BME 430

1. t-PA

t-PA stands for tissue plasminogen activator.
It is a protein that helps break down blood clots by changing plasminogen into plasmin.

2. Opsonization

Opsonization is the process of covering a pathogen or particle with antibodies or complement proteins so immune cells can recognize it and engulf it more easily.

3. Convection

Convection is the movement of a substance because of the bulk flow of a fluid.

4. Frustrated phagocytosis

Frustrated phagocytosis happens when an immune cell tries to engulf something that is too large to be taken in. Because it cannot swallow it, the cell releases enzymes and reactive molecules outside the cell.

5. Inflammation

Inflammation is the body’s protective response to injury, infection, or foreign material. It involves immune cells, signaling molecules, and changes in blood vessels.

6. Hypoxia

Hypoxia is a condition where a tissue does not receive enough oxygen.

7. Lyophilization

Lyophilization is freeze-drying. A material is first frozen, and then the water is removed by sublimation, meaning it changes from solid ice directly into vapor.

8. Fibrosis

Fibrosis is the excessive buildup of extracellular matrix, especially collagen, which leads to scar tissue formation.

9. Knockout model

A knockout model is an animal model in which a specific gene has been removed or inactivated so researchers can study its function.

10. Vascularization

Vascularization is the formation of blood vessels within a tissue.

Short Answer Questions

1. Describe the Langmuir model for protein adsorption and how it relates to biomaterials.

The Langmuir model explains adsorption by assuming that a surface has a limited number of binding sites, and each site can hold only one molecule. It also assumes that a single layer of molecules forms on the surface and that the adsorbed molecules do not strongly interact with each other. As the protein concentration in the surrounding fluid increases, more proteins bind to the surface until all available sites are filled and the surface becomes saturated. In biomaterials, this model is important because proteins from blood or body fluids adsorb onto the material surface very quickly, and those proteins influence cell attachment, immune reactions, and overall biocompatibility.

2. Describe the multiple roles of macrophages in wound healing. Include macrophage polarization, timing, and examples of function.

Macrophages play different roles during different stages of wound healing. Early in wound healing, M1 macrophages are more common. They are involved in the inflammatory phase and help kill pathogens, remove dead cells, and release pro-inflammatory cytokines such as TNF-α and IL-1. Later in healing, macrophages shift more toward the M2 phenotype. M2 macrophages help reduce inflammation and support repair by releasing growth factors and anti-inflammatory signals such as IL-10, TGF-β, and VEGF. They help with angiogenesis, fibroblast activity, matrix deposition, and tissue remodeling. A proper change from M1 to M2 is important. If M1 stays active too long, it can cause chronic inflammation. If M2 activity is too strong, it can increase fibrosis.

3. Explain the differences between vasculogenesis, angiogenesis, and arteriogenesis.

Vasculogenesis is the formation of new blood vessels from endothelial precursor cells or angioblasts. It is the process of building vessels from the beginning.
Angiogenesis is the formation of new blood vessels from vessels that already exist, usually by sprouting of endothelial cells.
Arteriogenesis is the enlargement and remodeling of existing small vessels into larger functional arteries, usually because of increased blood flow and shear stress.
These processes all support blood vessel formation, but they do it in different ways. Vasculogenesis creates vessels from precursor cells, angiogenesis expands the capillary network, and arteriogenesis strengthens circulation by forming larger vessels.

4. Explain what is meant by “floxing” a gene and how this is used to generate knockin and knockout animal models.

Floxing a gene means placing loxP sites on both sides of a DNA sequence. These loxP sites are recognized by the enzyme Cre recombinase. When Cre is present, it cuts or recombines the DNA at the loxP sites. This allows researchers to remove a gene, activate a gene, or change gene expression in specific tissues or at specific times. In a conditional knockout, an important part of a gene is floxed and then removed when Cre is expressed. In knockin systems, the same method can be used to activate or insert a gene in a controlled way, such as by removing a stop sequence.

5. Describe two tissue fabrication strategies for tendon interfaces and explain which one you would recommend.

One useful method is electrospinning. Electrospinning creates aligned fibers that look similar to tendon tissue. These aligned fibers can guide cell orientation and help cells make organized extracellular matrix.
Another method is 3D bioprinting or a multiphasic scaffold approach. This method can create different regions with different materials, stiffness, cells, and growth factors. This is useful for the enthesis, because the enthesis is not one simple tissue. It has a transition from tendon to fibrocartilage to bone.
I would recommend a multiphasic or graded 3D bioprinted scaffold, because it can better copy the natural transition between tendon and bone. Electrospinning is very good for making aligned fibrous tissue, but by itself it does not represent the full complexity of the enthesis as well as a graded design.

6. State and explain two assumptions behind Fick’s first law of diffusion.

Fick’s first law says that diffusive flux depends on the concentration gradient:

J=−DdCdxJ = -D \frac{dC}{dx}J=−DdxdC​

Two important assumptions are:

1. Steady-state diffusion — the concentration profile does not change with time.

2. Transport happens only by diffusion — there is no bulk fluid flow or convection.

Other common assumptions are constant diffusivity and one-dimensional transport.

7. What are the differences between the alternative and classical pathways for complement activation?

The classical pathway starts when antibodies, usually IgG or IgM, bind to an antigen and then activate C1. This means the classical pathway is antibody-dependent.
The alternative pathway does not need antibodies. It can begin when complement proteins interact directly with a foreign surface or through spontaneous activation of C3. It uses proteins such as Factor B, Factor D, and properdin.
The most important idea is that the classical pathway is linked to antibodies, while the alternative pathway is part of the innate immune response and can start directly on foreign surfaces.

8. Explain the principles behind scaffold-free tissue fabrication technologies. Give one tissue that would benefit from this approach.

Scaffold-free tissue fabrication means making tissue without using a separate synthetic scaffold. Instead, cells come together, attach to each other, and make their own extracellular matrix. This can be done using methods such as cell sheets, spheroids, or self-assembled tissue units. One advantage is that it reduces problems caused by scaffold materials, such as foreign body response or mismatch with native tissue.
A tissue that would benefit from this method is cartilage, because cartilage naturally has a lot of extracellular matrix and does not contain blood vessels. Scaffold-free methods can help maintain the chondrocyte phenotype and avoid problems from scaffold degradation.

9. Describe three design requirements for a bioreactor to grow mature brain tissue.

A bioreactor for brain tissue should have:

1. Good mass transport so oxygen and nutrients can reach the cells and waste can be removed.

2. Uniform cell distribution so the tissue develops evenly and does not have weak or empty areas.

3. A controlled environment with proper temperature, pH, oxygen levels, and low shear stress, because brain tissue is sensitive.

It may also be helpful for the bioreactor to include electrical stimulation, since neurons respond to electrical activity and this can support maturation.

10. Should organ systems in a body-on-a-chip be in parallel or in series?

In a series design, fluid goes from one organ model directly to the next. This is useful when you want to study how one organ affects another, such as the liver processing a drug before the drug reaches another tissue. The problem is that it is harder to control the environment of each organ separately.
In a parallel design, each organ model has its own branch but shares a common source. This makes it easier to control flow rate, nutrients, and conditions for each tissue.
I would recommend a parallel design for most applications, because it gives better control, better reproducibility, and more flexibility. A series system is more physiologically connected, but a parallel system is usually easier to manage and optimize.

1. Out of the following, which cell type is the most dominant during “frustrated phagocytosis”?

Correct answer: d. Macrophages

Why this is correct:

Frustrated phagocytosis happens when a macrophage tries to engulf something too large to take in. Since it cannot fully engulf it, it releases enzymes and reactive molecules outside the cell.

Why the others are wrong:

• a. Neutrophils
  Neutrophils are early inflammatory cells and can phagocytose, but they are not the main cell usually associated with frustrated phagocytosis in the foreign body response.

• b. Endothelial cells
  Endothelial cells line blood vessels. They are not phagocytic immune cells.

• c. Foreign body giant cells
  These form when macrophages fuse together later in the foreign body response, but the main cell classically linked to frustrated phagocytosis is still the macrophage.

2. Bioreactors can control all of the following parameters except:

Correct answer: a. Cognitive stimulation

Why this is correct:

Bioreactors can control physical and chemical conditions, but they do not control “cognitive stimulation.”

Why the others are wrong:

• b. pH
  Bioreactors can monitor and control pH.

• c. Mechanical stimulation
  Bioreactors can apply forces such as compression, stretch, or shear stress.

• d. Perfusion conditions
  Bioreactors can control flow rate and perfusion.

3. Which of the following provide immunity in our immune system?

Correct answer: b. B cells

Why this is correct:

B cells provide humoral immunity by making antibodies.

Why the others are wrong:

• a. Natural killer cells
  NK cells are part of innate immunity, but they do not provide antibody-based adaptive immunity like B cells.

• c. T cells
  T cells are also part of adaptive immunity, but if this question wants the best single answer for “provide immunity,” your professor marked B cells because they directly produce antibodies.

• d. T helper cells
  T helper cells support immune responses, but they do not directly produce antibodies.

4. Which component of a blood vessel is responsible for vasodilation and/or vasoconstriction?

Correct answer: d. Media

Why this is correct:

The tunica media contains smooth muscle, and smooth muscle controls blood vessel diameter.

Why the others are wrong:

• a. Adventitia
  This is the outer connective tissue layer. It mainly provides support and protection.

• b. Intima
  This is the inner lining of the vessel. It does not do most of the actual constricting or dilating.

• c. Lumina / Lumen
  The lumen is the open space inside the vessel where blood flows. It is not a wall layer.

5. Which of the following describes hypersensitivity reaction involved in cytotoxicity?

Correct answer: b. Type II

Why this is correct:

Type II hypersensitivity is cytotoxic hypersensitivity. It involves antibodies binding to cells and causing their destruction.

Why the others are wrong:

• a. Type I
  Type I is immediate hypersensitivity, like allergies and anaphylaxis.

• c. Type III
  Type III involves immune complex deposition.

• d. Type VI
  There is no standard classic “Type VI” hypersensitivity category in the usual classification.

6. From lecture, what is the maximum distance cells can be from a capillary network?

Correct answer: c. 0.2 mm

Why this is correct:

Cells usually need to be within about 100–200 micrometers of a capillary to get enough oxygen and nutrients.
0.2 mm = 200 µm.

Why the others are wrong:

• a. 0.1 mm
  This can still be a reasonable diffusion distance, but the common upper limit taught is closer to 0.2 mm.

• b. 0.5 mm
  This is too far for effective oxygen diffusion in most tissues.

• d. 1 mm
  This is much too far; cells at that distance would likely become hypoxic or die.

7. Which of the following is the critical control point of the complement system?

Correct answer: d. C3

Why this is correct:

C3 is the central point where the complement pathways come together. It is a major amplification and control step.

Why the others are wrong:

• a. C4
  C4 is involved in the classical and lectin pathways, but it is not the main central control point.

• b. C5
  C5 is important later in the cascade, especially for membrane attack complex formation, but it is downstream of the main central step.

• c. C1
  C1 starts the classical pathway only. It is not the central control point for the whole complement system.

8. Which of the following is not a component of a blood vessel?

Correct answer: c. Lumina
More properly: lumen

Why this is correct:

The lumen is the inside open space of the vessel, not a structural layer of the vessel wall.

Why the others are wrong:

• a. Adventitia
  This is a true vessel wall layer.

• b. Intima
  This is a true vessel wall layer.

• d. Media
  This is a true vessel wall layer.

Easy memory:

• Intima, media, adventitia = wall

• Lumen = empty space inside

9. Soft lithography techniques can form all of the following constructs except:

Correct answer: d. Microfluidic platforms
This is the answer your professor marked, so use it for this class.

Why this is correct for your exam:

Even though soft lithography is commonly connected with microfluidic device fabrication, your professor marked d as the exception, so that is the answer you should memorize for the assignment/exam.

Why the others are wrong:

• a. Scaffolds with precise 3D architectures
  Soft lithography can help make patterned structures with controlled features.

• b. Organ-on-a-chip
  These systems are often made using lithographic or microfabrication approaches.

• c. Scaffolds with precise topographical cues
  Soft lithography is especially useful for making surfaces with controlled patterns and topography.

Because your professor marked d, go with d in this class even if the wording feels odd.

10. The rate of adsorption to a surface does not depend on which transport mechanism?

Correct answer: c. Thermal conduction

Why this is correct:

Thermal conduction is the transfer of heat, not the transport of molecules to a surface for adsorption.

Why the others are wrong:

• a. Flow convection
  Bulk fluid flow can affect how molecules reach a surface.

• b. Diffusion
  Diffusion is one of the main ways molecules move to a surface.

• d. Thermal convection
  Convection involves fluid motion and can influence transport, unlike conduction.

• Vroman effect explains water after spicy food — False

• Wolff’s law relates to remodeling — True

• Diffusion time increases with the square of distance — True

• Sickle cell disease comes from a single nucleotide mutation — True

• Tet-Off needs tetracycline to be on — False

• Sensors and control systems are less important than stimuli delivery — False

• True biologic hypoxia begins at less than 2% oxygen — True

• HIF-1α helps regulate the hypoxia response — True

• The first thing that happens when biomaterials contact blood is protein adsorption — False

• Maximum cell concentration and diffusion distance are linearly related — False