Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.

Multiple Mode Vibration Suppression in Controlled Flexible Systems

Prior research has led to the development of input command shapers that can reduce residual vibration in single- or multiple-mode flexible systems. We present a method for the development of multiple-mode shapers which are simpler to implement and produce smaller response delays than previous designs. An MIT / NASA experimental flexible structure, MACE, is employed as a test article for the validation of the new shaping method. We examine the results of tests conducted on simulations of MACE. The new shapers are shown to be effective in suppressing multiple-mode vibration, even in the presence of mild kinematic and dynamic non-linearities.

Time-Frequency Representations for Speech Signals

This work addresses two related questions. The first question is what joint time-frequency energy representations are most appropriate for auditory signals, in particular, for speech signals in sonorant regions. The quadratic transforms of the signal are examined, a large class that includes, for example, the spectrograms and the Wigner distribution. Quasi-stationarity is not assumed, since this would neglect dynamic regions. A set of desired properties is proposed for the representation: (1) shift-invariance, (2) positivity, (3) superposition, (4) locality, and (5) smoothness. Several relations among these properties are proved: shift-invariance and positivity imply the transform is a superposition of spectrograms; positivity and superposition are equivalent conditions when the transform is real; positivity limits the simultaneous time and frequency resolution (locality) possible for the transform, defining an uncertainty relation for joint time-frequency energy representations; and locality and smoothness tradeoff by the 2-D generalization of the classical uncertainty relation. The transform that best meets these criteria is derived, which consists of two-dimensionally smoothed Wigner distributions with (possibly oriented) 2-D guassian kernels. These transforms are then related to time-frequency filtering, a method for estimating the time-varying 'transfer function' of the vocal tract, which is somewhat analogous to ceptstral filtering generalized to the time-varying case. Natural speech examples are provided. The second question addressed is how to obtain a rich, symbolic description of the phonetically relevant features in these time-frequency energy surfaces, the so-called schematic spectrogram. Time-frequency ridges, the 2-D analog of spectral peaks, are one feature that is proposed. If non-oriented kernels are used for the energy representation, then the ridge tops can be identified, with zero-crossings in the inner product of the gradient vector and the direction of greatest downward curvature. If oriented kernels are used, the method can be generalized to give better orientation selectivity (e.g., at intersecting ridges) at the cost of poorer time-frequency locality. Many speech examples are given showing the performance for some traditionally difficult cases: semi-vowels and glides, nasalized vowels, consonant-vowel transitions, female speech, and imperfect transmission channels.

The Effect of Transmission Design on Force-Controlled Manipulator Performance

Previous research in force control has focused on the choice of appropriate servo implementation without corresponding regard to the choice of mechanical hardware. This report analyzes the effect of mechanical properties such as contact compliance, actuator-to-joint compliance, torque ripple, and highly nonlinear dry friction in the transmission mechanisms of a manipulator. A set of requisites for high performance then guides the development of mechanical-design and servo strategies for improved performance. A single-degree-of-freedom transmission testbed was constructed that confirms the predicted effect of Coulomb friction on robustness; design and construction of a cable-driven, four-degree-of- freedom, "whole-arm" manipulator illustrates the recommended design strategies.

Residual Vibration Reduction in Computer Controlled Machines

Control of machines that exhibit flexibility becomes important when designers attempt to push the state of the art with faster, lighter machines. Three steps are necessary for the control of a flexible planet. First, a good model of the plant must exist. Second, a good controller must be designed. Third, inputs to the controller must be constructed using knowledge of the system dynamic response. There is a great deal of literature pertaining to modeling and control but little dealing with the shaping of system inputs. Chapter 2 examines two input shaping techniques based on frequency domain analysis. The first involves the use of the first deriviate of a gaussian exponential as a driving function template. The second, acasual filtering, involves removal of energy from the driving functions at the resonant frequencies of the system. Chapter 3 presents a linear programming technique for generating vibration-reducing driving functions for systems. Chapter 4 extends the results of the previous chapter by developing a direct solution to the new class of driving functions. A detailed analysis of the new technique is presented from five different perspectives and several extensions are presented. Chapter 5 verifies the theories of the previous two chapters with hardware experiments. Because the new technique resembles common signal filtering, chapter 6 compares the new approach to eleven standard filters. The new technique will be shown to result in less residual vibrations, have better robustness to system parameter uncertainty, and require less computation than other currently used shaping techniques.

Compliance and Force Control for Computer Controlled Manipulators

Compliant motion occurs when the manipulator position is constrained by the task geometry. Compliant motion may be produced either by a passive mechanical compliance built in to the manipulator, or by an active compliance implemented in the control servo loop. The second method, called force control, is the subject of this report. In particular, this report presents a theory of force control based on formal models of the manipulator, and the task geometry. The ideal effector is used to model the manipulator, and the task geometry is modeled by the ideal surface, which is the locus of all positions accessible to the ideal effector. Models are also defined for the goal trajectory, position control, and force control.