(Bone) Tissue Engineering

Dr. Zeeshan Sheikh. DipDh, DDS, MSc, M.Perio, PhD, FRCDC

Clinical Scientist in Periodontics - Assistant Professor-Tenure Track
Applied Oral Sciences & Dental Clinical Sciences. Faculty of Dentistry
Faculty of Medicine-School of Biomedical Engineering (Cross-appointment)
Scientific Affiliate-Nova Scotia Health

April 10th, 2023

1
 Defining Tissue Engineering
… an interdisciplinary field which applies the principles of engineering
and life sciences toward the development of biological substitutes that
restore, maintain, or improve tissue function” (Langer and Vacanti,
1993)

… a biomedical engineering discipline that integrates biology with

engineering to create tissues or cellular products outside the body or
to make use of gained knowledge to better manage the repair of
tissues within the body

An important aspect of TE is that we take cues from nature in

defining an engineering approach that will achieve these aims.
Tissue Engineering
 Two Potential Strategies for Bone

⚫Cell-seeded scaffolds cultured ex vivo prior to

transplantation
⚫ Mesenchymal stem cell expansion
⚫ ECM production under controlled
conditions
⚫ Potential for increased osteogenic activity and faster
integration with native tissue?
⚫Acellular scaffolds implanted immediately after injury
or bone removal

Both are likely to involve “biological cues”

Acellular Scaffolds

• Emphasis on scaffold design and use of therapeutic agents /

growth factors
• Osteogenic potential not as high as cell-seeded scaffolds?
• “++”s:
• easier to sterilize
• shelf-life
• low infection
 The “Ideal” TE Scaffold
• Biocompatibility
• non-toxic degradation products; no chronic inflammatory
response
• Support / Promote cell attachment and proliferation
• Promote angiogenesis
(matrix porosity)

Osteogenic cells

“Non-osteogenic” cells
Oxygen is a limiting factor in cell survival
The “Ideal” TE Scaffold (cont.)
• Suitable degradation rates

• Sufficient strength for the application

• Provide effective delivery of signaling molecules as

required

• Sterilizable without impacting function

 Collagen-based Scaffolds
• Inherently biocompatible
• Matrix familiarity
• Cell signaling functions
• Difficult to isolate and process (esp. large-scale)
• Recombinant collagens
⚫Limited mechanical properties
 Degradable Polymer Systems

• Potential range of fabrication options

• Ability to control resorption / degradation
• Must consider biocompatibility of leaching components, degradation
products
• Adequate mechanical properties?
• Not inherently osteoconductive

IMMIXTM
Extenders
 Degradable Calcium Phosphates & Glasses
• Osteoconductive
• Osteoinductive?
• Docking sites for BMPs?
• Processing advances
• Inherent brittleness ‘Foamed’ glass-ceramic

• Phases, macrostructure key Bio-Oss

Vitoss
Macromolecule Considerations

• What are the key biological mediators?

• Source
• Matrix attachment: desired conformation /
presentation retained?
• Concentration / dose levels
• When? Sustainability needed?
• Exogenous vs endogenous levels
 Platelet-Rich Plasma (PRP)
• Extracted during surgery
• “Buffy coat” (PRP)
• Rich in PDGF, TGF-b, IGF (growth
factors) SmartPRePTM
• Gel by initiating coagulation prior to
mixing with graft
• Used with several non-autogenous
bone graft materials
 Emdogain (Straumann)

• Topical application

• Enamel matrix proteins

(amelogenins)

• Alginate vehicle

• “TS” version: Gel with PerioGlas

AugmentTM

• Bone Graft
• rhPDGF-BB solution (0.3 mg/mL) +
β-TCP granules
• Use in Canada (2009) –
Orthopaedics

• Injectable
• rhPDGF-BB solution (0.3 mg/mL) +
β-TCP/collagen matrix)
• Clinical trials
~THANK YOU~