Engineering craniofacial scaffolds.

OBJECTIVE: To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. EXPERIMENTAL VARIABLE: Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. OUTCOME MEASURE: Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology. SETTING: Departments of Biomedical Engineering, Oral/Maxillofacial Surgery, and Oral Medicine, Pathology and Oncology at the University of Michigan. RESULTS: Results showed that the design/fabrication approach could create scaffolds with designed porous architecture to match craniofacial anatomy. These scaffolds could be fabricated from a wide range of biomaterials, including titanium, degradable polymers, and degradable calcium phosphate ceramics. Mechanical tests showed that fabricated scaffolds had compressive modulus ranging 50 to 2900 MPa and compressive strength ranging from 2 to over 56 MPa, within the range of human craniofacial trabecular bone. In vivo testing of designed scaffolds showed that they could support bone regeneration via delivery of BMP-7 transduced human gingival fibroblasts in a mouse model. Designed hydroxyapatite scaffolds with pore diameters ranging from 400 to 1200 microns were implanted in minipig mandibular defects for 6 and 18 weeks. Results showed substantial bone ingrowth (between 40 and 50% at 6 weeks, between 70 and 80% at 18 weeks) for all scaffolds, with no significant difference based on pore diameter. CONCLUSION: Integrated image-based design and solid free-form fabrication can create scaffolds that attain desired elasticity and permeability while fitting any 3D craniofacial defect. The scaffolds could be manufactured from degradable polymers, calcium phosphate ceramics and titanium. The designed scaffolds supported significant bone regeneration for all pore sizes ranging from 300 to 1200 microns. These results suggest that designed scaffolds are clinically applicable for complex craniofacial reconstruction.

Prototype theory and compositionality.

Osherson and Smith (1981, Cognition, 11, 237-262) discuss a number of problems which arise for a prototype-based account of the meanings of simple and complex concepts. Assuming that concept combination in such a theory is to be analyzed in terms of fuzzy logic, they show that some complex concepts inevitably get assigned the wrong meanings. In the present paper we argue that many of the problems O&S discovered are due to difficulties that are intrinsic to fuzzy set theory, and that most of them disappear when fuzzy logic is replaced by supervaluation theory. However, even after this replacement one of O&S's central problems remains: the theory still predicts that the degree to which an object is an instance of, say, "stripped apple" must be less than or equal to both the degree to which it is an instance of "striped" and the degree to which it is an instance of "apple", but this constraint conflicts with and the degree to which it is an instance of "apple", but this constraint conflicts with O&S's experimental results. The second part of the paper explores ways of solving this and related problems. This leads us to suggest a number of distinctions and principles concerning how prototypicality and other mechanisms interact and which seem important for semantics generally. Prominent among these are (i) the distinction between on the one hand the logical and semantic properties of concepts and on the other the linguistic that between concepts for which the extension is determined by their prototype and concepts for which extension and prototypicality are independent.