BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 6: Biodegradable Polymers for Tissue Engineering Last time: enzymatic degradation of solid polymers Engineering biological recognition of polymers Today: Designing polymers for tissue engineering Reading: ‘Tissue engineering- current challenges and expanding opportunities,’ L.G. Griffith and G. Naughton, Science 295, 1009 (2002) Overview of Biomaterials in Tissue Engineering Let’s review the main approaches and applications in Tissue Engienering before getting into the details of materials for TE We will review the fundamental approaches that have been taken here and return to this topic later when we discuss integration of biological molecules in synthetic biomaterials ? TE scaffolds seek to provide a surrogate for natural ECM o Provide functions of native ECM o Create a space for new tissue development o Deliver cells to site o Direct macroscopic size/shape of new tissue Tissue Engineering Approaches ? 3 major approaches o In vitro tissue genesis → in vivo application o In vivo tissue genesis → in vivo application Schematic comparison of in vitro and in vivo tissue engineering approaches 1 : Skin: bone: Lecture 6 – Biodegradable Polymers in Tissue Engineering 1 of 5 BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 o In vitro tissue genesis → ex vivo application 2 o In vitro tissue genesis → in vitro application e.g. tissue on a chip approaches 3 : Macroscopic TE Scaffold Structure ? Early attempts at designing scaffold for tissue engineering simply used forms of processed polymers: o PGA mesh fibers ? From here, the need for a higher surface area and more ‘enclosed’ structure were recognized and polymer foams were developed: o Freeze-dried scaffolds o particulate-leached scaffolds (Mikos 1994, Lu 2000) o Supercritical CO 2 -based scaffolds (Hile et al 2000, J Contrl Rel 66, 177) o Effervescent salt leaching (Yoon et al 2001, JBMR 42, 396) Lecture 6 – Biodegradable Polymers in Tissue Engineering 2 of 5 BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 ? More elegant approaches are now being considered: o Poly(methyl methacrylate) microspheres Colloidal crystal templating Hydrogel precursor polymerize Dissolve microspheres Ordered porous structure Optical micrograph/20 μm pores Fluorescence micrograph/60 μm pores 60 μm o Nanofiber-based structures (P. Ma) o ? Researchers have also investigated natural materials as scaffolds for tissue engineering- using processed ECM for tissue engineering (we won’t pursue here, covered in Biomaterials-Tissue Interactions) o Example materials null Decellularized tissues (Badylak 1998, Hilbert 1989) null Collagen-based gels (Ellis et al 1996) o Advantages: null Native cues present null Can preserve natural tissue microstructure o Disadvantages: null Poor mechanical properties in some cases null Difficult to process null Poor reproducibility null High cost Cellular Interactions with Synthetic Degradable Solids Used as Scaffolds? Review older literature looking directly at cells on PLGA, PLA, etc. Molecularly-Designed Surfaces for TE Reconstruction at Scaffold Surfaces Lecture 6 – Biodegradable Polymers in Tissue Engineering 3 of 5 BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Controlled Release in Tissue Engineering Cytokine delivery from scaffolds Case Study: Induction of vascularization in TE scaffolds ? Structure of vasculature ? Dual growth factor delivery from degradable scaffolds for de novo blood vessel synthesis 4 : controlled release scaffolds induce formation of more blood vessels with larger diameters: Lecture 6 – Biodegradable Polymers in Tissue Engineering 4 of 5 BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 DNA delivery from scaffolds Objective – in situ gene therapy Microenvironments for Stem Cells Application Focus: Engineering Vasculature References 1. Yannas, I. V. Tissue and Organ Regeneration in Adults (Springer, New York, 2001). 2. Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920-6 (1993). 3. Griffith, L. G. & Naughton, G. Tissue engineering--current challenges and expanding opportunities. Science 295, 1009-14 (2002). 4. Richardson, T. P., Peters, M. C., Ennett, A. B. & Mooney, D. J. Polymeric system for dual growth factor delivery. Nat Biotechnol 19, 1029-34 (2001). Lecture 6 – Biodegradable Polymers in Tissue Engineering 5 of 5