Matrix metalloproteinase activity and inhibition in articular cartilage : effects on composition and biophysical properties and relevance to osteoarthritis

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1995.Includes bibliographical references (leaves 172-183).by Lawrence Justin Bonassar.Ph.D

Customized biomaterials to augment chondrocyte gene therapy

A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30 days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins

A Study of Variable Stiffness Alginate Printing for Medical Applications

Technologies for multi-material 3D-printing of anatomical shapes are useful both for fabrication of heterogeneous cell-seeded implants as well as for fabrication of synthetic models for surgical planning and training. For both these applications, it would be desirable to print directly with biological materials to best emulate the target’s properties. Using a novel material platform, we describe a series of experiments attempting to print variable-stiffness hydrogels. We vary compliances by alternating 2% alginate hydrogel and a Dextran-infused calcium chloride post-crosslinker. Stiffness throughout the construct ranged from 4 kPa to 20 kPa as a function of post-crosslinker concentration, which was spatially specified by the user.Mechanical Engineerin

Improved Quality of 3D-Printed Tissue Constructs Through Enhanced Mixing of Alginate Hydrogels

While alginate hydrogel is a desirable material platform for Solid Freeform Fabrication (SFF) of cell-seeded tissue engineering scaffolds, achieving consistently high-quality results can be challenging. Local variations in the material properties cause inconsistent material deposition behavior and consequently decrease the resultant geometric fidelity of the construct. The effects of gel mixing on material property consistency, geometric fidelity, and cell viability were characterized in an attempt to improve the formulation’s compatibility with SFF processing. Material homogeneity was quantified through a novel experimental setup composed of an EnduraTEC mechanical test-frame and custom syringe-extrusion jig. Cell viability and geometric fidelity were assessed using standard protocol. The baseline mechanical stiffness of the printed samples was 16±3 kPa (n=6). We found that increasing mixing reduced material inconsistency and improved geometric fidelity, without adversely affecting cell viability: the printed construct quality was drastically improved by increasing mixing well beyond previously established limits.Mechanical Engineerin

Boundary mode lubrication of articular cartilage with a biomimetic diblock copolymer

We report the design of a diblock copolymer with architecture and function inspired by the lubricating glycoprotein lubricin. This diblock copolymer, synthesized by sequential reversible addition–fragmentation chain-transfer polymerization, consists of a cationic cartilage-binding domain and a brush-lubricating domain. It reduces the coefficient of friction of articular cartilage under boundary mode conditions (0.088 ± 0.039) to a level equivalent to that provided by lubricin (0.093 ± 0.011). Additionally, both the EC50 (0.404 mg/mL) and cartilage-binding time constant (7.19 min) of the polymer are comparable to purified human and recombinant lubricin. Like lubricin, the tribological properties of this polymer are dependent on molecular architecture. When the same monomer composition was evaluated either as an AB diblock copolymer or as a random copolymer, the diblock effectively lubricated cartilage under boundary mode conditions whereas the random copolymer did not. Additionally, the individual polymer blocks did not lubricate independently, and lubrication could be competitively inhibited with an excess of binding domain. This diblock copolymer is an example of a synthetic polymer with lubrication properties equal to lubricin under boundary mode conditions, suggesting its potential utility as a therapy for joint pathologies like osteoarthritis

Biological approaches to spinal disc repair and regeneration for clinicians/ [edited by] Roger Härtl, Lawrence J. Bonassar.

Includes bibliographical references and index.Although there have been significant advancements in minimally invasive spinal surgery techniques in the last few decades, optimal outcomes for chronic low back pain remain elusive. A number of promising clinical trials have been conducted using tissue engineering and biological interventions for disc degeneration. Written by renowned innovators, this is the first book that covers implementation of these groundbreaking approaches for disc disease. The text begins with key fundamentals including anatomy and physiology, pathophysiology, imaging and biomechanics to delineate healthy versus diseas.The human spinal disc : relevant anatomy and physiology / Julien Tremblay-Gravel, Fahad H. Abduljabbar, Jean Ouellet, and Lisbet Haglund -- Pathophysiology of disc disease : disc degeneration / Niloofar Farhang, Joshua Stover, Brandon Lawrence, and Robby D. Bowles -- Imaging of the healthy and diseased spinal disc / Darryl B. Sneag and Hollis G. Potter -- Biomechanics of the healthy and diseased spine / Hans-Joachim Wilke and Fabio Galbusera -- Differences between human and animal discs : pros and cons of current animal models for pre-clinical development of biologic therapies for low back pain / Jeffrey C. Lotz -- Grading scales for disc degeneration and regeneration : clinical and experimental / Peter Grunert -- Disc regeneration : in vitro approaches and experimental results / John T. Martin, Harvey E. Smith, Lachlan J. Smith, and Robert L. Mauck -- Intervertebral disc whole organ cultures / Marianna Peroglio, Zhen Li, Lorin Michael Benneker, Mauro Alini, and Sibylle Grad -- Biological treatment approaches : basic ideas and principles / Victor Y. Leung and Kenneth M. Cheung -- Learning from successes of tissue engineered strategies in non-spine cartilaginous disorders / Stephen Sloan and Lawrence J. Bonassar -- Treatment and of degenerative disc disease and disc regeneration : proteins and genes / Daisuke Sakai and Jordy Schol -- Treatment of degenerated disc disease/disc regeneration : growth factors and platelet-rich plasma / Koichi Masuda and Kenji Kato -- Treatment of degenerated disc disease/disc regeneration : stem cells, chondrocytes or other cells, and tissue engineering / Steven Presciutti and Howard An -- Nucleus replacement and repair : autologous disc chondrocyte transplantation / Christian Hohaus, Timothy Ganey, and Hans Jörg Meisel -- Annulus fibrosus repair / Olivia M. Torre, Michelle A. Cruz, Andrew C. Hecht, and James C. Iatridis -- Summary of clinical trials with biological treatment approaches for spinal disease / Gernot Lang, Ibrahim Hussain, Micaella Zubkov, Yu Moriguchi, Brenton Pennicooke, and Roger Härtl -- Total disc transplantation : current results and future development / Jason Pui Yin Cheung, Dike Ruan, and Keith D.K. Luk -- What have we learned from mechanical total disc replacement? / Timothy T. Roberts, Colin M. Haines, and Edward C. Benzel -- Regulatory overview : obtaining regulatory approval of a biologic/cell product / Michaela H. Purcell, Penny J. White, H. Davis Adkisson -- What makes biological treatment strategies and tissue engineering for ddd interesting to industry? / Hassan Serhan, Elliott A. Gruskin, and William C. Horton -- What will the future bring? : perspectives from around the world / Tony Goldschlager, Claudius Thome, Howard An, and Luiz Vialle.1 online resource