Influence of macromer molecular weight and chemistry on poly(beta-amino ester) network properties and initial cell interactions.

A library of photocrosslinkable poly(beta-amino ester)s (PBAEs) was recently synthesized to expand the number of degradable polymers that can be screened and developed for a variety of biological applications. In this work, the influence of variations in macromer chemistry and macromer molecular weight (MMW) on network reaction behavior, overall bulk properties, and cell interactions were investigated. The MMW was controlled through alterations in the initial diacrylate to amine ratio (> or =1) during synthesis and decreased with an increase in this ratio. Lower MMWs reacted more quickly and to higher double bond conversions than higher MMWs, potentially due to the higher concentration of reactive groups. Additionally, the lower MMWs led to networks with higher compressive and tensile moduli that degraded slower than networks formed from higher MMWs because of an increase in the crosslinking density and decrease in the number of degradable units per crosslink. The adhesion and spreading of osteoblast-like cells on polymer films was found to be dependent on both the macromer chemistry and the MMW. In general, the number of cells was similar on networks formed from a range of MMWs, but the spreading was dramatically influenced by MMW (higher spreading with lower MMWs). These results illustrate further diversity in photocrosslinkable PBAE properties and that the chemistry and macromer structure must be carefully selected for the desired application.

[1]  S. Bryant,et al.  Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. , 2002, Journal of biomedical materials research.

[2]  J A Burdick,et al.  Conversion and temperature profiles during the photoinitiated polymerization of thick orthopaedic biomaterials. , 2001, Biomaterials.

[3]  Robert Langer,et al.  Photopolymerizable degradable polyanhydrides with osteocompatibility , 1999, Nature Biotechnology.

[4]  Robert Langer,et al.  Advances in Biomaterials, Drug Delivery, and Bionanotechnology , 2003 .

[5]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[6]  Robin H. Liu,et al.  Microfluidic tectonics: a comprehensive construction platform for microfluidic systems. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  David Dean,et al.  Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds , 2001, Journal of biomaterials science. Polymer edition.

[8]  Jason A Burdick,et al.  Influence of gel properties on neocartilage formation by auricular chondrocytes photoencapsulated in hyaluronic acid networks. , 2006, Journal of biomedical materials research. Part A.

[9]  Jeffrey A. Hubbell,et al.  Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(.alpha.-hydroxy acid) diacrylate macromers , 1993 .

[10]  Jason A Burdick,et al.  Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. , 2002, Biomaterials.

[11]  J. Hubbell,et al.  Prevention of Postoperative Adhesions in the Rat by In Situ Photopolymerization of Bioresorbable Hydrogel Barriers , 1994, Obstetrics and gynecology.

[12]  Kytai Truong Nguyen,et al.  Photopolymerizable hydrogels for tissue engineering applications. , 2002, Biomaterials.

[13]  Robert Langer,et al.  Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. , 2006, Journal of biomedical materials research. Part A.

[14]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[15]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[16]  J. Hubbell,et al.  Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. , 1998, Journal of biomedical materials research.

[17]  J. Elisseeff,et al.  Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. , 2000, Journal of biomedical materials research.

[18]  Robert Langer,et al.  A Combinatorial Library of Photocrosslinkable and Degradable Materials , 2006 .

[19]  C. M. Agrawal,et al.  Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. , 2001, Journal of biomedical materials research.

[20]  Kristi S. Anseth,et al.  New Directions in Photopolymerizable Biomaterials , 2002 .

[21]  K. Burg,et al.  Biomaterial developments for bone tissue engineering. , 2000, Biomaterials.

[22]  T. Gill,et al.  Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks. , 2006, Tissue engineering.

[23]  J. Fisher,et al.  Photoinitiated Polymerization of Biomaterials , 2001 .

[24]  Robert Langer,et al.  Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery. , 2003, Journal of the American Chemical Society.

[25]  J L West,et al.  Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. , 2001, Biomaterials.

[26]  M. Grinstaff,et al.  Photocrosslinkable polysaccharides for in situ hydrogel formation. , 2001, Journal of biomedical materials research.

[27]  Stephanie J Bryant,et al.  In situ forming degradable networks and their application in tissue engineering and drug delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Robert L Sah,et al.  Probing the role of multicellular organization in three-dimensional microenvironments , 2006, Nature Methods.

[29]  G A Ateshian,et al.  Experimental verification and theoretical prediction of cartilage interstitial fluid pressurization at an impermeable contact interface in confined compression. , 1998, Journal of biomechanics.

[30]  Christine E Schmidt,et al.  Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. , 2003, Biotechnology and bioengineering.

[31]  C. Bowman,et al.  The Influence of Comonomer Composition on Dimethacrylate Resin Properties for Dental Composites , 1996, Journal of dental research.

[32]  Mark D. Miller,et al.  Review of Orthopaedics , 2000 .

[33]  Jason A Burdick,et al.  Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Robert Langer,et al.  Degradable Poly(β-amino esters): Synthesis, Characterization, and Self-Assembly with Plasmid DNA , 2000 .

[35]  Robert Langer,et al.  Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. , 2005, Biomacromolecules.