Bioengineering Concepts Summary

Biomechanics, Prosthesis, and Rehabilitation

• Biomechanics: The study of the mechanical properties of tissues.

• Prosthesis: Artificial devices that replace missing body parts.

• Rehabilitation: The process of restoring physical, psychological, social, and economic well-being.

Bioprinting

• Bioprinting: 3D printing of biological tissues and organs.

• Involves bioinks, 3D printers, and the creation of 3D printed organs both in vitro and in vivo.

Biomaterials

• Biomaterials: Materials used in medical devices and implants.

• Types: natural, synthetic, hybrid, metal-based, polymer-based, ceramic-based. Includes inorganic glasses.

Tissue Engineering

• Tissue Engineering: The use of cells, engineering, and materials methods to improve or replace biological functions.

• Principle: Combining cells, scaffolds, and bioactive molecules.

Components of Tissue Engineering

• Cells

  • Sources: autologous, allogenic, xenogenic, syngenic

  • Types: differentiated, stem cells

  • Extraction methods: bulk extraction (centrifugation), digestion (enzymatic to remove scaffold)

• Extracellular Matrix (Scaffold)

  • Functions: cell attachment and migration, delivery of biochemical factors, diffusion of nutrients.

  • Properties: high porosity, biodegradability, non-immunogenicity, structural integrity.

  • Materials: natural (collagen, fibrin, chitosan), synthetic (PuraMatrix, PLA, PGA, PCL)

• Biological Active Molecules

  • Signaling: growth factors, hormones, morphogenetic proteins, iRNA

Examples in Tissue Engineering

• Bioartificial liver device

• Artificial pancreas

• Artificial bladders

• Lab-grown cartilage for knee repair

• Artificial skin

• Artificial bone marrow

Mechanical Properties of Tissues and Organs

• Stiffness varies across different tissues and organs.

• Examples:

  • Fluid, blood, or mucus: $10^{-1}$ kPa

  • Lung: $10^0$ kPa

  • Breast: $10^1$ kPa

  • Endothelial tissue, adipose tissue, smooth muscle tissue: around $10^1$ kPa

  • Stromal tissue, skeletal muscle tissue: around $10^2$ kPa

  • Plastic, glass, myocardium, artery, skin: around $10^2-10^3$ kPa

  • Neural tissue, cartilage: around $10^3$ kPa

  • Bone: $10^3 - 10^4$ kPa

  • BOLON: varies, but higher than $10^4$ kPa

  • Elastic modulus of bone: $2.4$ GPa

Multi-Scale Characterization Approach

• Whole body data analysis

• Organ testing (e.g., heart, liver, lung, spleen)

• Tissue testing

• Material optimization

• Techniques: tension and compression tests

Biomechanical Properties of Bone Matrix

• Effects of mechanical stimuli on bone matrix components (Col and HA) and bone-related cells (mesenchymal stem cells, osteocytes, osteoblasts, osteoclasts).

Prosthetics

• Prosthesis: An artificial device to replace a missing body part.

• Prosthetics: The field of research and expertise in designing and building artificial limbs.

• Types: transradial, transhumeral, transtibial, and transfemoral.

• Powering: body-powered, motor-powered, myoelectric

Rehabilitation

• Involves six major areas of focus:

  • Preventing and managing comorbid illness and medical complications.

  • Training for maximum independence.

  • Facilitating psychosocial coping and adaptation.

  • Preventing secondary disability through community reintegration.

  • Enhancing quality of life.

  • Preventing recurrent conditions.

Benefits of Rehabilitation

• Physical: Increases physical capacity, reduces pain, strengthens muscles, improves balance and coordination, improves flexibility and joint mobility, reduces swelling, prevents deformities, improves gait and posture.

• Psychological: Enhances self-confidence and ability to deal psychologically with illness or injury, provides greater independence and mental well-being.

• Social: Improved participation, decreased dependence, improved quality of life, quicker return to work, supports return to sport or exercise.

• Economic: Reduces costs of nursing, residential, and social care, reduces the risk and associated costs of mental health illness and diabetic care, reduces length-of-stay costs, realizes the potential of children and young people.

Bioprinting Details

Bio-ink

• Composition: Biopolymers + cells

• Properties: chemical, physical, physico-chemical

• Types: Natural, Synthetic, Hybrids

• Charge: Ionic, Cationic, Anionic, Non-ionic

• Polymer:

  • Type: Homopolymer, Copolymer, Interpolymer

  • Performance: Commodity, Smart

  • Degradation: Biological, Non-Biological

Bioprinting Techniques

• Extrusion

• Droplet

• SLA (Stereolithography)

• DLP (Digital Light Processing)

• Laser-based

Bioprinting Process

1. Imaging (X-Ray, CT scan, MRI)

2. Design Approach (Biomimicry, self-assembly, mini tissues)

3. Material Selection (Synthetic or Natural polymers, decellularized ECM)

4. Mechanical Force

5. Cell Selection (Differentiated, Pluripotent stem, Multipotent stem cells)

6. Application (Implantation, in vitro testing)

3D Printing of Organ Models

• Methods: Direct and Indirect.

• Printing techniques: Material Extrusion, Material jetting, Binder jetting, Vat photopolymerization, SLS

• Printing materials: Plastic, Metal, Resin, Plaster, Hydrogel

• Casting/Coating Materials: Silicone, Polyurethane, PVA, ABS, PDMS, HIPS, Wax

3D Printing Technologies

• A) Stereolithography (SLA)

• B) Digital light processing (DLP)

• C) Material jetting (Polyjet printing)

• D) Material extrusion (FDM printing)

• E) Power bed fusion

• F) Binder jetting

Comparison of Bioprinting Techniques

Evolution of Biomaterials

Generations of Biomaterials

• First Generation (1950s-1970s): Bioinert (Metals & Alloys)

• Second Generation (1970s-1990s): Bioactive or bioresorbable (Bioceramics & polymers)

• Third Generation (1990s-2010s): Bioactive & Biomimetic (Nano-composites)

• Fourth Generation (2010s-Present): Tissue engineered scaffolds

Historical Timeline

• 2000 BC: Linen thread for wound healing

• 200 BC: Metallic sutures with golden wire

• XVI-XIX centuries: Golden plates for cranial fracture, bamboo dental implants, iron artificial teeth

• 1939: First use of a polymer as biomaterial

• 1950: Metals for hard tissue replacement

• 1970: Bioactive/bioresorbable materials (ceramics and polymers)

• 2010: Regenerative - hydrogels, 3D bioprinting, engineered tissues/organs

Biomaterials Applications

• As Scaffold: For generation of new cells and tissues

  • Provide cells with a substrate for growth and mechanical integrity post-implantation

  • Synthetic x natural

  • Metals, Ceramics, Polymers, Composites

• As Signaling Molecule: To build communication between old and new tissue

  • Bioactive molecules induce cell proliferation, differentiation, and metabolic activity.

Cells as Building Blocks

• Living fibroblasts (skin) or chondrocytes (cartilage)

• Cell division - extension of telomerase activity (1998)

• Heyflick limit

• Extraction of cells:

  • Bulk extraction (centrifugation)

  • Digestion (enzymatic to remove the scaffold) - Collagenase: preferred reagent

Extracellular Matrix or Scaffold

Functions:

• Allow cell attachment and migration.

• Deliver and retain cells and biochemical factors.

• Enable diffusion of vital cell nutrients and expressed products.

• Exert certain mechanical and biological influences to modify the behavior of the cell phase.

Properties of Material

• High porosity and an adequate pore size.

• Biodegradability or desired resorption rate.

• Non-immunogenicity.

• Low concentration.

• Structural integrity at the nano-level.

• Injectability.

Source of Material for Scaffold

• Natural: Derivatives of the extracellular matrix – proteic material such as collagen or fibrin, polysaccharidic material: chitosan or glycosaminoglycans (GAG) with cross linking agents.

• Synthetic: PuraMatrix, PLA - polylactic acid (polyester). Polyglycolic acid (PGA) and polycaprolactone (PCL).

Methods for Synthesis of a Scaffold

1. Molecular Self-Assembly: Biomaterials with properties similar to the natural in vivo extracellular matrix (ECM).

   • Merit: superior in vivo toxicology and biocompatibility.

2. Textile technologies: Preparation of non-woven meshes of different polymers.

   • Drawback - difficulties of obtaining high porosity and regular pore size.

3. Solvent Casting & Particulate Leaching (SCPL):

   • Merit: Regular porosity

   • Drawback - organic solvents may cause damage to the cells seeded on the scaffold.

4. Gas Foaming:

   • Merit: No use of solvents

   • Drawbacks: prohibits use of temperature labile material & pores do not form an interconnected structure.

5. Emulsification/Freeze-drying:

   • Merit: does not require the use of a solid porogen like SCPL

   • Drawbacks - it still requires the use of solvents, pore size is relatively small and porosity is often irregular

6. Thermally Induced Phase Separation (TIPS):

   • Drawbacks: same drawbacks of emulsification/freeze-drying.

7. CAD/CAM Technologies:

   • First a three-dimensional structure is designed using CAD software, then the scaffold is realized by using ink-jet printing of polymer powders or through Fused Deposition Modeling of a polymer melt.

Problems Associated with Tissue Engineering

• Mass transport limitations

Basic Principles of Tissue Engineering

• Cells from a biopsy -> Monolayer cell culture -> Expanded cells -> Culture on a 3D polymeric scaffold -> Generation of a graft

• Biomechanics: Study of tissue mechanical properties.

• Prosthesis: Artificial body part replacements.

• Rehabilitation: Restoring physical, psychological, social, and economic well-being.

• Bioprinting: 3D printing of biological tissues/organs using bioinks and 3D printers.

• Biomaterials: Materials for medical devices/implants. Types: natural, synthetic, hybrid, metal, polymer, ceramic.

• Tissue Engineering: Improving/replacing biological functions using cells, engineering, and materials; combining cells, scaffolds, and bioactive molecules.

  • Cells: autologous, allogenic, xenogenic, syngenic types; differentiated, stem cells; extraction via centrifugation or enzymatic digestion.

  • Extracellular Matrix (Scaffold): Provides cell attachment, biochemical factor delivery, nutrient diffusion; high porosity, biodegradability, non-immunogenicity, structural integrity; natural (collagen, fibrin, chitosan), synthetic (PuraMatrix, PLA, PGA, PCL) materials.

  • Biological Active Molecules: Signaling via growth factors, hormones, morphogenetic proteins, iRNA.

• Examples include bioartificial liver devices, artificial pancreas/bladders, lab-grown cartilage, artificial skin/bone marrow.

• Mechanical Properties of Tissues and Organs: Stiffness varies (examples given in kPa).

• Multi-Scale Characterization Approach: Whole body, organ, tissue testing, material optimization; techniques: tension/compression tests.

• Biomechanical Properties of Bone Matrix: Effects of mechanical stimuli on bone matrix components and cells.

• Prosthetics: Designing/building artificial limbs (transradial, transhumeral, transtibial, transfemoral); powered by body, motor, or myoelectricity.

• Rehabilitation: Focus on preventing complications, training independence, psychosocial coping, preventing secondary disability, enhancing life quality, preventing recurrence.

  • Benefits: physical (increased capacity, reduced pain, improved balance), psychological (self-confidence, mental well-being), social (improved participation, quality of life), economic (reduced costs of care).

• Bioprinting Details:

  • Bio-ink: Biopolymers + cells; properties: chemical, physical; types: natural, synthetic, hybrids; polymers: homopolymer, copolymer, interpolymer, commodity, smart, biological/non-biological degradation.

  • Bioprinting Techniques: Extrusion, Droplet, SLA, DLP, Laser-based.

  • Bioprinting Process: Imaging, design, material selection, mechanical force, cell selection, application (implantation, in vitro testing).

  • 3D Printing of Organ Models: Direct/Indirect methods; material extrusion, jetting, binder jetting, vat photopolymerization, SLS; plastic, metal, resin, plaster, hydrogel materials.

  • 3D Printing Technologies: SLA, DLP, Material jetting, Material extrusion, Power bed fusion, Binder jetting.

  • Comparison of Bioprinting Techniques: Droplet, Extrusion, Laser-assisted, SLA/DLP (features compared: droplet size, print speed, cell density, cell viability, printer cost, resolution, advantages, disadvantages).

• Evolution of Biomaterials:

  • Generations: Bioinert (1st), Bioactive/resorbable (2nd), Bioactive/biomimetic (3rd), Tissue engineered scaffolds (4th).

  • Timeline: Linen thread (2000 BC), metallic sutures (200 BC), golden plates (XVI-XIX centuries), polymer use (1939), metals (1950), bioactive materials (1970), regenerative materials (2010).

  • Biomaterials Applications: Scaffold for new cells/tissues (synthetic x natural, metals, ceramics, polymers, composites), signaling molecule for cell communication.

• Cells as Building Blocks: Living fibroblasts/chondrocytes, cell division, Heyflick limit, extraction via centrifugation or enzymatic digestion (collagenase).

• Extracellular Matrix/Scaffold: Functions (cell attachment, biochemical factor delivery, nutrient diffusion, mechanical/biological influences), properties (high porosity, biodegradability, non-immunogenicity, structural integrity, injectability), source (natural: collagen, fibrin, chitosan; synthetic: PuraMatrix, PLA, PGA, PCL).

• Scaffold Synthesis Methods: Molecular self-assembly, textile technologies, Solvent Casting & Particulate Leaching (SCPL), Gas Foaming, Emulsification/Freeze-drying, Thermally Induced Phase Separation (TIPS), CAD/CAM Technologies.

• Problems: Mass transport limitations.

• Basic Principles: Cells from biopsy -> monolayer culture -> expanded cells -> culture on 3D scaffold -> graft generation.