Podcast
Questions and Answers
What type of graft has the highest percentage use for replacing missing or damaged organs?
What type of graft has the highest percentage use for replacing missing or damaged organs?
Which technology advancements contribute significantly to regenerative medicine?
Which technology advancements contribute significantly to regenerative medicine?
What is the purpose of the JNK3* scaffold in bone repair?
What is the purpose of the JNK3* scaffold in bone repair?
Which therapeutic molecule is NOT explicitly mentioned as targeting in regenerative medicine strategies?
Which therapeutic molecule is NOT explicitly mentioned as targeting in regenerative medicine strategies?
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Which type of therapy's continuation was supported by Novartis during the post-COVID reflection period?
Which type of therapy's continuation was supported by Novartis during the post-COVID reflection period?
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What is the main focus of regenerative medicine based strategies according to the provided information?
What is the main focus of regenerative medicine based strategies according to the provided information?
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Which type of graft is sourced from a different species?
Which type of graft is sourced from a different species?
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Which method historically received less focus in the treatment of damaged tissue?
Which method historically received less focus in the treatment of damaged tissue?
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What is one of the main clinical needs for regenerative medicine?
What is one of the main clinical needs for regenerative medicine?
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Which of the following is NOT a type of therapeutic cell population?
Which of the following is NOT a type of therapeutic cell population?
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What is one key property required for a successful biomaterial?
What is one key property required for a successful biomaterial?
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Which component plays an essential role in the tissue engineering triad?
Which component plays an essential role in the tissue engineering triad?
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What does Vascular Endothelial Growth Factor (VEGF) promote in bone tissue engineering?
What does Vascular Endothelial Growth Factor (VEGF) promote in bone tissue engineering?
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Which of the following is a concern associated with tissue grafting?
Which of the following is a concern associated with tissue grafting?
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Which term describes scaffolds that have genes integrated to promote healing?
Which term describes scaffolds that have genes integrated to promote healing?
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What was the projected growth rate of the regenerative medicine market from 2024 to 2030?
What was the projected growth rate of the regenerative medicine market from 2024 to 2030?
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Study Notes
Musculoskeletal System, Nervous System & Bioelectricity - MNB.9 Introduction to Regenerative Medicine
- The global regenerative medicine market was valued at USD 30.43 billion in 2023, and is expected to grow at a 16.79% compound annual growth rate (CAGR) from 2024 to 2030.
- Factors influencing this market growth include longevity, population increase, advancements in cell biology, genomic research, gene editing technology, stem cell-based therapies, attitudes towards embryonic stem cells, and post-COVID reflection/industry support (e.g., Novartis in CAR-T therapy).
Learning Outcomes
- ALO 1: Outline the clinical need for regenerative medicine as an alternative to conventional approaches.
- ALO 2: Discuss the various types of tissue graft and issues surrounding donor site morbidity and donor availability/matching.
- ALO 3: Describe different approaches to regenerative medicine involving materials, cells, and signaling molecules.
- ALO 4: Describe the properties required by a successful biomaterial – biocompatibility, biodegradability, architecture, immune response, mechanical properties.
- ALO 5: Describe the options available for obtaining therapeutic cell populations – allogeneic, autologous, somatic cells, stem cells, induced pluripotent stem cells, genetically engineered cells.
- ALO 6: Discuss the role of signaling molecules in regenerative medicine.
Lecture Review Questions
- Q.1: What are the different grafting methods for bone injuries/defects in humans?
- Q.2: Name and describe the components of the tissue engineering triad.
- Q.3: What tissue component does VEGF promote in bone tissue engineering?
- Q.4: What are Gene Activated Scaffolds?
- Q.5: What are the important properties of tissue engineered scaffolds, and why are they crucial in regenerative medicine?
ALO 2: Types of Grafts and Graft Substitutes
- Historically, damaged tissue was treated with mechanical closure to reduce complications.
- Autografts (60%): Use tissue from the patient themselves (e.g., heart bypass, skin grafting). Advantages include no immune rejection, but limited tissue availability. Disadvantages include potential for infection and pain.
- Allografts (30%): Use tissue from a donor (e.g., kidney, heart, liver transplants). Advantages for specific types. Disadvantages include high risk of immune rejection/matching issues and limited donor availability. Risk of cancer.
- Xenografts (<5%): Use animal tissue. Advantages include more abundant supply. Disadvantages include high risk of immune rejection and limited clinical accessibility.
ALO 3: Approaches to Regenerative Medicine
- Bioengineering strategies, like total hip arthroplasty, utilize titanium and plastic components to replace damaged joint structures.
- Regenerative medicine aims to repair using biomaterials and tissue engineering to replace artificial components with self-tissue repair.
ALO 4: Biomaterial Properties
- Biocompatibility: Cells adhere and function normally on the scaffold without triggering an immune response.
- Biodegradability: Scaffolds are designed to dissolve and allow the body to integrate new tissue.
- Architecture: Scaffold porosity (pore size and shape) influences fluid flow, nutrition delivery, waste removal and cell adhesion. Proper stiffness can support specific tissue function.
ALO 4: Types of Biomaterials
- Ceramics: Hydroxyapatite, tri-calcium phosphate, bioactive glasses.
- Synthetic Polymers: Polycaprolactone (PCL), Polylactic Acid (PLA), PHEMA, Polyethylene glycol (PEG) hydrogels, Polyacrylic acid (PAA).
- Natural Polymers: Polysaccharides, chitosan, hyaluronic acid, glycosaminoglycans.
- Composites: Combinations (e.g., collagen and hydroxyapatite).
ALO 4: Biomaterial Fabrication
- Freeze Drying (Lyophilization): Produces porous sponges or gel films by sublimating ice in a vacuum.
- Gelatinization: Crosslinking starch, gelatin, or collagens, produces hydrogels (e.g., temperature/pH-sensitive).
- Electrospinning: Creates fibers from a liquid droplet by applying an electric field.
- Decellularization: Removes cells to create a protein-based ECM scaffold.
ALO 5: Therapeutic Cell Populations
- Somatic cells: Primary cells isolated directly from various tissues (blood, bone marrow). Cell lines are cultured from a single cell for research/drug screening (not used directly in therapy).
-
Stem cells:
- Embryonic: Pluripotent cells from the inner cell mass of embryos.
- Adult: Undifferentiated cells found in various tissues, but decrease with age.
- Induced Pluripotent Stem Cells (iPSCs): Formed from somatic cells.
- Genetically Engineered Cells: Edited cells (e.g., CAR-T) to modify characteristics.
ALO 6: Signaling Molecules
- Signaling molecules (e.g., growth factors like IGF, VEGF, vitamins, ascorbic acid) stimulate cellular proliferation/differentiation.
- Scaffolds can contain growth factors.
- Bone morphogenetic proteins (BMPs) are crucial in bone formation.
- Vascular endothelial growth factor (VEGF) is involved in angiogenesis.
Commercially Used Bone Grafts
- Various approaches and associated complications.
- Challenges with uncontrolled release of BMP-2.
Controlled Release of rhBMP-2
- Microparticles encapsulating growth factors (e.g., rhBMP-2) for sustained delivery, safer and controlled release.
- Polymers (e.g., alginate, PLGA) enhance the controlled release of growth factors.
Gene-Activated Scaffolds (GAS)
- Delivering genes for sustained protein release (e.g., using pDNA, siRNA).
- Vectors (viral or non-viral) facilitate cellular uptake.
- Clinical preference for non-viral methods to avoid genome integration.
- Examples/types of scaffolds/molecules are provided.
Children Bone Healing
- Children's bone repair is faster than adults'.
- JNK3 plays a crucial role in osteogenic capacity.
- JNK3 scaffolds enhance osteogenic capacity in adult mesenchymal stem cells.
Development of JNK3 Scaffold for Bone Repair
- Scaffold design with high porosity (>99%).
- Enhanced osteogenic capacity by activating JNK3.
- Potential for improved bone repair in adults.
Take-Home Message (Regenerative Medicine)
- Regenerative medicine enhances tissue regeneration in situ by using biomaterials to release therapeutic molecules that enhance stem cells.
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