Functional Tissue Engineering Research

Mechanical Driving Force of Bone Adaptation to Mechanical Loading

To determine the state of equilibrium of engineering parameters that describe the

mechanical loading environment at the surface of human trabecular bone, vertebral bone

samples were scanned and numerically analyzed for a multitude of loading conditions.

Trabecular bone, the porous bone found in the spine, is known to be a mechanically sensitive, metabolic tissue. Despite years of knowledge regarding the adaptability of microarchitecture with mechanical loading, little is known regarding the control system of cell recruitment governing this activity. For many tissues (including bone) which are mechanically regulated, discovery of the driving forces behind tissue adaptation is the limiting factor in developing improved, 3-D cell tissue engineered constructs which resembles the morphology of the native tissue. With bone resportion and formation predominantly occurring at the bone surface, the question arises: ’ÄúWhat mechanical environment is present on the surface of trabecular bone (the location of the metabolic activity) to incite this mechano-sensitive tissue?’Äù In this study, finite element analyses were conducted on virtual bone cubes extracted from samples of human cadaveric vertebral bodies, in order to determine trends in the mechanical surface environment. By applying six different loading conditions onto these numerical models, the frequency profile of twelve engineering parameters were determined. The shapes of these mechanical profiles were then quantified with a metric representing ’Äòhow uniform the bone surface is’Äô and statistical comparisons were made between what could be the mechanical driving forces behind tissue adaptation to mechanical loading. The results are explained by an interesting theory: a control process which actively maintains a prescribed non-equilibrium. This is not unlike many biological processes such as transport pumps within the cell membrane, etc., which seeks to form a gradient (chemical, biological) through mechanical work. In the case of bone, however, the gradient itself may be mechanical in nature.

Computer Aided Tissue Engineering

Computer-Aided Tissue Engineering incorporates the fields of bio-modeling, biomimetic design

and bio-manufacturing to fabricate functional tissue on a patient specific basis. Most frequently,

medical imaging plus direct fabrication (e.g. rapid prototyping) is used for the fabrication.

Tissue engineering is developing into a less speculative science involving the careful interplay of numerous design parameters and multidisciplinary professionals. Problem solving abilities and state of the art research tools are required to develop solutions for a wide variety of clinical issues. One area of particular interest is orthopedic biomechanics, a field that is responsible for the treatment of over 700,000 vertebral fractures in the United States alone last year. Engineers are currently lacking the technology and knowledge required to govern the subsistence of cells in vivo, let alone the knowledge to create a functional tissue replacement for a whole organ. Despite this, advances in computer-aided tissue engineering are continually growing. Using a combinatory approach to scaffold design, patient-specific implants may be constructed. Computer-aided design, optimization of geometry using voxel finite element models or other optimization routines, creation
of a library of architectures with specific material properties, rapid prototyping, and determination of a defect site using imaging modalities highlight the current availability of design resources. This study proposes a novel methodology from start to finish which could, in the future, be used to design a tissue-engineered construct for the replacement of an entire vertebral body.

Tailored Drug Release through Targeted Porogen Design

Porogens can be easily fabricated using soft lithography techniques. Several thousand particles are

needed to fabricate samples large enough to represent clinical significant sizes. Depending on the

volume fraction of the porogens, only fractions of the porogens are actually released. Samples with an

initial porogen volume fraction of 60% or more released the most drugs.

Metastatic spinal cord cancers require tumor resection and compensation for the loss of structural integrity. Standard post-operative treatment is through systemic drug delivery and radiation, and implants for structural support of the remaining tissue to prevent fracture. These spinal tumors present clinical problems due to the relative paucity of effective adjuvant therapies, the extremely high propensity for local recurrence and the loss of spinal stability. We propose a course of investigation for the development of a tailorable drug delivery method based on transport and diffusion from materials already approved for clinical usage in humans. In this study, we assessed the drug release from a drug-laden composite cement. We hypothesize that the mechanical properties and the permeability of composite bone cements may be controlled through pore structure parameters of a particular composite, thereby allowing the drug release kinetics to be tailored without significant loss of mechanical integrity. Thus, we modulated drug release from composite cements through the variation of the surface area of the composite. The scaffolds were analyzed via microcomputed tomography for their morphological parameters. The results of this study demonstrate that a tailored drug release can be obtained through programmed variation of volume fraction and thus a tailored permeability can be obtained through modification of pore structural parameters. Introducing 60% porosity in the PMMA samples doubled the effective drug release. This study is the first step in the development of a composite cement delivery vehicle that offers mechanical reinforcement and localized, tailored drug release..