process into shape |
| Solutions | MIS Metal on metal Ceramic on ceramic |
| Metal-metal: advantages and disadvantages | Biometals: stainles steel/titanium and cobalt alloys (BHAM hip) Advantages: strength, lower wear rate than UHMWPE Disadvantages: Metal wear particles are more toxic |
| Ceramic on ceramic | Use: femoral head in load bearing in hip prosthesis for younger patients advantages: Very strong, corrosion resistance, good biocompatibility Disadvantages: Squeaking, shatters if there is a crack, heavier |
| Transplants | Autograft: donor site injury, limited tissue availability Allograft: Immunorejection, lack of donors Xenograft: immune rejection and disease risk |
| Regeneration over reabsorption: Resorbable bioceramics - degrade over time and be replaced by natural host tissue ( better than autografts?) | Issues: Matching rate of degradation to rate of replacement and strength maintenance of interfaces during bioglass degradation |
| Bioglass | Combines with bone faster than HA, contains ions that stimulate osteogenesis (Novabone - sensodyne, perioglass) |
| 3D printing of scaffolds | Implanting degradeable scaffold. NB regulatory approval required |
| Summary: J Jones lecture | THRs: revolutionary, but limited survival + QoL improvement, but to a limited degree Movement towards regeneration over replacement |
| What is a scaffold? | 3D porous temporary template that substitutes the damage tissue and guides the growth of healthy tissue while it is bioresorbed Can be used to trigger and prmote tissue regeneration |
| What surgeons want - not always what developers make | simple, easy to use, safe Putty/pliability to adapt to body defect Load bearing (ortho) |
| Ideal scaffold properties for regeneration | Template for tissue growth Porous network (vascularisation, tissue ingrowth, nutrient delivery) Bond to host tissue without scar formation reabsorb at rate of repair Signals to cells to grow |
| Mechanical properties of a scaffold for bone regeneration | load bearing: share mechanical load with host bone Maintain this during degredation and remodelling Not too ridgid, but not collapsable Strong enough to be handled by surgeons in the operating theatre |
| Mechanical properties vs biodegradation: scaffolds | Mechanical properties must be maintained during degradation. This should be matched to the rate of growth of the new tissue |
| Interconnected porosity | vascularisation, cell migration, nutrients and waste diffusion 500 micrometer pores with 100 micrometer interconnection is ideal IF you change one factor, the others will be affected. E.g. increased porosity will weaken mechanical strength |
| Cartilage structure | Chrondrocytes in lacunae. Cartilage stiffness increases from apical surface to cancellous bone. therefore materials are needed to match the gradient of the stiffness: e.g. Triphasic scaffolds |
| Challenges with osteochondral scaffolds | Mechanical propeties: gradient of stiffness required (as with normal cartilage structure) Challenges: matching it to this, and ensuring bone fixation Challenge: rate of formation of tissue to rate of degradation of scaffold is different in each individual - difficult to standardise and mass produce Cartilage: avascular: smaller porosity |
| Biomaterials generations | 1st: Allograft based, metals, bioceramics, polymers 2nd: Composites (e.g HA sprayed onto metal) 3rd: Hybrids (shift towards these) |
| Bioceramics properties | Osteoconductive: cells do note react to it Bio and non-bioresorbable Osteoinductive: ion release that stimulate tissue generation Osteoinductive AND resorbable: Bioactive glasses |
| Polymers | Natural: good biocompatibility, but poor reproducability and procesability (Collagen, gelatin, chitosan) Synthetic: Good reproducability and biodegradability |
| Manufacturing techniques | Foaming (like a meringue): application to ceramics and hybrid metals but not mechanically adequate, not reproducable easily, Electrospinning (candyfloss): not weight bearing, but can be used as bone filler 3D printings and robocasting: high specificity and reproducablity, but requires optimising for each technique |
| Composite | C ombines the advantages of polymers and bioceramics: e.g. HA on metal interface. Inorganic coating of a polymeric skeleton Problems: cell-material interaction and matching degradation rate of matrix and dispersed phase |
| Hybrids | Combine best properties of organic and inorganic compounds Molecules are bonded at the molecular level: they cannot be distinguished above the nanoscale Problem: matching degradation rates (can be confounded by metabolism and enzymes, etc) |
| Tissue engineering | Applies principles of life sciences to development of biological substitues that restore, maintain/improve tissue function |
| Strategies for tissue engineering | Isolated cell or cell substitutes: avoids surgery, but can fail to maintain function/can be rejected Tissue-inducing substances: e.g. synthesis of growth factors to facilitate cell growth (expensive) Cells placed on or within matrices: allows permeation of nutrients and wastes |
| The need for tissue engineering | Degenerative diseases: OA Severe trauma: challenging natural repair e.g. severe burns - may not be enough tissue to procure grafts Organ transplant: limited availability (the future) |
| Current treatments for OA | Marrow stimulation Chondral Grafts ACI TKR (late stage): implant failure 15-20 yrs |
| Whole organ transplantation problems | Long waiting list Donor shortages Immunological suitability IRI: EVLP strategy to preserve, but still has limitations (INSPIRES) |
| Goal of tissue engineering | create synthetic tissue to take over function of the failing one Treat complex diseases |
| Three main pillars of tissue engineering | 1) cells 2) Scaffolds 3) signalling molecules |
| ACI limitations | 2 stage procedure: cells harvested then expanded in vivo, then re implanted to fill the defect (involves periosteal stripping to patch over the graft). NOT recommended by NICE multiple operatrions, cost and labour intesntive Problems with cell culture: They need to be grown in 3D or they lose ability to resist compression and damage |
| Adult stem cells | Differentiate, but are more specialised then embryonal stem cells Post-nnatal stem cells have extended self renewable capacity and are multipotent |
| MSCs | From mesenchymal layer in embryology, are multipotent. Have the tendency to develop specifically into cartilage, heart, neural tissues etc.. Complications: e.g growing nose on back All MSCs are |
| Tissue specific stem cells | E.g HSCs More specialised than embryonal stem cells, potential solution (e.g. problems in hepatocyte transplantation, not much research into use for cartilage) More research with HSCs |
| Tissue specific stem cells advantages and disadvantages | Extended self-renewal capacity Multipotent Paracrine signalling potential BUT Heterogeneous population Unreliable results Issue in cartilage repair high variability in chondrogenic differentiation generation of mechanically inferior fibrocartilage |
| Pluripotent stem cells | Human induced: gene splicing into adult stem cells to convert them back, overcomes ethical considerations, but laborious, take six weeks to develop Embryonic: harvested from the embryo. Indefinite cell renewal, but difficulty to manipulate |
| Scaffold in tissue engineering | provides structural support, template for cell attachment and matrix formation Architecture influences how cells behave (e.g. pore size, distribution, geometry etc) |
| Natural matieral scaffolds: collagen, fibrin, hyaluronon | Usually biocompatible/biodegradeable Natural materials: biocompatible, but dificult to process and often have poor mechanical properties |
| Synthetic matierals: e.g. polymers, ceramics, bioactive glass | Advantages: easier processing, reliable outcome, tailorable properties Disadvantages: Biocompatibility, carefully designed degradation |
| The importance of scaffold mechanical properties | Scaffold needs to match the mechanical properties of the native tissues in order to effectively carry out function while regeneration occurs. Matched degradation rate ensures that the scaffold does not degrade until the bone is able to take over load bearing Mechanical incompatibility can lead to stress shielding and osteolysis |
| Growth factors and signalling factors | Singalling factors can be environmental, but other types exist: cell-cell/cell-matrix etc Growth factors: instruct cell behaviour and guide tissue proliferation e.g. TGF- B to prevent cartilage mineralisation |
| Mechanical stimulation | Bioreactors; mimic in vivo conditions in a closely controlled environment |
| Environmental factors | Cartilage: Hypoxia essential forchondrocyte differentiation and survival: controls ECM synthesis Bone: HIF 1 alpha accelerates bone regeneration via VEGF for osteogenesis and enchondral ossification |
| Cartilage regeneration: Composition | Firm elastic CT between bones rib cages etc. Provides biomechanical support Hyaline: T2 collagen, GAGs and water |
| Cartilage functions | Support and shape Shock absorption Lubricant in joints |
| Composition of cartilage | Chondrocytes in lacunae: vital for regeneration. Migrate up though cartilage zones, but get older as we do therefore we are unable to maintain it Contain: Collagen, elastin, GAGAs, Calcium and H2O Avascular, a neural, low metabolic rate |
| Role of ECM in defining mechanical properties of cartilage | Mechanical behaviour of articular cartilage: sponge like Increased charge density (from GAGs) when compressed. Water squeezed out of cartilage |
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