14 research outputs found
Dental Implant Systems
Among various dental materials and their successful applications, a dental implant is a good example of the integrated system of science and technology involved in multiple disciplines including surface chemistry and physics, biomechanics, from macro-scale to nano-scale manufacturing technologies and surface engineering. As many other dental materials and devices, there are crucial requirements taken upon on dental implants systems, since surface of dental implants is directly in contact with vital hard/soft tissue and is subjected to chemical as well as mechanical bio-environments. Such requirements should, at least, include biological compatibility, mechanical compatibility, and morphological compatibility to surrounding vital tissues. In this review, based on carefully selected about 500 published articles, these requirements plus MRI compatibility are firstly reviewed, followed by surface texturing methods in details. Normally dental implants are placed to lost tooth/teeth location(s) in adult patients whose skeleton and bony growth have already completed. However, there are some controversial issues for placing dental implants in growing patients. This point has been, in most of dental articles, overlooked. This review, therefore, throws a deliberate sight on this point. Concluding this review, we are proposing a novel implant system that integrates materials science and up-dated surface technology to improve dental implant systems exhibiting bio- and mechano-functionalities
Combinatorial and high-throughput methods for biomaterials synthesis and design
Combinatorial strategies have been developed to study the phase behavior of biodegradable polyanhydrides for drug and protein delivery applications. The polyanhydrides of interest are poly[1,6-bis(p-carboxyphenoxy) hexane] (CPH) and poly[sebacic anhydride] (SA). Both continuous and discrete polymer blend libraries were fabricated by using a combination of solution-based gradient deposition and rapid prototyping. Blend compositions were characterized via a unique high throughput transmission mode FTIR sampling technique and compared against theoretical mass balance predictions. To obtain phase diagrams of CPH/SA, the effect of blend composition and annealing temperature on the miscibility of the blend was studied. This gradient library was observed with optical microscopy in order to determine cloud points. These results were compared with SAXS studies on discrete libraries, which contained previously specified blend compositions and the agreement between the two methods was very good. The CPH/SA system exhibits upper critical solution temperature behavior
Novel Biofabrication Technologies to Recapitulate \u3ci\u3eIn Vivo\u3c/i\u3e Geometries in Collagen Hydrogels
Tissue engineering and regenerative medicine aims to restore form and function to tissues that have been lost or damaged due to disease, congenital defect, or trauma. Biomaterials suitable to restore these complex tissues need to provide a balance between chemical and mechanical properties, providing accurate cell-matrix interaction and induce in vivo behaviors such as proliferation, differentiation and migration. It also requires that physical and chemical cues be presented to the body in the proper temporal and spatial pattern. The extracellular matrix exerts forces that are transmitted through focal adhesion causing changes in the cell behavior. The hypothesis for this dissertation work was that by using the ideal substrate composition, the geometrical features and the proper elasticity of the substrate, we can recapitulate the microenviroments of the in vivo niche and control cell behavior. The self renewal capabilities of muscle stem cells, satellite cells, are lost once they are culture in a rigid environment where they commit to become skeletal myocytes. In our studies, we tuned the elasticity of a collagen hydrogel to their in vivo elastic modulus and we maintain the quiescence phenotype. We developed reaction electrospinning, which is a technique that combines two processes: electrospinning and fibrillogenesis. For the first time in literature, we show that as we spin collagen monomers and microfibrils using benign solvents, they undergo fibrillogenesis resulting in fibrous collagen scaffolds. Also, we developed a sacrificial material, BSA rubber, which can deliver specific geometrical templates to a collagen material, recapitulating the internal three-dimensional architectures. Our prototype consist of a 3D branched architecture using type I collagen. Overall, we developed fabrication techniques that allow us to tune the elasticity of the matrix, create fibrous scaffolds, and incorporate the geometrical features into an in vitro collagen scaffold. These techniques combine state of the art imaging, micromachining and selective enzymatic activity to create three dimensional biomaterials. The overall goal of this work is to fabricate custom made tissue scaffolds that replicate in vivo tissue composition, architecture, and cell population for broad application in tissue engineering. These new biomaterials will enable the modulation of cell potential, and thus, accelerate discovery in the field of regenerative medicine
Usinagem de próteses para cranioplastia a partir de imagens tomográficas
Orientador: Dalberto Dias da CostaDissertação (mestrado) - Universidade Federal do Paraná, Setor de Tecnologia, Programa de Pós-Graduação em Engenharia Mecânica. Defesa: Curitiba, 2004Inclui bibliografiaResumo: A fabricação de próteses para substituição de tecidos duros (ossos) tem sido um tema recorrente em diversos trabalhos científicos na área de bioengenharia. Recentemente, com o avanço das técnicas de digitalização e processamento de imagens, vários pesquisadores vêm defendendo o implante de próteses pré-fabricadas como uma alternativa para redução do tempo de cirurgia, da morbidade, da dor pós-operatória, do risco de infecções e rejeições, além de apresentar melhores resultados estéticos. Dentre as alternativas para a fabricação de próteses sob medida, destaca-se o uso das tecnologias CAD (Computer-Aided Design), CAM (Computer-Aided Manufacturing) e CNC (Comando Numérico Computadorizado). Entretanto, existem ainda alguns obstáculos, no que se refere à integração da informação (imagens) obtida por tomografia aos sistemas CAD/CAM/CNC comerciais. O objetivo deste trabalho é apresentar e discutir duas diferentes abordagens para essa integração e mostrar os resultados da fabricação, por usinagem, de uma prótese para fins médicos. Várias imagens tomográficas de um crânio humano seco foram utilizadas como fonte primária de informação. Utilizando-se tanto softwares dedicados ao processamento de informações médicas como os de uso geral, para conversão e vetorização de imagens, foi reconstruída uma região de interesse do crânio digitalizado. Essa região modelada foi avaliada e depois convertida em um formato apropriado aos sistemas CAM’s, os quais permitiram a simulação e geração de um programa CN para a usinagem de uma possível prótese dessa região. Esta prótese foi fresada em acrílico e depois inspecionada visual e dimensionalmente. A principal conclusão deste trabalho é que a usinagem direta propicia excelentes resultados estéticos enquanto alternativa para a fabricação de implantes para cranioplastia.
Palavras-chave: usinagem; superfícies complexas; imagens tomográficas; próteses sob medida; cranioplastia.ABSTRACT
The use of prosthesis, for replacement of hard tissues (bones), has been a recurrent subject in a huge variety of scientific works in the field of bioengineering. Lately, with the advancement in digitalizing and image processing, researchers have pointed out the application of pre-fabricated implants as an alternative way for reduction of the time, morbidity, postsurgery pain, the risk of infections and rejections, besides presenting better aesthetic results. Among the alternatives for tailored prosthesis, the technologies CAD (Computer-Aided Design), CAM (Computer-Aided Manufacturing) and CNC (Computerized Numeric Control) are mandatory. However, there are still some difficulties concerning the integration of the information acquired from CT images to the commercial CAD/CAM/CNC systems. The purpose of this research is to present and discuss two differents methodologies for this integration and show the machining results of a milled PMMA prosthesis. Several CT images of a dry human skull were taken as primary source of information. Specialized medical softwares and general purpose systems, for image processing, were evaluated as a two methods for vetorizing and 3D reconstruction of a separated region from the CT images. The modeled region was evaluated and converted to readable CAM formats for machining simulation and NC code generation for a similar prosthesis. An acrilic blank was milled according to planed prosthesis and visualy inspected and measured. The main conclusion of this work is concerned to the good aesthetic results obtained by direct machining for cranioplasty.
Keywords: Milling; sculptured surfaces; CT images; individual implants; cranioplasty
Self-Assembling Peptides for Cartilage Regeneration
Loss of glycosaminoglycans (GAGs) in osteoarthritic (OA) cartilage contributes to a decrease in mechanical properties and function in vitro, and is considered to be a major contributor to disease progression. The aims of this investigation were to test the hypothesis that a combination of self-assembling peptides (SAPs) and chondroitin sulfate (glycosaminoglycan; GAG) would restore the biomechanical properties of GAG depleted porcine condylar cartilage, ideally to a level intrinsic to native porcine condylar cartilage.
The SAPs investigated were members of the P11 series which have been designed to spontaneously self-assemble into three-dimensional fibrilar hydrogels, in response to physiological conditions. Initial studies were carried out to determine which of three peptides (P11-4, P11-8 and P11-12) demonstrated high β-sheet percentage, long-woven fibrilar networks and high stiffness; when mixed with chondroitin sulfate at two different GAG molar ratios (1:16 and 1:64) in physiological conditions, using FTIR analysis, transmission electron microscopy and rheology. The β-sheet percentage, dimensions of fibrils and stiffness were dependent upon the peptide, GAG molar ratio and Na2+ salt concentration. P11-4 and P11-8: GAG mixtures had high β-sheet percentage ranging from 50.6-91 % and 81.7-92 %, respectively. Fibril lengths of the P11-4 and P11-8: GAG mixtures were in the range 498- 3518 nm and the elastic shear modulus (G’) ranged from 4,479-10,720 Pa and 7,722-26,854 Pa, respectively. P11-4 and P11-8: GAG mixtures were selected for further investigation.
In order to produce a GAG depleted cartilage model, porcine femoral condylar cartilage was subjected to three different methods of GAG depletion (1) coating the surface with chondroitinase ABC (2) injecting chondroitinase ABC into the cartilage (3) washing the condyles in sodium dodecyl sulfate (SDS). GAG depletion was successfully achieved following two 24 hour washes in 0.1 % (w/v) SDS and buffer washes. Histological analysis of safranin O stained sections revealed an absence of GAGs. Quantification of GAGs using the dimethylemethylene blue assay revealed that 75 % of GAGs had been removed.
In order to assess the effects of peptide: GAG mixtures on the biomechanical properties of the GAG depleted porcine condylar cartilage a biomechanical test method was developed. A series of indentation tests using different loads, followed by finite element analysis of the data were performed on native and GAG depleted porcine condylar cartilage; to identify a suitable load for detection of a significant difference in the deformation, equilibrium elastic modulus and permeability between the native and GAG depleted porcine condylar cartilages. A load of 0.31 N was identified as the most appropriate.
GAG depleted porcine condylar cartilage was injected with P11-4 and P11-8 alone, P11-4 and P11-8 : GAG mixtures at a molar ratio of 1:64 and chondroitin sulfate alone. The average percentage deformation of the medial condylar cartilage samples injected with P11-4 alone and P11-4: GAG mixture was 15.5 % and 8.7 % and for P11-8 alone and P11-8: GAG mixture was 11.4 % and 9.1 % respectively; compared to 6.3 % for the native cartilage and 12.6 % for the GAG depleted cartilage. The average equilibrium elastic modulus of the medial cartilage samples injected with P11-4 alone and P11-4: GAG mixture was 0.16 MPa and 0.43 MPa and for P11-8 alone and P11-8: GAG, 0.23 MPa and 0.35 MPa, respectively; compared to 0.49 MPa for the native cartilage and 0.21 MPa for the GAG depleted cartilage. Statistical analysis (ANOVA) showed that a mixture of P11-4: GAG, but not P11-8: GAG restored both the percentage deformation and equilibrium elastic modulus of the GAG depleted cartilage to levels that were not significantly different to the native cartilage.
This study has shown that the use of P11-4 in combination with chondroitin sulfate has future potential for development as a minimally invasive treatment for early stage osteoarthritis
In vitro models for cartilage engineering using primary cells and biodegradable scaffolds
Tese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células EstaminaisCartilage tissue engineering investigation has been developing strongly in the last
years. The main difficulty in cartilage regeneration is its restricted self-repair capacity.
Thus, investigation has been focused in promoting the regeneration of functional
tissues. There are already products in the market using tissue engineering concepts to
promote cartilage regeneration. The results of these treatments, although positive, still
need improvements. Current treatments with joint implants are not long lasting and
frequently require revision. Tissue engineering thus may provide different solutions
based on tissues repair, contrarily to substitution by joint implants.
This thesis comprises the investigation of three in vitro models aiming to produce
cartilage extracellular matrix (ECM), using primary cultures and scaffolds as supports
for cell growth and ECM deposition. The scaffold is one of the key points in a tissue
engineering strategy, thus several morphologies and formulations based on
biodegradable scaffolds were explored herein. Moreover, different culture conditions
were also investigated, either by using dynamic cultures (stirred and flow perfusion) or
static cultures. Therefore, the thesis is divided in 3 sections concerning each of the in
vitro models tested and cells used: bovine articular chondrocytes (BAC), human bone
marrow derived mesenchymal stem cells (hBMSCs), and co-cultures of human primary
culture of articular chondrocytes (hACs) and MSCs.
The first studies of this thesis were developed with BACs using two types of
electrospun scaffolds: polycaprolactone (PCL) and starch compounded with PCL
(SPCL) nanofiber meshes and microporous scaffolds. Those were composed by a blend
of chitosan-poly(butylene succinate) (CPBS) with two different pore sizes and
morphologies. Overall, we concluded that BAC model allowed the production of
cartilage ECM on all tested scaffolds. For electrospun nanofiber meshes, no significant
differences were found between PCL and SPCL as supports for the cells in terms of
ECM deposition. However, results were positive in terms of the matrix deposition in
both substrates. Concerning CPBS scaffolds, 80 CPBS formulation presenting larger
pores with random distribution proved to have a stronger performance when compared to 60 CPBS formulation. Those results showed the importance of larger pores for cells
to colonize the scaffolds structure and deposit ECM.
In our second model we studied the chondrogenic differentiation of hBMSCs when
cultured onto nanofibers (PCL) or chitosan-based microfiber meshes, using an in house
developed flow perfusion bioreactor. Human MSCs were able to grow and differentiate
when cultured either seeded in electrospun nanofiber meshes or in microfiber meshes.
The use of dynamic culture with nanofiber meshes did not provide solid evidences of an
enhancement of hBMSCs chondrogenic differentiation. Conversely, microfiber meshes
indeed showed being adequate for this type of culture, as chondrogenic differentiation
was enhanced when hBMSCs were seeded and cultured on those scaffolds in the
bioreactor, compared to the static control. The results may even be further enhanced by
the optimization of the flow rate used in those experiments.
Finally, co-cultures using hACs and hMSCs seeded onto chitosan-based microfiber
meshes were established. We selected two different sources of hMSCs (hBMSCs or
human Wharton´s jelly mesenchymal stem cells - hWJSCs) and compared their
chondrogenic potential when co-cultured in direct contact with hACs, or indirectly cocultured
with conditioned medium derived from hACs cultures. Results showed that
indirect co-cultures using conditioned medium promoted more cartilage ECM
formation, both with hBMSCs or with hWJSCs. Additionally, hWJSCs demonstrated a
higher chondrogenic potential than hBMSCs that produced an ECM containing higher
expression levels of collagen type I. This result is very interesting because it is believed
that has a higher potential to be used in clinic to treat patients, since unrelated
chondrocytes may be used to induce the chondrogenic differentiation of autologous
adult stem cells.
Overall, the work on this thesis presents some valid concepts for cartilage tissue
engineering. We were able to obtain cartilage like tissue using primary cultures, either
differentiated or undifferentiated. Deposition of cartilage ECM was observed in all the
tested 3D biodegradable scaffolds either in static or in dynamic culture conditions. The
advantages of co-culturing differentiated and undifferentiated cells for cartilage
engineering were also demonstrated.A investigação em engenharia de cartilagem teve um desenvolvimento muito intenso nos
últimos anos. Uma das maiores dificuldades em regenerar cartilagem prende-se com o facto de
este tecido ter uma capacidade de auto-regeneração muito limitada. Actualmente, já existem no
mercado alguns produtos para a regeneração de tecido cartilagíneo, baseados em conceitos de
engenharia de tecidos. Apesar de trazerem resultados positivos, estes tratamentos ainda
necessitam de ser muito optimizados. A aplicação actual de implantes para recuperar a
funcionalidade das articulações não é duradoura, e frequentement os implantes necessitam de
revisão após alguns anos. A engenharia de tecidos pode desenvolver soluções mais duradouras,
baseadas na regeneração de tecidos e não na substituição da área afectada por implantes
articulares.
Esta tese engloba o estudo de três modelos in vitro desenvolvidos com o objectivo de produzir
matriz extracelular de cartilagem (ECM), utilizando culturas celulares primárias e “scaffolds”
como suportes para o crescimento das células e deposição da referida matriz. O “scaffold” é um
dos aspectos críticos numa estratégia de engenharia de tecidos, por isso vários “scaffolds”
biodegradáveis com morfologias e formulações diferentes foram avaliados. Várias condições de
cultura foram também investigadas, usando culturas dinâmicas (agitação ou fluxo de perfusão)
ou estáticas. Consequentemente, a tese está dividida em três secções correspondentes a cada um
dos modelos in vitro testados, e agrupados segundo o tipo de células utilizadas: condrócitos
articulares bovinos (BAC), células estaminais mesenquimais derivadas de medula óssea
(hBMSCs) e co-culturas de células primárias humanas: condrócitos articulares (hACs) e células
estaminais mesenquimais (hMSCs).
Os primeiros estudos apresentados nesta tese foram desenvolvidos com BACs e dois tipos de
malhas de nanofibras: nanofibras de policaprolactona (PCL) ou de amido composto com
policaprolactona (SPCL), e também com um “scaffold” com microporosidade. Estes últimos
“scaffolds” foram produzidos com uma mistura de quitosano e de polibutileno succinato
(CPBS), apresentando dois tamanhos de poros características e morfologias diferentes. Em
geral, concluimos que o modelo com BACs permitiu a produção de ECM em todos os
“scaffolds” e malhas de nanofibras testados. Não foram observadas diferenças significativas em
termos de deposição de ECM entre as malhas de PCL e de SPCL. No entanto, os resultados
foram considerados positivos, pois houve deposição de ECM em ambos os substratos. No que diz respeito aos “scaffolds” de CPBS, a formulação 80 CPBS (com poros maiores de
distribuídos aleatoriamente) demonstrou um desempenho biológico mais expressivo quando
comparada com a formulação 60 CPBS. Estes resultados mostraram a importância de poros de
maior tamanho na estrutura dos “scaffolds” para facilitar a colonização celular e a deposição de
ECM.
O segundo modelo explorado é referente ao estudo da diferenciação condrogénica de
hBMSCs cultivadas em malhas de nanofibras (PCL) ou de microfibras (formadas por misturas
de quitosano), usando para tal um bioreactor de perfusão desenvolvido pelo nosso grupo.
Observou-se crescimento e diferenciação das células cultivadas quer nas malhas de nanofibras,
quer nas malhas de microfibras. A cultura dinâmica não evidenciou facilitar a diferenciação
condrogénica das hBMSCs. Por outro lado, foi demonstrado que as malhas de microfibras são
adequadas para este tipo de culturas dinâmicas, pois a diferenciação condrogénica foi
potenciada nas culturas destes “scaffolds” no bioreactor, comparativamente com os controlos
estáticos. Estes resultados poderão ainda vir a ser melhorados através da optimização das
condições de fluxo de meio de cultura utilizadas nestas experiências.
Finalmente, realizaram-se co-culturas de hACs e hMSCs em malhas de microfibras. Foram
seleccionados dois tipos de hMSCs: hBMSCs ou células estaminais mesenquimais derivadas da
geleia de Wharton (hWJSCs). Comparou-se o potencial condrogénico dos dois tipos de células
estaminais quando co-cultivadas em contacto directo com hACs, ou em contacto indirecto,
usando para tal meio condicionado proveniente das culturas de hACs. Os resultados
demonstraram que as culturas indirectas com meio condicionado promoveram uma maior
formação de ECM, usando quer hBMSCs, quer hWJSCs. Adicionalmente, as hWJSCs
revelaram um potencial condrogénico mais elevado do que as hBMSCs, que produziram uma
ECM rica em colagénio tipo I. O resultado com os meios condicionados é muito interessante
porque consideramos que poderá ter um elevado potencial para futuras aplicações clínicas. A
utilização de condrócitos heterólogos para obtenção de meios condicionados que promovam a
diferenciação condrogénica de células estaminais autólogas parece-nos importante no contexto
da engenharia de tecidos da cartilagem.
O trabalho apresentado nesta tese revelou alguns conceitos válidos para a engenharia de
cartilagem. Obteve-se tecido cartilagíneo usando quer culturas primárias de células
diferenciadas, quer de células indiferenciadas. A deposição de ECM ocorreu em todos os
“scaffolds” 3D biodegradáveis testados, quer em condições estáticas, quer em condições
dinâmicas. Por fim, demonstraram-se também algumas vantagens relativas à utilização de coculturas
de células diferenciadas com células indiferenciadas para a engenharia de tecidos de
cartilagem
AUGMENTED REALITY AND INTRAOPERATIVE C-ARM CONE-BEAM COMPUTED TOMOGRAPHY FOR IMAGE-GUIDED ROBOTIC SURGERY
Minimally-invasive robotic-assisted surgery is a rapidly-growing alternative to traditionally open and laparoscopic procedures; nevertheless, challenges remain. Standard of care derives surgical strategies from preoperative volumetric data (i.e., computed tomography (CT) and magnetic resonance (MR) images) that benefit from the ability of multiple modalities to delineate different anatomical boundaries. However, preoperative images may not reflect a possibly highly deformed perioperative setup or intraoperative deformation. Additionally, in current clinical practice, the correspondence of preoperative plans to the surgical scene is conducted as a mental exercise; thus, the accuracy of this practice is highly dependent on the surgeon’s experience and therefore subject to inconsistencies.
In order to address these fundamental limitations in minimally-invasive robotic surgery, this dissertation combines a high-end robotic C-arm imaging system and a modern robotic surgical platform as an integrated intraoperative image-guided system. We performed deformable registration of preoperative plans to a perioperative cone-beam computed tomography (CBCT), acquired after the patient is positioned for intervention. From the registered surgical plans, we overlaid critical information onto the primary intraoperative visual source, the robotic endoscope, by using augmented reality. Guidance afforded by this system not only uses augmented reality to fuse virtual medical information, but also provides tool localization and other dynamic intraoperative updated behavior in order to present enhanced depth feedback and information to the surgeon. These techniques in guided robotic surgery required a streamlined approach to creating intuitive and effective human-machine interferences, especially in visualization.
Our software design principles create an inherently information-driven modular architecture incorporating robotics and intraoperative imaging through augmented reality. The system's performance is evaluated using phantoms and preclinical in-vivo experiments for multiple applications, including transoral robotic surgery, robot-assisted thoracic interventions, and cocheostomy for cochlear implantation. The resulting functionality, proposed architecture, and implemented methodologies can be further generalized to other C-arm-based image guidance for additional extensions in robotic surgery
Design of low density bio-inspired structures
This study involves the development of novel methods to enhance structural efficiency in the development of high performance lightweight stiff metal mechanical components. Optimised designs are created from biologically-inspired templates, taking advantage of new additive manufacturing techniques which enable the realisation of more complex shapes.
The study focuses on the numerical side of design development and evaluation. Two case studies of aerospace components are considered: first, of an aircraft engine nacelle and second, of turbine blisks.
In the first study, rib stiffeners, based on fibre arrangement in plant stem cells, are introduced and their geometric features are optimised for mass minimisation with mechanical response constraints done via genetic algorithms coupled with finite element analysis. The displacements of the optimised nacelle are lower compared to the original. Mass has lower optimisation emphasis, thus final values approach the mass limit. Optimised designs from different loading cases and magnitudes thereof have similar physical features.
In the second study, turbine blisks are redesigned with an internal foam structure based on cancellous bones. Optimised 3D foam blisks are developed evaluated against the original solid design and with a different foam type. A study undertaken on 2D foam discs under inertial load demonstrates that foam configuration and densification methods influence the mechanical responses.
The thesis shows that viable biologically-inspired designs can be developed using optimisation techniques. In both cases remarkable mass reduction is achieved while remaining within mechanical constraints. The Pareto front is traced on the design space from optimisation results, representing the set of optimal designs rather than a single unique solution. In the nacelle the displacement contour heavily influences the rib layout, which prefers intersections at boundary condition sites. The weight-to-displacement ratios of bio-inspired designs are lower than in equivalent topologically-optimised ones. In the turbine blisk, foam stiffness under inertial load is found to increase with node connectivity. Increasing relative density increases stresses but decreases displacement, and the specific behaviour is influenced by the method in varying density. In 3D the resulting foam blisks have higher stresses and displacement than the solid one, but their weight-to-displacement ratio can be improved using high-connectivity foams
National Educators' Workshop. Update 92: Standard Experiments in Engineering Materials Science and Technology
This document contains a collection of experiments presented and demonstrated at the workshop. The experiments related to the nature and properties of engineering materials and provided information to assist in teaching about materials in the education community