Biomedical subjects

Joseph W Freeman

Publications and source records attributed to Joseph W Freeman.

8 recordsLinked to original sources

PubMed2006

Tissue engineering of the anterior cruciate ligament using a braid-twist scaffold design.

The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee. The insufficient vascularization of this tissue prevents it from healing completely after extreme tearing or rupture, creating a need for ACL grafts for reconstruction. The limitations of existing grafts have motivated the investigation of tissue-engineered ACL grafts. A successful tissue-engineered graft must possess mechanical properties similar to the ACL; to date no commercially available synthetic graft has achieved this. To accomplish this goal we have combined the techniques of polymer fiber braiding and twisting to design a novel poly L-lactic acid (PLLA) braid-twist scaffold for ACL tissue engineering. The scaffold is designed to accurately mimic the biomechanical profile and mechanical properties of the ACL. In this study, braid-twist scaffolds were constructed and compared to braided scaffolds and twisted fiber scaffolds. The addition of fiber twisting to the braided scaffold resulted in a significant increase in the ultimate tensile strength, an increase in ultimate strain, and an increase in the length of the toe region in these constructs over scaffolds that were braided. Based on the findings of this study, the braid-twist scaffold studied was found to be a promising construct for tissue engineering of the ACL.

Anterior Cruciate Ligament↗

PubMed2005

Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies.

The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee, and limitations in existing reconstruction grafts have prompted an interest in tissue engineered solutions. Previously, we reported on a tissue-engineered ACL scaffold fabricated using a novel, three-dimensional braiding technology. A critical factor in determining cellular response to such a graft is material selection. The objective of this in vitro study was to optimize the braided scaffold, focusing on material composition and the identification of an appropriate polymer. The selection criteria are based on cellular response, construct degradation, and the associated mechanical properties. Three compositions of poly-alpha-hydroxyester fibers, namely polyglycolic acid (PGA), poly-L-lactic acid (PLLA), and polylactic-co-glycolic acid 82:18 (PLAGA) were examined. The effects of polymer composition on scaffold mechanical properties and degradation were evaluated in physiologically relevant solutions. Prior to culturing with primary rabbit ACL cells, scaffolds were pre-coated with fibronectin (Fn, PGA-Fn, PLAGA-Fn, PLLA-Fn), an important protein which is upregulated during ligament healing. Cell attachment and growth were examined as a function of time and polymer composition. While PGA scaffolds measured the highest tensile strength followed by PLLA and PLAGA, its rapid degradation in vitro resulted in matrix disruption and cell death over time. PLLA-based scaffolds maintained their structural integrity and exhibited superior mechanical properties over time. The response of ACL cells was found to be dependent on polymer composition, with the highest cell number measured on PLLA-Fn scaffolds. Surface modification of polymer scaffolds with Fn improved cell attachment efficiency and effected the long-term matrix production by ACL cells on PLLA and PLAGA scaffolds. Therefore based on the overall cellular response and its temporal mechanical and degradation properties in vitro, the PLLA braided scaffold pre-coated with Fn was found to be the most suitable substrate for ACL tissue engineering.

Absorbable Implants↗

PubMed2005

Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation.

The anterior cruciate ligament (ACL) is the major intraarticular ligamentous structure of the knee, which functions as a joint stabilizer. It is the most commonly injured ligament of the knee, with over 150,000 ACL surgeries performed annually in the United States. Due to limitations associated with current grafts for ACL reconstruction, there is a significant demand for alternative graft systems. We report here the development of a biodegradable, tissue-engineered ACL graft. Several design parameters including construct architecture, porosity, degradability, and cell source were examined. This graft system is based on polymeric fibers of polylactide-co-glycolide 10:90, and it was fabricated using a novel, three-dimensional braiding technology. The resultant micro-porous scaffold exhibited optimal pore diameters (175-233 microm) for ligament tissue ingrowth, and initial mechanical properties of the construct approximate those of the native ligament.

Absorbable Implants↗

PubMed2005

Ligament tissue engineering: an evolutionary materials science approach.

The anterior cruciate ligament (ACL) is important for knee stabilization. Unfortunately, it is also the most commonly injured intra-articular ligament. Due to poor vascularization, the ACL has inferior healing capability and is usually replaced after significant damage has occurred. Currently available replacements have a host of limitations, this has prompted the search for tissue-engineered solutions for ACL repair. Presently investigated scaffolds range from twisted fiber architectures composed of silk fibers to complex three-dimensional braided structures composed of poly (L-lactic acid) fibers. The purpose of these tissue-engineered constructs is to apply approaches such as the use of porous scaffolds, use of cells, and the application of growth factors to promote ligament tissue regeneration while providing mechanical properties similar to natural ligament.

Absorbable Implants↗

PubMed2005

The effects of prestrain and collagen fibril alignment on in vitro mineralization of self-assembled collagen fibers.

Collagen fibers are under tension in most extracellular matrices both prior to and during normal loading. This tension not only provides mechanical advantages, but also appears to establish a loading basis for the stimulation of mechanochemical transduction processes. The presence of tensile loads applied to collagen fibers also results in physical alignment of the collagen fibrils along the tensile axis. This alignment may influence biological processes such as mineralization. In this study we report a comparison between elastic and viscous stress-strain curves and mineral contents of self-assembled collagen fibers that were strained to 30% of their original lengths and then mineralized, and self-assembled collagen fibers that were not strained before being mineralized. We concluded that the application of strain changes the organization of the collagenous matrix and alters the calcium phosphate nucleation and/or growth in the matrix. In addition, when the mechanical behavior of collagen fibers is compared with mechanical data from mineralized turkey tendon, the results indicate that collagen fibril-to-fibril interactions present in turkey tendon appear to be more organized compared with self-assembled aligned collagen fibers. We concluded that organized collagen-collagen interactions appear to be an important characteristic required for elastic energy storage in tendon.

Animals↗

PubMed2004

Elastic energy storage in unmineralized and mineralized extracellular matrices (ECMs): a comparison between molecular modeling and experimental measurements.

In order to facilitate locomotion and limb movement many animals store energy elastically in their tendons. In the turkey, much of the force generated by the gastrocnemius muscle is stored as elastic energy during tendon deformation and not within the muscle. As limbs move, the tendons are strained causing the collagen fibers in the extracellular matrices to be strained. During growth, avian tendons mineralize in the portions distal to the muscle and show increased tensile strength, modulus, and energy stored per unit strain as a result. In this study the energy stored in unmineralized and mineralized collagen fibers was measured and compared to the amount of energy stored in molecular models. Elastic energy storage values calculated using the molecular model were slightly higher than those obtained from collagen fibers, but display the same increases in slope as the fiber data. We hypothesize that these increases in slope are due to a change from the stretching of flexible regions of the collagen molecule to the stretching of less flexible regions. The elastic modulus obtained from the unmineralized molecular model correlates well with elastic moduli of unmineralized collagen from other studies. This study demonstrates the potential importance of molecular modeling in the design of new biomaterials.

Animals↗

PubMed2004

Analysis of mineral deposition in turkey tendons and self-assembled collagen fibers using mechanical techniques.

During limb movement and locomotion, animals store elastic energy in the tendons of the feet, legs, and other limbs. In the turkey, much of the force generated by the gastrocnemius muscle during locomotion is stored as elastic energy through deformation of the tendon. During growth and development, the leg tendons in some avians, including turkeys, mineralize and result in an increase in tensile strength and modulus. The purpose of our study was to evaluate the effects of mineralization on elastic energy storage and transmission in turkey tendons. Elastic and viscous stress-strain curves and elastic energy storage behavior were used to compare the behavior of mineralized turkey gastrocnemius tendons and mineralized self-assembled type I collagen fibers. Based on analysis of these two systems, we concluded that a simple mineralized fibrillar collagenous substrate can mimic the behavior of a more complex fibrillar collagenous substrate such as mineralized turkey tendon; however, the exact mechanism of mineralization may be different between the two substrates. Changes in mechanical properties of turkey tendon were consistent with a model in which mineralization appears to increase the effective collagen fibril length by efficiently transferring stress between neighboring collagen fibrils. Mineralization in self-assembled collagen fibers increased elastic energy storage less efficiently as compared with turkey tendon suggesting that the noncollagenous components of mineralizing tissue may act to promote collagen fibril to collagen fibril interactions.

Animals↗

PubMed2003

Collagen self-assembly and the development of tendon mechanical properties.

The development of the musculoskeleton and the ability to locomote requires controlled cell division as well as spatial control over deposition of extracellular matrix. Self-assembly of procollagen and its final processing into collagen fibrils occurs extracellularly. The formation of crosslinked collagen fibers results in the conversion of weak liquid-like embryonic tissues to tough elastic solids that can store energy and do work. Collagen fibers in the form of fascicles are the major structural units found in tendon. The purpose of this paper is to review the literature on collagen self-assembly and tendon development and to relate this information to the development of elastic energy storage in non-mineralizing and mineralizing tendons. Of particular interest is the mechanism by which energy is stored in tendons during locomotion. In vivo, collagen self-assembly occurs by the deposition of thin fibrils in recesses within the cell membrane. These thin fibrils later grow in length and width by lateral fusion of intermediates. In vitro, collagen self-assembly occurs by both linear and lateral growth steps with parallel events seen in vivo; however, in the absence of cellular control and enzymatic cleavage of the propeptides, the growth mechanism is altered, and the fibrils are irregular in cross section. Results of mechanical studies suggest that prior to locomotion the mechanical response of tendon to loading is dominated by the viscous sliding of collagen fibrils. In contrast, after birth when locomotion begins, the mechanical response is dominated by elastic stretching of crosslinked collagen molecules.

Animals↗