Musculoskeletal System, Nervous System & Bioelectricity: Introduction to Regenerative Medicine

Comprehensive flashcards covering the Introduction to Regenerative Medicine lecture by Dr. Tom Hodgkinson, including the Tissue Engineering triad, biomaterials, cell types, and signaling molecules.

According to the transcript, what is regenerative medicine?

An interdisciplinary field bringing together life sciences and engineering to replace, engineer or regenerate cells, tissues or organs to restore or establish normal function.

What is the specific term for growing tissues/organs or models of them in a lab for study or implantation?

Tissue Engineering

What was the global regenerative medicine market size valued at in 2023?

USD $30.43$ billion

What is the expected compound annual growth rate (CAGR) for the regenerative medicine market from 2024 to 2030?

$$16.79\%$$

Name four factors influencing the growth of the regenerative medicine market.

1. Longevity & population increase; 2. Advancements in cell biology, genomic research and gene editing; 3. Stem cell-based therapies; 4. Post COVID reflection and industry support.

What are the three components of the Tissue Engineering Triad?

Biomaterials, Cells, and Regulatory Signals

How much of the traditional approach to replace damaged organs is represented by autografts?

$$60\%$$

What is an autograft?

An organ or tissue from self (e.g., heart bypass or skin grafting).

What are the primary disadvantages of autografts?

Limited amount of tissue and risk of infection and pain issues (donor site morbidity).

How much of the traditional approach to replace damaged organs is represented by allografts?

$$30\%$$

What is an allograft?

Donor transplantation from one human to another (e.g., kidney, heart, liver transplant).

What are the common issues associated with allografts?

Immune rejection/matching issues, lack of donors, and a potential increased risk of cancer.

How much of the traditional approach to replace damaged organs is represented by xenografts?

$$<5\%$$

What is a xenograft?

Donor organs derived from animals.

In bioengineering, what material property is often used for the ball in a total hip arthroplasty?

Titanium

What are the three main types of materials used in the Tissue Engineering Triad?

Ceramics, Synthetic Polymers, and Natural Polymers

What regulatory signals are mentioned in the Tissue Engineering Triad?

Growth Factors, Chemical Compounds, and Mechanical Stimulus

What anti-inflammatory molecule can be used to dampen a biomaterial's immune response?

$$IL-4$$

How does the mechanical stiffness of a biomaterial affect cells?

It influences cellular differentiation; for example, stiffer materials can induce stiffer tissues like bone.

Name three examples of ceramic biomaterials mentioned in the lecture.

Hydroxyapatite, Tri-Calcium Phosphate, and Bioactive Glass (Bioglass)

What do PCL and PLA stand for in the context of synthetic polymers?

$PCL$: Polycaprolactone; $PLA$: Polylactic acid

Name two polysaccharides used as natural polymer biomaterials.

Hyaluronic Acid and Chitosan

From what source is Chitosan derived?

Crustaceans

From what sources are Alginate and Agarose derived?

Alginate: Seaweed; Agarose: Algae

What is the process of Freeze drying (lyophilization) for biomaterial fabrication?

A slurry is prepared, degassed, and cooled under vacuum pressure to sublime water crystals to form a porous sponge or gel film.

How is gelation controlled during the gelatinization process?

By means of temperature, pH, light, or time.

What is Melt Electrowriting (MEW)?

A technique that combines electrospinning and 3D printing to produce fibrous scaffolds with pre-designed geometries.

What is the process of Decellularisation?

Using detergents to remove cells (containing antigens, DNA, and RNA) to leave only the protein ECM substrate.

Why are Mesenchymal Stem Cells (MSCs) popular for regenerative medicine?

They are easy to extract, display immune-privilege, proliferate extensively, and can form numerous target tissues.

What are human primary cells?

Cells isolated directly from human tissues, including blood and bone marrow, using enzymatic or mechanical methods.

What is the function of cell lines in regenerative research?

They are used as models for clinical research and drug screening, rather than being used directly in therapy.

Where are embryonic stem cells derived from?

The inner cell mass of a blastocyst.

What are induced Pluripotent Stem Cells (iPSCs)?

A type of pluripotent stem cell generated ex vivo from a somatic cell.

Which researchers first generated iPS cells?

Takahashi and Yamanaka

What four transcription factors were used to reprogram mouse fibroblasts into iPS cells?

$Oct-3/4$, $SOX2$, $c-Myc$, and $KLF4$

What are growth factors?

Proteins or molecules that stimulate cellular growth, proliferation, or differentiation by binding to receptors on cell surfaces.

Name two examples of growth factors listed in the signaling molecules section.

Insulin Growth Factor ($IGF$) and Vascular endothelial growth factor ($VEGF$)

What is the collective term for inhibitory RNAs such as mRNA, siRNA, and shRNA?

RNAi

What is the INFUSE bone graft?

A collagen sponge soak loaded with $rhBMP-2$ (recombinant human BMP-2).

What are the adverse effects associated with uncontrolled release of INFUSE bone graft growth factors?

Osteolysis, ectopic bone formation, infection, and cancer risk.

How can polymers be used to improve the delivery of rhBMP-2?

By creating microparticles that encapsulate growth factors for better controlled and safer release.

What is a Gene-Activated Scaffold (GAS)?

A scaffold that acts as an alternative to protein delivery by delivering genes (nucleic acids) to allow sustained protein release.

Name the specific vector and plasmid used in the development of SDF-1α gene-activated scaffolds.

Vector: Polyethyleneimine ($PEI$); Plasmid: $pSDF-1\alpha$

Why are non-viral vectors clinically preferred for gene delivery?

Because no integration will occur in the genome.

What non-viral carrier gave a controlled transient release of growth factors over 21 days in the provided study?

Nano $HA$ (Hydroxyapatite)

What does JNK3 stand for?

$c-Jun$ N-terminal kinase $3$

What was the purpose of identifying JNK3 as a therapeutic target?

To recapitulate children’s osteogenic capacity in adults.

What was the recorded porosity of the JNK3* scaffold?

$$> 99\%$$

According to the JNK3* study, what type of cells had their osteogenic capacity enhanced by the scaffold?

$A-MSCs$ (Adult Mesenchymal Stem Cells)

What is the focus of Tissue Engineering within the context of regenerative medicine?

Producing new cells or growing tissues/organs in the lab to replace malfunctioning or damaged cells.