Implantable Devices

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This section covers prosthetic heart valves, artificial and biological vascular grafts, stents, catheters and cannulas, cardiac pacemakers, inferior vena cava filters, the intra-aortic balloon pump and ventricular assist devices.

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Prosthetic Heart Valves A prosthetic valve replaces a diseased native valve (most often the aortic or mitral) and must open with minimal pressure gradient, close completely without regurgitation, resist about 40 million cycles a year without fatigue, and avoid causing thrombosis or haemolysis.

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Mechanical valve Bioprosthetic (tissue) valve Materials Pyrolytic carbon leaflets and housing, titanium or Co-Cr stiffening ring, Dacron or PTFE sewing ring Glutaraldehyde-fixed porcine aortic valve or bovine pericardium on a metal or polymer stent with a fabric sewing ring; or a stentless/homograft valve Durability Excellent — 20-30 years or more Limited — 10-15 years, less in young patients Anticoagulatio n Lifelong warfarin, INR monitored Not usually required beyond the early months Main failure mode Thrombosis, thromboembolism, bleeding from anticoagulation, pannus ingrowth, haemolysis Structural valve deterioration by calcification and leaflet tearing Typical patient Younger patient able to manage anticoagulation Older patient, or one who cannot take anticoagulants (including women planning pregnancy) Other Audible click;

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MRI generally safe with modern materials Quiet, more physiological flow • Generations of mechanical valve: the caged ball (Starr-Edwards, 1960) — durable but with high profile, turbulent flow and haemolysis; the tilting disc (Björk-Shiley, Medtronic-Hall) — a single disc giving better but asymmetric flow; and the modern bileaflet (St Jude and successors) — two semicircular pyrolytic carbon leaflets giving the most central, least obstructive flow and the lowest thrombogenicity, now the standard design. • Bioprosthetic calcification is the central failure mechanism: glutaraldehyde fixation leaves non-viable cells whose membrane phospholipids and residual aldehyde nucleate calcium phosphate.

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Anti-calcification treatments (detergents, ethanol, α-amino oleic acid) and alternative crosslinkers are used to delay it. • TAVI/TAVR — transcatheter aortic valve implantation — delivers a bioprosthesis crimped on a balloon or self-expanding nitinol frame through a catheter, avoiding open surgery; it has transformed treatment for high-risk and elderly patients. • Haemodynamic design requirements: minimal transvalvular gradient and effective orifice area as large as possible, no stagnation or recirculation zones (which cause thrombus), and shear stress below the threshold for haemolysis and platelet activation — the direct application of 1.6 and 2.6.

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Vascular Grafts • Artificial (synthetic) grafts:

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Dacron (PET), knitted (more porous, needs pre-clotting or albumin/collagen sealing, better tissue incorporation) or woven (tighter, less bleeding), used for the aorta and large arteries; and ePTFE, whose node-and-fibril structure gives controlled porosity, used for medium-sized vessels and dialysis access.

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Both work well at large diameter, where flow is fast. • The small-diameter problem: below about 6 mm synthetic grafts fail, because low flow and a thrombogenic surface cause early thrombosis, and compliance mismatch between a stiff graft and the elastic artery creates disturbed flow at the anastomosis, provoking intimal hyperplasia that narrows and occludes the graft.

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For coronary and below-knee bypass, the autologous saphenous vein or internal mammary artery remains the gold standard. • Biological grafts: autograft (the patient's own vein or artery — no immune response, best patency), allograft (human donor, cryopreserved), xenograft (bovine, glutaraldehyde-treated) and decellularised matrix scaffolds. • Improvement strategies: heparin bonding, endothelial cell seeding, compliance-matched elastomeric grafts, electrospun and tissue-engineered vessels, and drug-eluting surfaces. • Requirements of a graft: patency, strength and burst resistance, compliance matching, suturability and resistance to needle-hole bleeding, kink and compression resistance, no dilatation over time, infection resistance and sterilisability.

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Stents, Catheters and Cannulas • Stents are expandable tubular scaffolds that hold a vessel or duct open.

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Balloon-expandable stents (usually 316L stainless steel or Co-Cr) are crimped on a balloon and plastically deformed in place — precise, used in the coronaries; self-expanding stents (nitinol) recover their shape by superelasticity and are used where external compression is possible, as in the carotid and peripheral arteries. • Evolution: bare-metal stents solved the elastic recoil and dissection of plain angioplasty, but suffered in-stent restenosis from neointimal hyperplasia; drug-eluting stents carry an antiproliferative drug (sirolimus, everolimus, paclitaxel) in a polymer coating, which greatly reduced restenosis but delayed endothelialisation and introduced a risk of late stent thrombosis, requiring prolonged dual antiplatelet therapy; bioresorbable scaffolds (PLLA or magnesium) were developed to disappear once healing is complete.

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Other stents: ureteric, biliary, oesophageal, tracheal. • Design requirements for a stent: low crossing profile and flexibility for delivery, sufficient radial strength against recoil, minimal foreshortening and recoil, good radiopacity, adequate scaffolding with a low metal-to-artery ratio, fatigue resistance over 400 million cardiac cycles, and haemocompatibility. • Catheters and cannulas: a catheter is a flexible tube introduced into a vessel or cavity to deliver or drain fluid or to carry instruments; a cannula is a (usually shorter, stiffer) tube placed to provide access, typically over a needle or trocar.

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Materials are polyurethane, silicone, PVC, PTFE and nylon, chosen for flexibility, kink resistance and haemocompatibility, and often radiopaque (barium or tungsten filled), hydrophilic-coated for lubricity, and heparin- or antimicrobial-coated.

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Types include peripheral and central venous catheters, PICC lines, Swan-Ganz (pulmonary artery) catheters, angiographic and balloon catheters, and the cannulas of cardiopulmonary bypass and ECMO. • Principal complications: catheter-related bloodstream infection from biofilm (2.6), thrombosis, mechanical damage and breakage, and extravasation — which is why insertion technique, dwell time and antimicrobial coatings matter so much.

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Cardiac Pacemakers • A pacemaker delivers timed electrical stimuli to the myocardium when the natural conduction system (1.4) fails — in symptomatic bradycardia, sick sinus syndrome and atrioventricular block.

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It comprises a hermetically sealed titanium can housing the lithium-iodine battery (typically 7-12 years) and circuitry, and one or more leads with silicone or polyurethane insulation and platinum-iridium electrodes, often steroid-eluting to suppress the local inflammatory response and keep the stimulation threshold low.

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Fixation is active (screw-in helix) or passive (tines). • Key parameters: threshold (the minimum energy that reliably captures the myocardium), output (amplitude and pulse width, typically 2-5 V and 0.4-0.5 ms), sensitivity (the smallest intracardiac signal detected), refractory periods and blanking, and rate limits. • The NBG code is examined regularly:

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I = chamber paced, II = chamber sensed, III = response to sensing, IV = rate modulation, V = multisite pacing, with A = atrium, V = ventricle, D = dual, O = none, I = inhibited, T = triggered, R = rate responsive.

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Hence VVI = paces the ventricle, senses the ventricle, inhibited by a sensed beat;

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DDD = paces and senses both chambers with both inhibition and triggering, preserving AV synchrony;

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DDDR adds rate response driven by an activity or minute-ventilation sensor. • Related devices: the implantable cardioverter-defibrillator (ICD), which detects ventricular tachycardia or fibrillation and delivers anti-tachycardia pacing or a shock; cardiac resynchronisation therapy (CRT, biventricular pacing) for heart failure with dyssynchrony; and leadless pacemakers implanted entirely within the right ventricle. • Problems: lead fracture and insulation failure (the commonest hardware failures), dislodgement, rising threshold from fibrosis, infection of the pocket, electromagnetic interference, and MRI compatibility — modern systems are labelled MR-conditional.

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Inferior Vena Cava Filters, IABP and Ventricular Assist Devices • Inferior vena cava filter: a conical or umbrella-shaped nitinol or stainless steel device placed percutaneously in the infrarenal IVC to trap emboli travelling from the leg veins to the lungs.

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It is indicated when anticoagulation has failed or is contraindicated in a patient with deep vein thrombosis or pulmonary embolism.

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It prevents pulmonary embolism but does not treat the clot, and it must allow blood to pass freely while catching clots.

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Complications include filter thrombosis and IVC occlusion, migration, penetration of the caval wall, fracture and difficulty of retrieval — hence the preference for retrievable filters removed once the risk period has passed. • Intra-aortic balloon pump (IABP): a polyurethane balloon (30-50 mL) on a catheter placed in the descending thoracic aorta just distal to the left subclavian artery, driven with helium (chosen for its low density, allowing very rapid shuttling) and timed from the ECG or arterial pressure trace.

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It works by counterpulsation: it inflates at the dicrotic notch (the onset of diastole, as the aortic valve closes), raising diastolic pressure and increasing coronary perfusion, and deflates just before systole, lowering aortic end-diastolic pressure and therefore afterload and myocardial oxygen demand.

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The result is improved oxygen supply and reduced demand — used in cardiogenic shock, unstable angina and to wean from bypass.

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It requires some residual cardiac function and a reasonably regular rhythm, and is contraindicated in aortic regurgitation and aortic dissection. • Ventricular assist device (VAD): a mechanical pump that takes blood from a ventricle and returns it to the aorta (LVAD) or pulmonary artery (RVAD), or both (BiVAD).

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Indications are described as a bridge to transplant, bridge to recovery, bridge to decision, or destination therapy in patients who are not transplant candidates.

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The first generation was pulsatile and displacement-based; modern devices are continuous-flow rotary pumps — axial (HeartMate II) or centrifugal with magnetic or hydrodynamic bearings (HeartWare, HeartMate 3) — which are smaller, more durable and more energy-efficient, at the cost of reduced or absent arterial pulsatility. • VAD engineering constraints bring together the whole chapter: the blood path must avoid stagnation (thrombosis) and excessive shear (haemolysis, platelet activation and acquired von Willebrand syndrome); surfaces are titanium, sintered titanium microspheres or textured surfaces to stabilise a pseudo-neointima; a percutaneous driveline is the commonest site of infection, which is why transcutaneous energy transfer is pursued; and patients require anticoagulation and antiplatelet therapy.

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The total artificial heart replaces both ventricles entirely.

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This section covers the biomaterials used in orthopaedic implants, total hip replacement and total knee replacement, together with fixation methods and the modes of failure.

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Biomaterials Used in Orthopaedic Implants Material Role in orthopaedics 316L stainless steel Temporary internal fixation — plates, screws, intramedullary nails, wires, external fixator components Co-Cr-Mo alloy Femoral heads, knee femoral components, stems — chosen for its wear resistance Ti-6Al-4V and CP titanium Femoral stems, acetabular shells, spinal instrumentation, plates — chosen for lower modulus, corrosion resistance and osseointegration; not used as a bearing surface because it wears and galls badly UHMWPE The bearing surface — acetabular liners, tibial inserts, patellar components; highly crosslinked and vitamin-E stabilised grades reduce wear Alumina and zirconia ceramics Femoral heads and liners for ceramic-on-ceramic or ceramic-on-polyethylene bearings — lowest wear, but brittle PMMA bone cement Grouting agent for cemented fixation; may be loaded with antibiotic (gentamicin) or with barium sulphate for radiopacity Hydroxyapatite coating Plasma-sprayed on stems and cups to promote bone ongrowth in cementless fixation Porous metals (sintered beads, fibre mesh, porous tantalum) Surface for bone ingrowth in cementless components PEEK and carbon-fibre composites Spinal cages and radiolucent plates, with a modulus nearer to bone Resorbable polymers (PLA, PGA, PLGA) and magnesium Pins, screws, suture anchors and interference screws that need not be removed • Design requirements: strength and fatigue resistance for millions of gait cycles; a modulus as close to bone as practicable to limit stress shielding; excellent wear resistance at the bearing; corrosion resistance and low ion release; osseointegration or reliable cement fixation; and the ability to be sterilised without degradation.

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Total Hip Replacement (THR / THA) • Indications: pain and disability from osteoarthritis, rheumatoid arthritis, avascular necrosis, or fracture of the femoral neck in the elderly. • Components: the femoral stem (Ti alloy or Co-Cr) inserted into the medullary canal; the femoral head (Co-Cr or ceramic, typically 28-36 mm) attached by a Morse taper; the acetabular shell (titanium, often porous-coated or HA-coated); and the liner (UHMWPE, ceramic or metal).

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A hemiarthroplasty replaces only the femoral side; resurfacing caps the femoral head. • Bearing couples: metal-on-polyethylene (the long-standing standard, cheapest, but generates polyethylene wear debris); ceramic-on-polyethylene (lower wear); ceramic-on-ceramic (the lowest wear of all, but risk of fracture and of audible squeaking); and metal-on-metal (very low volumetric wear but produces enormous numbers of nanometre particles and cobalt and chromium ions, causing adverse local tissue reaction, pseudotumours and metallosis — which is why large-head metal-on-metal designs were largely withdrawn). • Fixation: cemented — PMMA fills the gap and interlocks mechanically with cancellous bone, giving immediate stability and suiting older patients with poor bone; or cementless (biological) — a press-fit, porous- or HA-coated surface into which bone grows over weeks, preferred in younger patients with good bone, and needing initial mechanical stability with micromotion below about 50 μm for bone rather than fibrous tissue to form.

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Hybrid fixation combines the two. • Head size trade-off: a larger head increases the range of motion and stability against dislocation and raises the jump distance, but increases the sliding distance and therefore volumetric wear in a polyethylene bearing. • Complications: aseptic loosening secondary to wear-debris-induced osteolysis — historically the commonest cause of late failure; infection (biofilm, often requiring two-stage revision with an antibiotic spacer); dislocation; periprosthetic fracture; leg-length discrepancy; stress shielding with proximal femoral bone loss; taper fretting corrosion in modular designs; and heterotopic ossification.

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Total Knee Replacement (TKR / TKA) • The knee is mechanically more demanding than the hip because it is not a simple ball-and-socket: normal motion combines flexion-extension with rolling, sliding and axial rotation (the screw-home mechanism), and stability depends on ligaments rather than on bony containment. • Components: a femoral component (Co-Cr, with condylar curves), a tibial component (titanium or Co-Cr tray with a UHMWPE insert, or an all-polyethylene tibia), and an optional patellar button (UHMWPE).

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The articulation is therefore metal or ceramic on polyethylene. • Design variants: cruciate-retaining (preserves the posterior cruciate ligament, more natural kinematics) versus posterior-stabilised (PCL sacrificed, a cam-and-post mechanism substituting for it); fixed-bearing versus mobile-bearing (rotating platform), which increases conformity without raising constraint; unicompartmental replacement for single-compartment disease; and constrained or hinged designs where ligaments are deficient. • The conformity dilemma: a highly conforming articulation spreads contact over a larger area, lowering contact stress and polyethylene wear, but it transmits more constraint force to the fixation interface, promoting loosening; a less conforming design allows natural motion but concentrates stress and wears faster.

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Every knee design is a compromise between these. • Alignment is critical: the components must restore the mechanical axis, and malalignment of only a few degrees markedly increases edge loading, wear and loosening — which is why computer navigation, patient-specific instruments and robotic assistance have been introduced. • Failure modes: polyethylene wear and delamination (fatigue-driven, since contact stresses are higher and less conforming than in the hip), aseptic loosening, infection, instability and malalignment, stiffness and arthrofibrosis, patellar complications, and periprosthetic fracture.

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This section covers the materials used in urological implants, urethral catheters and their design, ureteral and urethral stents, and the characteristic complications of encrustation and infection.

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Materials Used in Urology Implants • The urinary tract is a uniquely hostile environment for a device: the device is continuously bathed in urine, which is supersaturated with calcium and magnesium salts and varies in pH; it is open to the exterior and therefore to bacterial colonisation; and it must remain in a soft, mobile, contractile conduit without causing trauma.

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The two governing problems are therefore encrustation and infection. • Requirements: biocompatibility with urothelium, resistance to encrustation, resistance to bacterial adhesion and biofilm, appropriate flexibility with kink and compression resistance, low friction for insertion, chemical stability in urine, radiopacity, and sterilisability.

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Material Properties and use Latex Cheap and very flexible, but encrusts rapidly, causes urethral irritation and carries a latex allergy risk; now usually coated or replaced Silicone (PDMS) The standard for long-term catheters — highly biocompatible, soft, very resistant to encrustation, thin-walled so the lumen is larger for a given size; more expensive and less strong Hydrogel-coated and silicone-coated latex Hydrophilic coating reduces friction and bacterial adhesion while retaining the cheapness of latex Polyurethane Strong, thin-walled and stiff at room temperature but softening at body temperature — the usual material for ureteral stents; more encrustation-prone than silicone PVC and PTFE Intermittent catheters and sheaths;

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PTFE-coated latex reduces irritation Metals — nitinol, stainless steel Permanent or temporary metallic urethral/prostatic stents and ureteral stents that resist external compression by tumour Coatings Silver alloy (antibacterial), nitrofurazone and antibiotic coatings, heparin (reduces encrustation), hydrophilic and phosphorylcholine coatings Urethral Catheters • A urethral catheter drains the bladder through the urethra.

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The common types are the Foley (indwelling, self-retaining) catheter with an inflatable balloon near the tip, the Nelaton or intermittent (straight, no balloon) catheter used for clean intermittent self-catheterisation, the Coudé catheter with an angled tip to negotiate an enlarged prostate, and three-way catheters with an extra channel for continuous bladder irrigation.

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A suprapubic catheter avoids the urethra altogether. • Design of the Foley catheter: a balloon (typically 5-10 mL, or 30 mL for haemostasis after prostate surgery) inflated with sterile water, not saline (which can crystallise and block the inflation channel) and not air (which floats); drainage eyes near the tip; and two or three lumens.

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Size is given in the French (Charrière) gauge, where 1 Fr = 1/3 mm of outer diameter — so a 16 Fr catheter is 5.33 mm across; the smallest catheter that drains adequately should be used. • Indications: acute or chronic urinary retention, accurate measurement of output in the critically ill, perioperative bladder drainage, irrigation for clot retention, and management of neurogenic bladder (1.5). • Complications: catheter-associated urinary tract infection (CAUTI) — the commonest healthcare-associated infection, with the risk rising by roughly 3-7 % per day of catheterisation; urethral trauma, stricture and false passage; balloon-related injury if inflated in the urethra; bladder spasm; encrustation and blockage; and catheter-related bladder discomfort. • Prevention of CAUTI is largely a matter of discipline rather than materials: insert only when genuinely indicated, use aseptic technique, maintain a closed drainage system with the bag below bladder level and free of kinks, avoid routine changes and irrigation, and remove the catheter as early as possible — the single most effective measure.

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Urological Stents • Ureteral (double-J or JJ) stent: a soft polyurethane or silicone tube with a curled pigtail at each end — one in the renal pelvis and one in the bladder — which prevents migration in either direction.

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Its purpose is to maintain urine drainage from kidney to bladder after ureteroscopy or stone surgery, across a stricture or tumour compression, during pregnancy-related obstruction, or to protect a ureteric anastomosis.

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Stents are radiopaque and carry side holes along their length. • Stent-related problems: flank and suprapubic pain, frequency, urgency and haematuria (the stent symptom complex, present in the majority of patients), vesico-ureteric reflux up the stent, migration, encrustation and fragmentation, and infection.

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A forgotten stent left in place for months encrusts and may become impossible to remove endoscopically — which is why every stent must be recorded and removed or exchanged on schedule (typically within 3-6 months, and much sooner for some designs). • Metallic and covered ureteral stents resist external compression by tumour and last longer, and biodegradable stents are being developed to abolish the removal problem. • Urethral and prostatic stents: expandable metal or polymer devices placed in the prostatic urethra to relieve bladder outflow obstruction in men unfit for surgery — either temporary (removable) or permanent (epithelialising).

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Encrustation, migration and irritative symptoms limit their use. • Other urological implants worth naming: the artificial urinary sphincter (a silicone inflatable cuff, pressure-regulating balloon and scrotal pump for severe incontinence), penile prostheses, sacral neuromodulation devices, synthetic mid-urethral slings and pelvic meshes (polypropylene — the subject of major safety controversy and regulatory restriction because of erosion and chronic pain), and ureteral or bladder tissue-engineered constructs.

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Encrustation and Biofilm: the Central Problem • Encrustation is the deposition of crystalline mineral on the device surface.

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Its classic mechanism is urease-driven: urease-producing bacteria, above all Proteus mirabilis (also Klebsiella, Providencia and Pseudomonas), hydrolyse urea to ammonia, raising the urine pH.

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Above the nucleation pH the urine becomes supersaturated and struvite (magnesium ammonium phosphate) and carbonate apatite crystallise on the catheter or stent, blocking it and forming the nidus of infection stones. • Sequence on the device: conditioning film of urinary proteins within minutes → bacterial adhesion → biofilm with its polysaccharide matrix → urease activity and pH rise → crystal nucleation and growth → blockage.

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Biofilm confers the same antibiotic tolerance described in 2.6, so the infection cannot be cleared while the device remains. • Countermeasures: silicone rather than latex; hydrophilic, heparin, phosphorylcholine and diamond-like carbon coatings; silver alloy and nitrofurazone coatings; urease inhibitors and urinary acidification; adequate fluid intake; and, decisively, removal or timely exchange of the device.

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This section covers the materials used in plastic surgery, the types and procedures of breast implants, gels and fillers, skin implants and substitutes for burns, and craniomaxillofacial reconstruction.

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Materials Used in Plastic Surgery Implants Material Use Silicone elastomer and gel Breast implants, testicular and calf implants, chin and malar implants, tissue expanders — the dominant material ePTFE (Gore-Tex) Facial augmentation, nasal and chin implants, soft-tissue suspension — porous, allowing limited tissue ingrowth Porous polyethylene (Medpor) Orbital floor, ear, nasal and craniofacial reconstruction — the porosity (>100 μm) allows genuine tissue and vascular ingrowth and fixation Polypropylene and polyester mesh Abdominal wall and chest wall reconstruction Titanium and titanium mesh Craniofacial plates, screws and mesh; orbital floor repair; distraction devices PMMA and PEEK Custom cranioplasty implants, often patient-specific and CAD/CAM manufactured Hydroxyapatite and bioactive ceramics Bone void filling, orbital implants (porous HA integrates and allows motility) Resorbable polymers (PLLA, PGA, PLGA) Paediatric craniofacial plates and screws that disappear as the skull grows Collagen, hyaluronic acid, acellular dermal matrix Fillers, soft-tissue support, breast reconstruction slings, skin substitutes Autologous tissue Fat grafting, bone and cartilage grafts, flaps — the biological alternative to any implant Breast Implants • Indications: reconstruction after mastectomy for cancer, correction of congenital asymmetry or deformity, and cosmetic augmentation. • Construction: all modern implants have a silicone elastomer shell.

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The filler is either silicone gel — a softer, more natural feel, and modern cohesive ('gummy bear') gel holds its shape and does not migrate if the shell ruptures — or saline, which can be filled after insertion through a smaller incision and is harmlessly absorbed if it leaks, but feels less natural and may show rippling. • Shell surface: smooth or textured.

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Texturing was introduced to reduce capsular contracture and to stabilise anatomically shaped implants, but certain macrotextured designs have been associated with BIA-ALCL (breast implant-associated anaplastic large cell lymphoma), a rare T-cell lymphoma arising in the capsule, which has led to withdrawal of some products and to continued surveillance.

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Shape may be round or anatomical (teardrop). • Procedures: the implant is placed through an inframammary, periareolar, transaxillary or (rarely) transumbilical incision, into a subglandular, subfascial, submuscular (subpectoral) or dual-plane pocket; submuscular placement gives better upper-pole coverage and a lower rate of capsular contracture.

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Reconstruction may be immediate or delayed and is often two-stage, with a tissue expander gradually inflated through a port to stretch the skin envelope before exchange for the definitive implant; acellular dermal matrix is frequently used as an internal sling.

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Autologous reconstruction with a DIEP, TRAM or latissimus dorsi flap is the alternative. • Complications: capsular contracture — the commonest, a direct manifestation of the foreign body response of 2.6, in which the fibrous capsule thickens and contracts, graded by the Baker classification I to IV (I soft and natural;

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II slightly firm but not visible;

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III firm and visibly distorted;

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IV hard, distorted and painful); rupture (intracapsular or extracapsular, with silent rupture of gel implants detected by MRI or ultrasound); infection; haematoma and seroma; rippling; malposition and rotation; altered nipple sensation; interference with mammographic screening (needing Eklund displacement views); and BIA-ALCL.

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Implants are not lifetime devices and a proportion require revision.

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Gels and Fillers • Dermal fillers are injected to restore volume, efface wrinkles and contour the face — a minimally invasive alternative to implants or surgery. • Temporary (resorbable) fillers: hyaluronic acid is by far the commonest (Restylane, Juvederm and similar), typically crosslinked to prolong its life to 6-18 months; its outstanding advantage is that it is reversible — hyaluronidase dissolves it if the result is poor or a vascular occlusion occurs.

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Collagen (bovine, requiring skin testing, now largely superseded), calcium hydroxyapatite microspheres in a gel carrier (12-18 months, also stimulating collagen), poly-L-lactic acid (a collagen stimulator acting gradually over months) and autologous fat (abundant and natural, but with variable graft take). • Permanent fillers:

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PMMA microspheres in collagen, polyacrylamide gel and liquid silicone.

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These are now strongly discouraged for most uses, because complications are also permanent — nodules, granulomas, migration and chronic inflammation that cannot be reversed.

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Illegal industrial-grade silicone injection is a recognised cause of severe disfigurement. • Complications of filler injection: bruising, swelling, lumps and nodules, the Tyndall effect (a bluish discoloration when hyaluronic acid is placed too superficially), infection and biofilm, delayed hypersensitivity granuloma, and — the most feared — intravascular injection causing skin necrosis or blindness through retrograde embolisation into the ophthalmic artery.

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Knowledge of facial vascular anatomy, aspiration, slow low-pressure injection with a cannula and immediate availability of hyaluronidase are the standard safeguards. • Botulinum toxin, although not a filler, is used alongside them; as noted in 1.3 it blocks acetylcholine release at the neuromuscular junction, relaxing the muscles that create dynamic wrinkles.

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Skin Implants and Substitutes for Burns • Extensive burns destroy the skin's barrier and thermoregulatory functions, and when donor sites are inadequate a skin substitute is needed.

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Split-thickness autograft remains the gold standard but is limited by donor-site availability, which meshing and expansion only partly overcome. • Classification of skin substitutes: by duration (temporary dressing versus permanent replacement); by layer (epidermal, dermal or composite/bilayer); and by origin (biological — autograft, allograft, xenograft, amnion; or synthetic; or biosynthetic). • Temporary cover: cadaveric allograft (the biological standard for temporary cover), porcine xenograft, amniotic membrane, and synthetic dressings such as Biobrane (silicone film on a nylon mesh with porcine collagen). • Dermal substitutes:

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Integra — the classic device, a bilayer of bovine collagen and chondroitin-6-sulphate (the collagen-GAG copolymer of 2.2) with a silicone outer layer acting as a temporary epidermis; the matrix is vascularised and remodelled into neodermis over two to three weeks, after which the silicone is removed and a thin autograft applied.

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Others include Alloderm (acellular human dermis), Matriderm and Dermagraft (fibroblasts on a resorbable polyglactin mesh). • Cultured epidermal autograft (CEA, Epicel): the patient's own keratinocytes expanded in culture over about three weeks into sheets that can cover very large areas from a small biopsy — life-saving in massive burns, but fragile, expensive and slow, and without a dermis it gives poor durability, so it is often combined with a dermal substitute.

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Spray-on cultured cell suspensions (ReCell) shorten the delay. • Requirements of an ideal skin substitute: adherence, a moisture and bacterial barrier, no antigenicity or toxicity, rapid vascularisation, durability and flexibility, resistance to infection, long shelf life, cost-effectiveness and low scarring and contracture — no current product meets all of these, which is why this remains a major tissue-engineering target (3.6).

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Craniomaxillofacial Reconstruction • Indications: trauma (facial and skull fractures), tumour resection, congenital deformity (cleft lip and palate, craniosynostosis), infection and previous surgery — including cranioplasty to replace a skull defect after decompressive craniectomy. • Principles: restore the facial buttresses and three-dimensional skeletal framework, re-establish occlusion (the dental bite is the reference for every midface and mandible repair), protect the brain and orbital contents, and achieve symmetry and contour. • Fixation: the standard is rigid internal fixation with titanium miniplates and screws (titanium being chosen for its biocompatibility, osseointegration, low MRI artefact and the fact that it need not be removed).

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Resorbable PLLA/PGA plates are preferred in children, so that fixation does not restrain the growing skull and does not require a second operation. • Reconstruction of defects: autologous bone graft (calvarial split, rib, iliac crest, or a vascularised free fibula flap for the mandible) is the biological gold standard; alloplastic options are titanium mesh, porous polyethylene, PEEK and PMMA, and, for the skull vault, patient-specific implants designed from the CT scan by CAD and manufactured by additive manufacturing (3-D printing) — now standard practice and the clearest example in the chapter of engineering entering the operating theatre.

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Distraction osteogenesis gradually lengthens bone with an external or internal device, generating new bone and expanding the soft-tissue envelope. • Complications: infection and implant exposure (particularly where coverage is thin or the implant communicates with the sinuses), plate palpability and cold sensitivity, extrusion, malocclusion, resorption of bone grafts, growth disturbance in children, and imaging artefact.

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This section covers the types of ophthalmic implant — intraocular lenses, corneal implants and keratoprostheses, glaucoma drainage devices, orbital and scleral implants, and retinal prostheses — together with the materials used in ophthalmic surgery.

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Intraocular Lenses • The intraocular lens (IOL) replaces the natural crystalline lens removed in cataract surgery, which is by a wide margin the most commonly performed implant operation in the world and the leading cause of reversible blindness in Nepal and South Asia.

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The standard technique is phacoemulsification through a small incision with implantation of a foldable IOL in the capsular bag; in high-volume settings manual small-incision cataract surgery (MSICS) with a rigid or foldable lens is widely and effectively used. • Structure: a central optic (typically 5.5-6.0 mm) and two haptics that centre and fix the lens.

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Designs are one-piece or three-piece, and modern optics have a square posterior edge, which mechanically obstructs lens epithelial cell migration and markedly reduces posterior capsule opacification (PCO, 'after-cataract') — the commonest late complication, treated by Nd:YAG laser capsulotomy. • Materials:

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PMMA — the original material, discovered from the observation that Perspex splinters in the eyes of wartime pilots were well tolerated; rigid, excellent optical quality and cheap, but requiring a large incision.

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Foldable materials dominate today: hydrophobic acrylic (high refractive index so the optic is thin, excellent capsule adhesion and the lowest PCO rates, but may show glistenings), hydrophilic acrylic (hydrogel) (very biocompatible and easily folded, but prone to calcification in certain circumstances) and silicone (fast unfolding; avoided in eyes that may need silicone oil tamponade, to which it adheres). • Optical types: monofocal (one focal distance, spectacles needed for near), multifocal and extended-depth-of-focus (spectacle independence at the cost of haloes and reduced contrast), toric (corrects astigmatism, and must be aligned precisely on the correct axis), accommodating, and blue-light-filtering or UV-blocking chromophores.

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Phakic IOLs are implanted in addition to the natural lens to correct high myopia. • Power calculation is the engineering heart of the operation: biometry measures the axial length (by optical coherence or ultrasound) and the corneal curvature (keratometry), and a formula (SRK/T, Barrett, Hoffer Q and others) predicts the required dioptric power — an error here gives a clear but out-of-focus eye. • Complications:

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PCO, decentration or dislocation, incorrect power, glare and dysphotopsia, capsular contraction, uveitis-glaucoma-hyphaema syndrome, and endophthalmitis (rare but devastating).

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Corneal Implants and Keratoprostheses • Corneal transplantation (keratoplasty) with donor tissue — penetrating or lamellar (DALK, DSAEK, DMEK) — is the first-line treatment for corneal opacity and is a biological graft rather than an implant.

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The cornea's avascularity and relative immune privilege give it the highest success rate of any human transplant. • Keratoprosthesis (artificial cornea) is reserved for eyes in which repeated grafts have failed or the ocular surface is too hostile for donor tissue: the Boston KPro (a PMMA optical cylinder assembled with a titanium back plate and a donor corneal carrier) and the osteo-odonto-keratoprosthesis (a PMMA optic supported by the patient's own tooth root and alveolar bone) are the established designs.

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The central engineering problem is achieving a durable seal between a synthetic optic and living tissue; failure modes are tissue melt around the device, extrusion, retroprosthetic membrane, infection and glaucoma. • Other corneal devices: intrastromal corneal ring segments (PMMA) implanted to flatten and regularise the cone in keratoconus; corneal inlays for presbyopia; and collagen crosslinking (a treatment rather than an implant).

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Glaucoma Drainage Devices • Glaucoma (1.3) involves optic nerve damage usually associated with raised intraocular pressure caused by obstructed aqueous outflow.

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When drops and laser fail, surgery creates an alternative drainage route: trabeculectomy (a tissue procedure) or an implanted device. • Glaucoma drainage implants (tube shunts) — the Ahmed, Baerveldt and Molteno devices — consist of a silicone tube placed in the anterior chamber conducting aqueous to an end plate (silicone or polypropylene) sutured to the sclera, around which a filtering bleb forms.

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Valved devices (Ahmed) include a pressure-sensitive membrane to limit early hypotony; non-valved devices (Baerveldt, Molteno) require a temporary ligature. • Minimally invasive glaucoma surgery (MIGS) devices are much smaller stents placed into Schlemm's canal or the suprachoroidal or subconjunctival space — the iStent (titanium), Hydrus (nitinol) and XEN gel stent (crosslinked porcine gelatin) — offering a better safety profile with more modest pressure reduction. • The limiting factor for all of them is the host response of 2.6: fibrosis of the bleb or around the plate progressively restricts outflow and is the commonest cause of late failure, which is why antifibrotic agents (mitomycin C, 5-fluorouracil) are used and why surface modification to resist fibrosis is an active research area.

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Other complications are hypotony, corneal endothelial cell loss from tube contact, tube erosion and diplopia.

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Orbital, Scleral and Retinal Implants • Orbital implants replace the volume of an eye removed by enucleation or eviscerated.

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Non-integrated implants are smooth PMMA or silicone spheres; integrated (porous) implants of porous hydroxyapatite, porous polyethylene or porous alumina become vascularised, resist migration and extrusion, and can be coupled to the prosthetic shell by a peg to transmit motility.

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The visible ocular prosthesis itself is a custom-painted PMMA shell. • Scleral buckles for retinal detachment are silicone bands, sponges or tyres sutured to the sclera to indent the eye wall and relieve vitreoretinal traction; intraocular tamponade uses gases (SF₆, C₃F₈) or silicone oil. • Retinal prostheses (the 'bionic eye') aim to restore some vision in outer retinal degeneration — retinitis pigmentosa and age-related macular degeneration — where the photoreceptors are lost but the inner retina and optic nerve survive.

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A camera or photodiode array converts the image into patterns of electrical stimulation delivered by a microelectrode array placed epiretinally (on the inner surface), subretinally (in the photoreceptor layer) or suprachoroidally; the Argus II and Alpha-IMS were the first to reach patients.

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Outputs are crude — phosphene-level perception allowing light localisation and some shape recognition, not useful reading vision — and the engineering challenges are severe: hermetic encapsulation in a warm saline environment, the high electrode count and stimulation charge density needed for resolution without tissue damage, power and data transmission through the eye wall, mechanical conformity to the curved retina, and the fibrotic and glial response.

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Related approaches include cortical visual prostheses, optogenetics and gene therapy.

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Materials in Ophthalmic Surgery:

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Summary Material Ophthalmic use PMMA Rigid IOLs, keratoprosthesis optics, intrastromal rings, orbital implants and ocular prostheses Hydrophobic and hydrophilic acrylic Foldable IOLs — the dominant modern IOL materials Silicone Foldable IOLs, scleral buckles, glaucoma tubes and plates, silicone oil tamponade Hydrogels (PHEMA, silicone hydrogel) Contact lenses, some IOLs, drug-delivery inserts Titanium and nitinol Keratoprosthesis back plates, MIGS stents Porous HA, porous polyethylene Integrated orbital implants Collagen, amniotic membrane, hyaluronic acid (viscoelastic) Ocular surface reconstruction; ophthalmic viscosurgical devices that maintain the anterior chamber and protect the endothelium during surgery Platinum, iridium oxide, silicone and parylene Retinal prosthesis electrodes and encapsulation

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This section introduces tissue engineering and regenerative medicine, the tissue engineering triad, the basic procedure step by step, scaffold design and fabrication, bioreactors, and the applications and limitations of the field.

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Introduction • Tissue engineering is the application of the principles and methods of engineering and life sciences to the development of biological substitutes that restore, maintain or improve tissue function (Langer and Vacanti, 1993).

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Regenerative medicine is the broader field that also includes cell therapy, gene therapy and the stimulation of the body's own repair. • Why it is needed: transplantation is limited by donor shortage, the need for lifelong immunosuppression and disease transmission; and permanent implants (the rest of this chapter) do not grow, remodel, self-repair or fight infection, and eventually fail.

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A tissue-engineered construct should integrate, remodel and grow with the patient. • The tissue engineering triad — cells + scaffold + signals — in an appropriate mechanical and chemical environment is the organising idea of the whole field, and is the single most examinable statement in this section. • Strategies: implantation of cells alone (injected or as sheets); implantation of an acellular scaffold that recruits the body's own cells (guided tissue regeneration); implantation of a cell-seeded scaffold cultured in vitro first; and in situ tissue engineering using growth factors and matrices to stimulate host repair.

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The Three Components Component Options and requirements Cells Autologous (from the patient — no rejection, but limited numbers, requires a biopsy and time to expand, and may be diseased), allogeneic (donor — available off the shelf, but immunogenic), xenogeneic (animal — abundant, but strongly immunogenic with zoonosis risk).

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By type: differentiated (primary) cells; adult/mesenchymal stem cells from bone marrow, fat or cord (multipotent, safe, and immunomodulatory); embryonic stem cells (pluripotent but ethically contentious and tumorigenic); and induced pluripotent stem cells (iPSCs), reprogrammed from the patient's own somatic cells, which combine pluripotency with autologous origin Scaffold A temporary three-dimensional template that provides mechanical support and the architecture and surface chemistry that direct cell attachment, proliferation and differentiation, and then degrades as the cells lay down their own matrix Signals Biochemical — growth factors (BMP-2 for bone, VEGF for vessels, TGF-β for cartilage, EGF, FGF, PDGF), cytokines, adhesion peptides such as RGD; and physical — mechanical loading, fluid shear, electrical stimulation, oxygen tension and substrate stiffness and topography, which act through the mechanotransduction pathways of 2.6 Scaffold Requirements and Fabrication • Requirements of an ideal scaffold: biocompatible and non-immunogenic; biodegradable at a rate matched to tissue formation, with non-toxic degradation products; highly porous with interconnected pores — typically greater than 90 % porosity and pore sizes of about 100-400 μm for bone (large enough for cell migration and vascular ingrowth, small enough to retain surface area); mechanical properties matched to the target tissue and sufficient to withstand handling and implantation; a surface chemistry that supports cell adhesion; and it must be sterilisable, reproducible and manufacturable at scale. • Materials: natural — collagen, gelatin, fibrin, silk, alginate, chitosan, hyaluronic acid and decellularised extracellular matrix (excellent bioactivity, weaker and more variable); synthetic — PLA, PGA, PLGA, PCL, polyurethanes and PEG hydrogels (reproducible and tunable, but lacking biological recognition and releasing acidic products); ceramic — hydroxyapatite, TCP and bioglass for bone; and composites combining them. • Fabrication methods: solvent casting and particulate leaching (simple, pore size set by the porogen, but residual solvent and poor interconnection), gas foaming, freeze-drying (lyophilisation) (pore size controlled by freezing rate), phase separation, fibre bonding, electrospinning (nanofibres that mimic the dimensions of natural extracellular matrix, giving a very high surface-to-volume ratio), self-assembly of peptides, and additive manufacturing (3-D printing, fused deposition, stereolithography and selective laser sintering), which gives precise, reproducible, patient-specific architecture.

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Bioprinting deposits cells within a hydrogel bioink layer by layer, and decellularisation of a donor organ leaves its native matrix and vascular tree for recellularisation.

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The Basic Procedure of Tissue Engineering Step What is done 1.

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Cell harvest (biopsy) A small tissue biopsy or bone marrow or fat aspirate is taken from the patient (or a donor) under sterile conditions 2.

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Cell isolation The cells are released from the tissue by enzymatic digestion (collagenase, trypsin) and mechanical disaggregation, then separated and characterised 3.

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Cell expansion in culture Cells are grown in a monolayer in culture medium with serum and growth factors at 37 °C in 5 % CO₂, passaged until sufficient numbers are obtained; stem cells may be differentiated down the required lineage 4.

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Scaffold preparation The scaffold is fabricated (or a decellularised matrix prepared), shaped to the defect — increasingly from the patient's own CT or MRI data — sterilised and pre-wetted or surface-modified 5.

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Cell seeding Cells are introduced into the scaffold, statically (simple but giving poor, uneven penetration) or dynamically under perfusion, spinner flask or centrifugation (more uniform and efficient) 6.

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In vitro culture in a bioreactor The construct is matured under controlled conditions with perfusion for nutrient and oxygen transport and waste removal, and with mechanical or other physical conditioning appropriate to the tissue 7.

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Characterisation and quality control Cell viability and distribution, matrix production, mechanical properties, sterility and absence of endotoxin are assessed before release 8.

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Implantation The construct is implanted into the defect, with attention to vascular supply and fixation 9.

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Remodelling and follow-up In vivo the scaffold degrades while the cells remodel the construct into functional tissue; the patient is followed for integration, function and safety Bioreactors • A bioreactor is a device that maintains and controls the physiological environment of a construct in vitro.

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Its functions are uniform cell seeding, mass transfer of oxygen and nutrients with waste removal, control of temperature, pH, oxygen and CO₂, application of physical stimuli, and aseptic, automated, reproducible operation at a scale suitable for manufacture. • Types: spinner flask (convection at the surface), rotating wall vessel (low shear, near-free-fall suspension), perfusion bioreactor (medium forced through the scaffold — the only effective way to feed the interior of a thick construct), and tissue-specific designs that apply cyclic strain (tendon, ligament, muscle), hydrostatic or dynamic compression (cartilage, bone), pulsatile flow and shear (vascular grafts and heart valves), or electrical stimulation (cardiac and neural tissue).

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Applications and Limitations • Clinically established or close to it: cultured skin substitutes (3.4), autologous chondrocyte implantation for cartilage defects, bone graft substitutes with BMP, tissue-engineered cornea and limbal stem cell grafts, bladder and urethral constructs, and tissue-engineered trachea and vessels in small numbers of patients.

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Non-clinical applications are equally important: organ-on-a-chip and 3-D tissue models for drug testing and toxicology, and disease modelling from patient-derived iPSCs, which reduce reliance on animal testing. • The central unsolved problem is vascularisation: cells can survive only about 100-200 μm from a capillary by diffusion, so any construct thicker than a few hundred micrometres develops a necrotic core unless a vascular network is engineered into it or rapidly ingrows.

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Strategies include VEGF delivery, co-culture with endothelial cells, channelled and printed vascular architectures, and prevascularisation in vivo before transfer.

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This is why flat or thin tissues — skin, cartilage, cornea, bladder — have succeeded first and why solid organs such as liver, kidney and heart remain distant. • Other limitations: obtaining sufficient cells of the right phenotype without dedifferentiation; achieving physiological mechanical properties; immune response to allogeneic cells and to degradation products; the tumorigenic potential of pluripotent stem cells; cost, scale-up, storage and logistics; regulatory complexity, since these are combination products of cells, materials and biological agents; and ethical questions over embryonic stem cells, animal sources and chimeras.