Regenerative Medicine for Musculoskeletal and Nervous Tissues

Practice flashcards covering the principles of regenerative medicine, biomaterials, and tissue-specific engineering for bone, cartilage, muscle, and nerves.

What is the definition of regenerative medicine?

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

What does tissue engineering involve in the context of regenerative medicine?

Growing tissues, organs, or models of them in the laboratory for study or implantation.

Why is there a need for regenerative medicine regarding organ transplantation?

To address the shortage of organ donations and the issues related to organ transplantation rejection.

What are Chimeric antigen receptor T (CAR T) cells?

T cells genetically engineered to express cell surface receptors that combine antigen-binding and T cell activating functions to recognize specific antigens.

What is the difference between autologous and allogeneic cells?

Autologous cells are harvested from the patient, while allogeneic cells are obtained from a donor.

What is a major limitation of cell therapy related to the environment of implantation?

Cells are often implanted into inflammatory or dysfunctional environments, resulting in a very low survival rate of $<1\%$.

What is the function of biomaterials in regenerative medicine?

They are designed to mimic the natural extracellular matrix of target tissue or create an environment that triggers cells to rapidly regenerate tissue.

What is a hydrogel?

An insoluble hydrophilic polymer network that can be engineered with specific mechanical and biochemical properties.

What is the typical composition of a hydrogel regarding water content?

They are highly hydrated and can be composed of $>99\%$ water.

What distinguishes a 'chemical' hydrogel from a 'physical' hydrogel?

Chemical gels are covalently cross-linked, while physical gels are associative networks formed by hydrogen/ionic bonds or polymer chain entanglement.

Give four examples of natural polymers used in hydrogels.

Collagens, hyaluronic acid, alginate, and chitosan.

Which methods are used to produce porous scaffolds?

Freeze-drying (lyophilisation) and porogen leaching.

Which methods are used to produce fibrous scaffolds?

3D Printing, electrospinning, and melt electrowriting.

What are the primary problems that necessitate regenerative medicine for bone?

Large non-union fractures, cancerous lesions, degenerative diseases like osteoporosis, and infection.

What is considered the gold standard for bone grafts?

Autografts.

What are the approximate usage percentages for autografts and allografts in bone repair?

Autografts account for $60\%$ and allografts account for $30\%$.

What are three key growth factors used as biochemical stimuli for bone regeneration?

Bone morphogenetic proteins (e.g., $BMP2$), Transforming growth factor-$\beta$ ($TGF-\beta$), and Vascular endothelial growth factor ($VEGF$).

What is the 'INFUSE' example in bone regeneration, and what was its drawback?

A collagen sponge soaked in high concentrations of $BMP-2$; it led to off-target effects like ectopic bone formation and cancer.

How can micro/nanocarriers be used for controlled release in bone regeneration?

They can be loaded with drugs or growth factors (like $BMP-2$) and incorporated into alginate bioinks for 3D printing.

What polymer is often used to synthesize leaf-like microcarriers for controlled release?

Polycaprolactone (PCL).

Why does cartilage have a poor capacity to heal?

Due to a lack of innervation, avascularity, low cellularity, and a complex, dense extracellular matrix.

What is the specialized single cell type found in cartilage?

Chondrocytes.

What are the main components of the cartilage extracellular matrix?

A type II collagen mesh and large amounts of proteoglycans and glycosaminoglycans (e.g., aggrecan, chondroitin sulfate, and hyaluronic acid).

What is the typical time frame for the bioresorbability of cartilage biomaterials?

Months.

How does biomaterial stiffness affect cell phenotype in cartilage engineering?

Softer or intermediate stiffness promotes cartilage phenotypes, while stiffer materials promote bone-like cells.

Approximately what percentage of body mass is accounted for by skeletal muscle?

$40\%$.

At what point is skeletal muscle regeneration typically impaired?

When there is a loss of $20\%$ or more of the tissue.

What are the main collagen types found in the skeletal muscle extracellular matrix?

Type I and Type III.

What are the three phases involved in muscle engineering?

Pre-processing, manufacturing, and maturation phases.

What is the approximate composition of the cell population in skeletal muscle?

Muscle cells ($90\%$), fibroblasts, and adipocytes ($10\%$).

What is the maturation process for myofibers?

They are formed from fused elongated multinucleated myotubes influenced by chemical, mechanical, and electrical cues.

Why is 3D culture critical for skeletal muscle engineering?

It is essential for recreating accurate cell/myofibre structures and allowing for spontaneous or stimuli-responsive contraction.

How is a functional engineered neuro-muscular junction (NMJ) created in the lab?

By co-culturing myoblasts and pluripotent stem cell-derived neurons.

What happens when Botox is applied to an engineered neuro-muscular junction?

It blocks signalling and results in no muscle contraction.

How many cases of peripheral nerve injuries occur in Europe annually?

More than $300,000$ cases.

What are the current surgical methods for nerve repair?

Manipulative (surgically attaching ends) and bridging (inserting a supportive structure).

What is the success rate and length limit for nerve autografts?

The success rate is only $50\%$ and they are limited to a maximum length of $5\,cm$.

What is a major risk associated with nerve allografts?

Extensive immune suppression for up to $18\text{ months}$, which increases the risk of infection and tumor formation.

What are Nerve guidance conduits (NGCs)?

Supportive tubes inserted to bridge an injured nerve area and allow natural nerve regeneration to occur.

What is the required stiffness for complex nervous system biomaterial design?

$16\,Mpa$.

Name three neurotrophins used as biochemical stimuli in nerve engineering.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and Glial cell line derived neurotrophic factor (GDNF).

What two fabrication methods were combined to create complex hierarchical architecture for peripheral nerve repair?

Electrospinning and melt electrowriting.

What is the Sciatic Function Index (SFI)?

A score used to evaluate the functional recovery of the sciatic nerve, specifically measured by toe spread in rat studies.

How did the hierarchical biomaterial NGC compare to autografts in rat studies after 8 weeks?

The SFI score was not statistically different from the autograft, which is the current gold standard.

What is the role of fibroblasts in muscle injury when regeneration is impaired?

They can proliferate disproportionally, resulting in non-functional scar tissue.

What are the two common sources for mesenchymal stem cells in bone regeneration?

Bone marrow derived and adipose derived.

What is the function of the scaffold in bone repair?

It serves as an instructive framework to support rapid cell migration into the defect site.

What is the 'tidemark' in the context of musculoskeletal tissues?

The boundary between cartilage (specifically deep zone) and calcified cartilage.

What are the strategies for delivering nucleic acids in gene therapy for tissue repair?

Delivery using viral carriers or non-viral carriers (e.g., lipid or peptide encapsulation) to control the expression of proteins.

Which industry besides human medicine is interested in skeletal muscle engineering?

The lab-grown meat industry.