Tissue Engineering: a new healthcare technology

Asma Yahyouche  Biomaterials Group

Department of Materials, University of OxfordParks Road, Oxford, OX1 3PH, UK

 

Biomaterials

• Biomaterials science may be the most multidisciplinary of all the sciences which encompasses aspects of medicine, biology, chemistry, engineering and materials science.

• Biomaterials are : “Non-viable materials used in a medical devices intended to interact with biological systems” [D.F. Williams, 1987]

Biomaterials: Examples• Joint replacements • Bone plates • Bone cement • Hip Joint• Artificial ligaments and tendon

s • Dental implants for tooth fixati

on • Blood vessel prostheses • Heart valves • Skin repair devices • Cochlear replacements • Contact lenses

Hip jointHeart valve

Knee joint Skin

Biomaterials at Oxford

Nano-SIMS characterization

of TeethDrug Delivery Systems

Biomaterials Group Materials Dept.

In vitro TestingCell culture

Tissue expanderTissue Engineering

• Disease (e.g cancer, infection).• Trauma (e.g accidental, surgery).• Congenital abnormalities (e.g birth

defects).

• Current clinical treatment based on:

Human Tissue Damage

Grafts and Transplants

Artificial Biomaterials

Organ transplant

• High cost : $400B in USA each yearUS: 1July 2001- 30 June 2002

[Cooper .T (1987): Human Organ Transplantation: Societal, medical-legal, regulatory, and Reimbursement Issues ed. Cowen D.H et al, Health Administration Press Ann Arbor, MI, pp. 19-26]

Organ transplant

No. patients on waiting list

No. patients received

treatment

No. Patients died waiting

Cost per operation in 1987

Lung 3 757 1 071 463 -

Heart 4 097 2 155 589 $ 110 000

Kidney 50 240 14 385 3 052 $ 30 000

Liver 17 379 5 261 1 861 $ 238 000

Pancreas 1 151 541 28 $ 40 000

Example: Bone Fractures in UK

• Bone is second transplanted tissue after blood.• Healthcare in the United Kingdom alone set to

cost over 900£ million each year.• Each year in the UK: 150,000 fractures due to

osteoporosis• Hip fracture is associated with high morbidity and

mortality.• 30-50% of these hip operations with require

subsequent revision surgery.

• 50,000 hip replacements (arthroplasties) in Britain each year.• Hydroxyapatite porous coatings in orthopaedic prostheses: Bioactivity, Osteoconductivity.• Problem: Infections in orthopedic surgery (10% of cases)

Total Hip Joint Replacement

Biomaterials

• Prostheses have significantly improved the quality of life for many ( Joint replacement, Cartilage meniscal repair, Large diameter blood vessels, dental)

• However, incompatibility due to elastic mismatch leads to biomaterials failure.

Conclusion• Tissue loss as a result of injury or disease, in

an increasing ageing population, provide reduced quality of life for many at significant socioeconomic cost.

• Thus a shift is needed from tissue replacement to tissue regeneration by stimulation the body’s natural regenerative mechanisms.

• National Science Foundation first defined tissue engineering in 1987 as “ an interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain or improve tissue function”

Tissue Engineering

Tissue engineering

• Potential advantages: – unlimited supply – no rejection issues– cost-effective

Bioreactorsystem

Scaffold

Biopsy

mechanical stimuli

electrical stimuli

chemical stimuli

Human Cell Suspension

Nutrients, Growth Factors

Implantationoperation

H

Scaffolds• A 3D substrate that is key

component of tissue engineering• It needs to fulfil a number of

requirement: - Controllably Porous structure - Interconnecting porosity - Appropriate surface chemistry - Appropriate mechanical

properties - Biodegradable material - Tailorable

Scaffolds Materials

• Synthetic polymers:

Aliphatic polyesters such as polyglycolic acid (PGA), polylactic acid ( PLLA), copolymers ( PLGA) and polycaprolactone ( PCL) are commonly used in tissue engineering.

• Natural polymers:

Most popular natural polymer used in tissue engineering is collagen.

Synthetic polymers

• More controllable from a compositional and materials processing viewpoint.

• Scaffold architecture are widely recognized as important parameters when designing a scaffold

• They may not be recognized by cells due to the absence of biological signals.

Natural polymers

• Natural materials are readily recognized by cells.

• Interactions between cells and biological ECM are catalysts to many critical functions in tissues

• These materials have poor mechanical properties.

Cells

Chen and Mooney Pharmaceutical Research, Vol. 20, No. 8, August 2003.

Cells

Growth factors

[3H] thymidine uptake of chondrocytes encapsulated in collagen/chitosan/GAG scaffolds with and without TGF-β1 microspheres (S, S-TGF).

Cumulative TGF-β1 release from

chitosan microspheres.

J.E. Lee et al. / Biomaterials 25 (2004) 4163–4173

Oxford Biomaterials group

• Collagen

• Rapid prototyping: 3D wax printer

Why collagen?

• It is the ideal scaffold material:

is an important ECM molecule and is the major structural component in the body.

posses ideal surface for cell attachment in the body. biocompatible and degrades into harmless products

that are metabolized or excreted. a very poor antigen , non-toxic.

Collagen processing

• This technique allow the control over pore size and porosity.

• Achieved through variation of freezing temperature and collagen dispersion concentrationDry collagen scaffold

Indirect Solid Freeform fabrication (ISFF)

Computer Aided Design

AutoCAD design

Scaffold

Jet Head

Mill

Elevator

21 Dissolve away biosupport

Collagen/HA

casting

Negative mould

Freezing

at -30°CRemoval of BioBuildCritical Point Drying

Negative mould fabrication process

Collagen scaffold fabrication

3-D printing

From Dr. Chaozong Liu Printing video

Tissue engineering scaffold: controlled architecture

Featured with: Pre-defined channels; with highly porous structured matrix; With suitable chemistry for tissue growth – Collagen or HA No toxic solvent involved, it offers a strong potential to integrate cells/growth factors with the scaffold fabrication process.

From Dr. Terry Socholas

Advantages of ISFF• Control of the external structure:

Technology: CT/MRI CAD

Heart valve tissue engineering

Valve cells Collagen scaffold of heart valve

Heart valve post- implantation

Scaffolds with microchannels

Design

SEM images of scaffolds with channels and open porosity.

Aclian Blue staining revealed that extensive chondrogenesis were produced along the channels. Sirius Red staining revealed collagens production ( osteogenesis) in the periphery.

hMSCs seeded channelled collagen scaffold stained with Sirius Red and Alcian Blue

Take home message

• Biomaterials are materials interact with biological tissue

• It’s a multi-disciplinary subject• Important application include

– efficient drug delivery in the body– Development of artificial tissue replacement similar to

the original for clinical use– By tracking elemental fluctuation archaeology

information can be revealed