Biomaterials and Tissue Engineering: Material Classes, Implant Characteristics, Characterisation, Scaffolds and Engineered Organs
2. Implant characteristics: biocompatibility, bioactivity and biodegradability
Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application — a property of the material in its use, not of the material alone: a polymer that is excellent as a catheter may fail as a vascular graft. The host response begins within seconds as proteins adsorb onto the surface (and are exchanged over time, the Vroman effect), then proceeds through acute and chronic inflammation, macrophages and foreign-body giant cells, and usually ends with the implant walled off by a fibrous capsule. Blood-contacting materials must also avoid thrombosis and haemolysis.
| Behaviour | What happens | Example |
|---|---|---|
| Bioinert | minimal interaction; a thin fibrous capsule forms | alumina, zirconia, titanium |
| Bioactive | a surface layer of bone-like apatite forms and bonds chemically to bone | hydroxyapatite, 45S5 bioactive glass |
| Bioresorbable | the material dissolves or degrades and is gradually replaced by tissue | tricalcium phosphate, PLA, PGA |
| Toxic | surrounding tissue dies | materials that release cytotoxic ions or monomers |
Biodegradability. Polyesters such as PLA, PGA and their copolymer PLGA degrade by hydrolysis of ester bonds to lactic and glycolic acid, which the body metabolises. PGA is more hydrophilic than PLA and loses strength in weeks, PLA in months to years, PCL more slowly still; copolymer ratio tunes the rate. In bulk erosion water penetrates faster than bonds break, so the whole device loses molecular weight at once and mass late and suddenly (typical of PLA and PGA); in surface erosion bonds break faster than water penetrates, so the device thins from outside like a bar of soap (typical of polyanhydrides), which suits steady drug release. Acidic degradation products can accumulate inside a bulk-eroding device and accelerate it. Metals instead corrode, electrochemically, and their wear particles provoke inflammation and bone loss (osteolysis) around joint replacements.
3. Characterisation: AFM, electron microscopy and FTIR
Atomic force microscopy (AFM) scans a sharp tip on a flexible cantilever across the surface; a laser reflected from the back of the cantilever onto a position-sensitive photodiode measures its deflection, and a feedback loop drives a piezoelectric scanner to keep the interaction constant, tracing the topography with nanometre resolution. The force follows Hooke’s law, F = kx, with k the cantilever spring constant. Contact mode drags the tip on the surface; tapping (intermittent-contact) mode oscillates it near resonance so it touches only briefly, which avoids tearing soft biological samples; non-contact mode senses attractive forces from just above. AFM works in air or liquid on non-conducting samples, and force–distance curves (nanoindentation) give local stiffness and adhesion.
Electron microscopy uses an electron beam, whose wavelength is far shorter than light’s, so resolution reaches nanometres. The scanning electron microscope (SEM) rasters a focused beam over the surface in vacuum: secondary electrons give topographic images with large depth of field, backscattered electrons give contrast that rises with atomic number, and the characteristic X-rays excited in the sample give elemental composition by energy-dispersive spectroscopy (EDS). Non-conducting samples such as polymers and tissue are dried and sputter-coated with a thin layer of gold or carbon to prevent charging. The transmission electron microscope (TEM) passes the beam through a section thinner than about 100 nm and resolves internal structure down to the atomic scale.
Fourier-transform infrared spectroscopy (FTIR) identifies chemical bonds by the infrared frequencies at which they vibrate. A Michelson interferometer with a moving mirror produces an interferogram containing all wavelengths at once, and its Fourier transform gives the spectrum — faster and with better signal-to-noise than scanning one wavelength at a time. Spectra are plotted against wavenumber ν̃ = 1/λ, in cm⁻¹ (a wavelength of 10 µm is 1000 cm⁻¹), usually from 4000 to 400 cm⁻¹. Characteristic bands include the broad O–H stretch around 3200–3600 cm⁻¹, the C=O stretch near 1700 cm⁻¹, the protein amide I band near 1650 cm⁻¹ and amide II near 1550 cm⁻¹, and the phosphate bands of hydroxyapatite near 1000–1100 cm⁻¹. Attenuated total reflectance (ATR) probes only the top micrometres of a sample, which suits surface modification of implants.
4. Basics of tissue engineering, and scaffold fabrication
Tissue engineering combines three elements — cells, a scaffold and signals (growth factors and mechanical or electrical cues) — often matured in a bioreactor that supplies nutrients, oxygen and mechanical conditioning, to make living tissue that repairs or replaces damaged tissue. Cells may be autologous (the patient’s own, no rejection), allogeneic (another human donor) or xenogeneic (another species); stem-cell sources include embryonic stem cells, adult mesenchymal stem cells and induced pluripotent stem cells (iPSCs) reprogrammed from adult cells.
- A scaffold must be biocompatible; highly porous with interconnected pores large enough for cells to migrate and for nutrients and waste to diffuse (bone ingrowth needs pores of the order of 100 µm or more); degradable at a rate matched to new tissue formation; mechanically adequate for its site; and have a surface chemistry that cells attach to. Porosity = 1 − (apparent density/solid density).
- Conventional methods include solvent casting with particulate leaching (salt crystals dissolved out to leave pores), freeze-drying and gas foaming.
| Technique | Principle | Key parameters and outcome |
|---|---|---|
| Electrospinning | a high voltage (typically 10–30 kV) on a polymer solution draws a jet from a Taylor cone at the needle tip; the jet whips and stretches, the solvent evaporates, and fibres collect on a grounded target | voltage, flow rate, tip-to-collector distance, solution concentration and viscosity, humidity; low concentration gives beaded fibres, higher concentration thicker, uniform ones; nanometre-to-micrometre fibres mimicking the extracellular matrix; a rotating collector aligns them |
| 3D printing (additive manufacturing) | builds a scaffold layer by layer from a digital model — fused deposition of thermoplastic filament, stereolithography of photocurable resin, selective laser sintering of powder, extrusion of pastes | precise control of pore size, shape and interconnection; patient-specific shapes from CT or MRI data |
| Bioprinting | prints living cells within a bioink (hydrogels such as alginate, gelatin methacrylate, collagen) by extrusion, inkjet (droplet) or laser-assisted transfer | must work at physiological temperature and sterile conditions; nozzle shear stress lowers cell viability at high pressure; the bioink needs printability and then crosslinking to hold shape |
5. Artificial organs, organoids and organ-on-chip
An artificial organ is an engineered device that replaces or supports the function of a natural one. The haemodialyser (artificial kidney) and the membrane oxygenator of the heart–lung machine are mass-transfer devices; ventricular assist devices and total artificial hearts are pumps; cochlear implants stimulate the auditory nerve electrically; and the closed-loop artificial pancreas couples a continuous glucose sensor to an insulin pump through a control algorithm. Heart valves show the materials trade-off plainly: mechanical valves with pyrolytic-carbon leaflets last for decades but require lifelong anticoagulation, while bioprosthetic valves of glutaraldehyde-fixed porcine valve or bovine pericardium need little anticoagulation but wear out.
An organoid is a three-dimensional, self-organising cluster grown from stem cells (pluripotent or adult tissue stem cells) in a supporting gel matrix, which differentiates into several of an organ’s cell types and reproduces some of its architecture and function — intestinal, cerebral, kidney and liver organoids among them. They model development and disease and allow drug testing on a patient’s own cells, but they lack vasculature, so their size is limited by diffusion and their maturity varies.
An organ-on-chip is a microfluidic device, commonly moulded in the transparent, gas-permeable silicone PDMS, whose channels hold living cells under controlled flow — and often mechanical cues — to reproduce the functional unit of an organ. The lung-on-chip, for example, grows lung epithelium and capillary endothelium on either side of a porous membrane and stretches it cyclically to mimic breathing. Chips can be linked in sequence into multi-organ systems, and they are used to test drug effects and toxicity with human cells, reducing reliance on animal models.
Key takeaways
- Metals: strong and tough but far stiffer than bone; ceramics: hard and brittle, bioinert or bioactive; polymers: shapeable, weaker, some degradable; carbons: blood-compatible and wear-resistant; composites: tailored between their phases.
- Biocompatibility is an appropriate host response in a specific application; bioactive materials bond to bone; stress shielding comes from modulus mismatch.
- PGA degrades faster than PLA, PCL slowest; bulk erosion loses mass late, surface erosion thins steadily.
- AFM: F = kx, tapping mode for soft samples; SEM: secondary electrons for topography, backscattered for Z contrast, EDS for elements; FTIR: ν̃ = 1/λ, amide I near 1650 cm⁻¹.
- Cells + scaffold + signals; electrospinning from a Taylor cone, 3D printing layer by layer, bioprinting with cell-laden bioinks; organoids self-organise, organs-on-chip are microfluidic.
Practice questions (17)
Attempt each one before opening the answer. Every explanation names the tempting wrong option as well as the right one, because that is where marks are lost.
Which ceramic is bioactive, forming a direct chemical bond with bone?
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Answer: A — hydroxyapatite
Hydroxyapatite is chemically close to bone mineral, and a bone-like apatite layer forms on it and bonds to bone. Alumina and zirconia are bioinert — they become surrounded by a thin fibrous capsule instead of bonding, which is why they are used for wear surfaces rather than for fixation.Stress shielding around a metallic hip stem is caused mainly by
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Answer: A — the implant being much stiffer than the surrounding bone
A stem with a modulus several times that of cortical bone carries most of the load, so the bone around it is under-strained and, by Wolff’s law, resorbs — loosening the implant. Corrosion causes ion release and inflammation, and protein adsorption is the first step of the host response; neither is stress shielding.A unidirectional composite has 30% by volume of fibres with E = 200 GPa in a matrix with E = 4 GPa. Its modulus along the fibres (in GPa), by the rule of mixtures, to one decimal place, is ____.
Numerical answer — type the value.
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Answer: 62.8
Along the fibres both phases take the same strain, so E_c = V_fE_f + V_mE_m = 0.3 × 200 + 0.7 × 4 = 60 + 2.8 = 62.8 GPa. The isostress formula, which applies across the fibres, gives only 5.67 GPa.For the same composite (30% fibres of E = 200 GPa in a matrix of E = 4 GPa), the modulus perpendicular to the fibres (in GPa), by the isostress rule, to two decimal places, is ____.
Numerical answer — type the value.
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Answer: 5.67
1/E_c = V_f/E_f + V_m/E_m = 0.3/200 + 0.7/4 = 0.0015 + 0.175 = 0.1765, so E_c = 5.67 GPa — barely above the matrix, because the soft phase carries the full stress and dominates. Using the isostrain (parallel) rule gives 62.8 GPa, the value along the fibres.An FTIR absorption band lies at a wavelength of 6 µm. Its wavenumber (in cm⁻¹), rounded to the nearest whole number, is ____.
Numerical answer — type the value.
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Answer: 1667
ν̃ = 1/λ = 1/(6 × 10⁻⁴ cm) = 1666.7 cm⁻¹ ≈ 1667 cm⁻¹, in the amide I and C=O region. Using λ in metres gives 166 667 m⁻¹, which is the right value in the wrong unit.An AFM cantilever of spring constant 0.1 N/m deflects by 20 nm. The force on the tip (in nN) is ____.
Numerical answer — type the value.
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Answer: 2
F = kx = 0.1 N/m × 20 × 10⁻⁹ m = 2 × 10⁻⁹ N = 2 nN — the scale of force that makes soft cantilevers necessary for biological samples. Dividing instead of multiplying gives 5 × 10⁶, a sign that the relation has been inverted.In a scanning electron microscope, image contrast that depends mainly on the atomic number of the sample comes from
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Answer: A — backscattered electrons
Heavier nuclei scatter more of the beam elastically back out of the sample, so backscattered-electron images show compositional (Z) contrast. Secondary electrons are low-energy electrons from the top few nanometres and give topography; transmitted electrons are the TEM signal; the coating only prevents charging.Which statements about electrospinning are correct?
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Answer: A — raising polymer concentration and viscosity tends to suppress beads and increase fibre diameter; B — it uses a high voltage, typically of the order of tens of kilovolts; C — a Taylor cone forms at the needle tip before the jet is ejected
The electric field deforms the droplet into a Taylor cone and draws a jet that thins as it whips and dries; more chain entanglement at higher concentration resists the break-up into beads and yields thicker fibres. The fibres are typically tens of nanometres to a few micrometres across — the scale of the extracellular matrix — not millimetres.Comparing the degradation of poly(glycolic acid) and poly(lactic acid) under the same conditions,
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Answer: A — PGA degrades faster, being more hydrophilic
PLA carries a methyl group on each repeat unit that makes it more hydrophobic, slowing water uptake and ester hydrolysis, so PGA loses strength in weeks while PLA lasts months or more. Both do degrade, to glycolic and lactic acid, which is why their copolymer PLGA is used to tune the rate.Which statements about biodegradable polymers are correct?
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Answer: A — in bulk erosion water penetrates faster than the polymer degrades, so molecular weight falls throughout the device; B — polyanhydrides typically undergo surface erosion; C — the degradation products of PLGA are metabolised by the body
When hydrolysis is slower than water ingress the whole device degrades together (bulk erosion, typical of PLA, PGA and PLGA); very reactive anhydride bonds break at the surface before water gets in, so polyanhydrides erode from the outside. Lactic and glycolic acid enter normal metabolism. PCL is one of the slowest of the common polyesters, taking years, whereas PGA takes weeks.An organ-on-chip is best described as
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Answer: A — a microfluidic device in which living human cells under controlled flow reproduce functions of an organ
Organs-on-chips culture cells in microchannels, often PDMS, with flow and mechanical cues such as cyclic stretch, to reproduce an organ’s functional unit for drug and toxicity testing. They are not implants and not simulations; an implanted device replacing function is an artificial organ.An organoid is
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Answer: A — a three-dimensional, self-organising structure grown from stem cells that mimics features of an organ
Organoids arise when stem cells in a supporting gel differentiate and arrange themselves into several of an organ’s cell types and some of its architecture. A cell-free scaffold is only a template, a pump is an artificial organ, and a flat monolayer lacks precisely the three-dimensional organisation that defines an organoid.A polymer scaffold occupies a bulk volume of 1 cm³ and has a mass of 0.26 g; the solid polymer density is 1.3 g/cm³. Its porosity (in %) is ____.
Numerical answer — type the value.
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Answer: 80
Solid volume = 0.26/1.3 = 0.2 cm³, so porosity = 1 − 0.2/1 = 0.8 = 80%, a typical value for a tissue-engineering scaffold. Quoting 20% gives the solid fraction; dividing the density by the mass gives a meaningless 5.A bulk-eroding polymer loses number-average molecular weight by first-order kinetics with a half-life of 4 weeks. The fraction of its initial molecular weight remaining after 8 weeks (in %) is ____.
Numerical answer — type the value.
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Answer: 25
Eight weeks is two half-lives, so M_n = M_n0 × (½)² = 25% of the initial value (k = ln 2/4 per week, e−2 ln 2 = ¼). Losing half the initial value per half-life, linearly, would give 0%, which is not first-order behaviour.Which statements about bioprinting are correct?
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Answer: A — bioinks carry living cells, often in a hydrogel; B — in extrusion bioprinting, shear stress in the nozzle can reduce cell viability at high pressures; C — inkjet bioprinting deposits the bioink as droplets
A bioink is a cell-laden material, commonly alginate, gelatin methacrylate or collagen; forcing it through a narrow nozzle shears the cells, so pressure and nozzle size trade resolution against viability; inkjet heads eject discrete droplets. Cells would not survive 200 °C — that is the regime of thermoplastic fused-deposition printing, which prints cell-free scaffolds.A mechanical heart valve with pyrolytic-carbon leaflets, compared with a bioprosthetic tissue valve, typically
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Answer: A — lasts longer but requires lifelong anticoagulation
Pyrolytic carbon is extremely durable and among the most blood-compatible solids, yet the rigid valve still disturbs flow enough to make clots, so patients take anticoagulants for life. Glutaraldehyde-fixed animal tissue is the bioprosthetic valve, which needs little anticoagulation but degenerates; no heart valve is designed to dissolve.AFM tapping mode is preferred over contact mode for imaging soft biological samples mainly because it
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Answer: A — greatly reduces the lateral (shear) forces the tip applies to the sample
Oscillating the cantilever so the tip touches the surface only briefly at the bottom of each cycle avoids dragging it across the sample, which in contact mode can tear or displace soft cells and proteins. AFM uses a mechanical tip, needs no conductive coating and works in liquid — the gold coating and vacuum belong to electron microscopy.