Biomaterials and Tissue Engineering: Immune Response, Interactions, Bioreactors, Animal Models, and Biotransport

Comprehensive vocabulary flashcards covering the key concepts, mechanisms, technologies, and definitions from Lectures 12 through 20 on immune response, biomaterial interactions, bioreactors, animal models, biotransport, and vascularization.

Inflammation

The reaction of living tissues to local injury, mediated by cellular signaling pathways.

Frustrated Phagocytosis

The process where immune cells (such as neutrophils) attempt to engulf a foreign biomaterial larger than $5\,\mu m$ and, being unable to internalize it, release chemical mediators, enzymes, and reactive species extracellularly to degrade the material.

Granulation Tissue

A hallmark tissue of normal wound healing and biomaterial response, characterized by the proliferation of fibroblasts and new capillary formation (neovascularization).

Foreign Body Giant Cells (FBGCs)

Multinucleated giant cells formed by the fusion of monocytes and macrophages upon encountering a biomaterial surface; considered a key indicator of the foreign body response.

Fibrosis

The end-stage tissue response to many biomaterial implants, marked by collagenous scar formation, myofibroblast activity, and fibrous encapsulation around the device.

Opsonization

The process by which proteins (such as antibodies like IgG or complement fragments like C3b) coat the surface of a pathogen or biomaterial, enhancing recognition and ingestion by phagocytic cells.

Major Histocompatibility Complex (MHC)

Cell-surface proteins (MHC Class I and II) that display antigens to T cells, differing significantly across individuals and species and driving tissue graft/transplant rejection.

Cytokines

Low molecular weight proteins (typically $10\text{–}200$ amino acids) secreted by immune and non-immune cells that act as signaling factors to regulate cell proliferation, differentiation, inflammation, and tissue remodeling.

M1 Macrophages

Classically activated macrophages induced by LPS or IFN-$\gamma$ that are pro-inflammatory, producing ROS, NO, TNF-$\alpha$, IL-1$\beta$, and MMPs, which degrade extracellular matrix and cause tissue destruction if prolonged.

M2 Macrophages

Alternatively activated macrophages induced by IL-4 or IL-13 that are anti-inflammatory and pro-healing, producing TGF-$\beta_1$, PDGF-BB, and matrix proteins to drive tissue regeneration and repair.

Adsorption

The attachment of individual entities (such as blood proteins) onto the outer surface of an impermeable solid material.

Absorption

The uptake of a substance into the bulk volume of a permeable material.

Langmuir Model

A theoretical model describing protein adsorption based on single-layer coverage on a surface, assuming reversible monolayer adsorption, no conformational changes upon binding, and no interactions between adjacent adsorbed molecules ($r_A = k_A \cdot C_b \cdot (1 - \theta) - k_D \cdot \theta$).

Vroman Effect

A competitive protein adsorption phenomenon where high-mobility proteins of low molecular weight arrive at a biomaterial surface first, but are gradually displaced over time by lower-mobility proteins that possess a higher thermodynamic binding affinity.

Alternative Complement Pathway

The primary complement pathway activated by most biomaterial surfaces, occurring via spontaneous low-level hydrolysis of C3 ($C3(H_2O)$) which binds Factor B and Factor D to form C3 convertase ($C3b \cdot Bb$), covalently depositing C3b onto surfaces via thioester bonds.

Classical Complement Pathway

A complement cascade initiated when the C1 complex binds to the Fc region of surface-adsorbed antibodies (IgG or immune complexes), cleaving C4 and C2 to form C3 convertase ($C4b \cdot C2b$).

Membrane Attack Complex (MAC / C5b-9)

A pore-forming complex assembled when C5b sequentially recruits complement components C6, C7, C8, and multiple C9 units to insert directly into target lipid membranes, causing target cell swelling and osmotic lysis.

FDPs (Fibrin Degradation Products)

Fragments produced when plasmin breaks down cross-linked fibrin clots; in biomaterial environments, they act as pro-healing signals that stimulate angiogenesis, endothelial and smooth muscle cell migration/proliferation, and neutrophil chemotaxis.

Thrombin

A key serine protease enzyme in the coagulation cascade that cleaves soluble fibrinogen into insoluble fibrin monomers to construct the structural meshwork of a blood clot.

Factor XIII (Transglutaminase)

An enzyme activated by thrombin ($FXIIIa$) that covalently cross-links fibrin monomers to stabilize the thrombus and slow down enzymatic degradation kinetics.

Embolism

The detachment and migration of a thrombus (or thrombus fragment) through the bloodstream, leading to downstream vascular occlusion.

Type I Hypersensitivity

An IgE-mediated immediate allergic reaction where allergen binding triggers mast cell and basophil degranulation, releasing histamine and leukotrienes.

Type II Hypersensitivity

A cytotoxic reaction mediated by IgG or IgM antibodies binding to cell-surface antigens, inducing complement activation, opsonization, or natural killer (NK) cell cytotoxicity.

Type III Hypersensitivity

An immune reaction where circulating soluble antigen-antibody aggregates deposit in host tissues, activating complement and attracting polymorphonuclear neutrophils (PMNs).

Type IV Hypersensitivity

A delayed, antibody-independent, cell-mediated reaction where sensitized $Th_1$ cells release cytokines (IFN-$\gamma$, TNF-$\alpha$) to recruit and hyperactivate macrophages $24\text{ to }72$ hours post-exposure.

Extracellular Polymeric Substance (EPS)

A protective hydrated matrix secreted by bacteria during biofilm maturation on biomaterials that shields the bacterial colony from systemic antibiotics and host immune clearance.

Off-the-shelf

A biomaterial or tissue engineering product that can be utilized in a clinical setting with minimal preparation or lead time.

Scaffold-free

Tissue fabrication techniques (such as self-organization and cell sheet engineering) that rely on cell self-assembly and cell-produced extracellular matrix (ECM) without pre-fabricated artificial structural templates.

Lyophilization (Freeze-drying)

A pore-fabrication technique where a frozen polymer solution undergoes sublimation under vacuum, causing solvent ice crystals to transition directly from solid to gas phase.

Particulate Leaching

A scaffold fabrication process where soluble porogen particles (such as salt or sugar) are mixed into a polymer solution, followed by setting and solvent leaching to yield interconnected macropores.

Bioink

A cell suspension or biomaterial solution utilized in bioprinting processes to pattern living cells and/or extracellular matrix.

Bioprinting

The use of computer-aided transfer processes for patterning and assembling living and non-living materials with prescribed 2D or 3D spatial organization.

Organ-on-a-chip

A microfluidic model system designed with single or multiple cellular compartments to mimic tissue- or organ-level physiology, cell-cell interactions, fluid flow, and nutrient transfer.

Bioreactor

An apparatus or engineered device supporting a biologically active environment to facilitate artificial 3D tissue fabrication, growth, maturation, and development during controlled in vitro culture.

Wolff’s Law

The physiological principle that healthy bone adapts and conditionally remodels in response to the mechanical loads under which it is placed ('use it or lose it').

Physiologic Conditioning

The application of bio-inspired, spatially and temporally regulated dynamic stimuli in vitro to promote tissue growth, ECM deposition, structural organization, and functional maturation.

Humanized Mouse

An immunodeficient mouse model bearing human cells, short strands of human DNA, human tissues/tumors, a humanized immune system, or components of the human microbiome.

Single Nucleotide Polymorphism (SNP)

A single base substitution difference between two genomes where surrounding DNA sequence remains unchanged; categorized as synonymous (no amino acid change) or non-synonymous (amino acid sequence changed).

INDEL (Insertion/Deletion)

A genetic mutation where a single or multiple base is inserted into or deleted from a genome, often causing frameshift mutations that result in stop loss (read-through) or stop gain (truncation).

Transgenic Animal

An animal into which exogenous DNA sequences (transgenes) have been introduced and integrated into the host genome as a single chromosomal insertion event, establishing a heritable trait.

Founder

An individual animal whose genome has been successfully altered by genetic engineering and can pass the modification to its offspring.

Floxed Gene

A gene or DNA sequence segment flanked by loxP recognition sites (loxP–Gene–loxP), targeting it for site-specific deletion, inversion, or recombination by Cre recombinase.

Transverse Aortic Constriction (TAC)

A surgical animal model that constricts the aortic arch via needle ligation to induce pressure overload, cardiac hypertrophy, heart failure, and cardiovascular stress.

Tet-On System

An inducible gene expression system where a transgene is turned ON by administering tetracycline or doxycycline, allowing rtTA to bind the Tet-response element promoter ($P_{TRE}$).

Tet-Off System

An inducible gene expression system where a transgene is turned OFF by administering tetracycline or doxycycline, which binds tTA and prevents it from binding the promoter to drive expression.

Flux ($J$)

The amount or mass of a chemical or biological species passing through a cross-sectional area per unit area per unit time.

Fick's First Law

The mathematical equation describing steady-state 1D diffusion flux: $J = -D\,\frac{dC}{dx}$, where $D$ is molecular diffusivity, $C$ is concentration, and $x$ is diffusion distance.

Hypoxia

A state broadly defined as oxygen partial pressures ($PO_2$) at or below $\sim 10\%$, with true biological tissue hypoxia occurring at $PO_2 < 2\%$.

Vasculogenesis

The aggregation and de novo assembly of angioblasts or endothelial progenitor cells (EPCs) into primitive blood vessels.

Angiogenesis

The formation of new blood vessels sprouting or branching from pre-existing vasculature via the proliferation and migration of differentiated endothelial cells.

Arteriogenesis

The maturation, enlargement, and remodeling of pre-existing collateral vessels into structurally robust, muscular arterial vessels in response to elevated fluid shear stress.

Thiele Modulus ($\Phi^2$)

A dimensionless parameter representing the reaction-to-diffusion ratio, given by $\Phi^2 = \frac{[\text{Cell}] \cdot Q_{\text{oxygen}} \cdot L^2}{C_0 \cdot D_{\text{oxygen}}}$; values must be kept $< 2$ to avoid central construct necrosis.