Tendons transfer forces from muscle to bone and allow the locomotion of the body. However, tendons, especially for tendons in the hand, get lacerated commonly in different injuries and the healing of tendon within the narrow channel in the hand will normally lead to tendon adhesion and sacrificed tendon mechanics. Researches have been focused on addressing tendon adhesion prevention but neglecting healed tendon mechanics. This thesis discusses the principles and challenges in the design of biomaterials regarding flexor tendon repair with advanced polymer chemistry and materials science. A rational platform, not only focusing on the prevention of tendon adhesion, but devoting more efforts on final healed properties of tendons via implementing glycopolymer-based materials to guide tendon cells attachment, was designed, fabricated and characterized. Controlled ring opening polymerizations and atom transfer radical polymerizations were combined for the synthesis of miktoarm well-defined block copolymers. Para-fluorine click reactions were then implemented to afford glycopolymers with glucose units. Obtained copolymers were transformed into 3D membranes constituting a porous fibrous structure utilizing electrospinning. The aligned structure was then fabricated to optimize the mechanics of these materials for practical application as well as reconstruct normal tendon physiological structure. Lastly, the toxicity, cell affinity and cell activity of obtained materials were evaluated in vitro employing tendon cells as a cell line to confirm the suitability of obtained platforms for flexor tendon repair.

The field of biomaterials has seen huge development over the past decade with enormous efforts invested in discovering materials with improved biocompatibility, application and versatility. Polymers can display many properties that make them ideal biomaterials, such as their potential flexibility, low weight, low cost and biodegradability. Moreover, they can be prepared in a wide variety of compositions and forms and be readily fabricated into various shapes and structures. Polymer microarrays represent an efficient high-throughput platform for the screening and discovery of new materials compared to conventional assays with advantages such as high-density screening, internal consistency of assays and the requirement for only small quantities of material. The first part of this thesis describes work in the area of diabetes research with a focus on how dysfunctional β-cells could be replaced by the transplantation of β-cells obtained from pluripotent stem cells. To achieve this aim, high numbers of β-cells are required. A polymer microarray screening approach was used to identify a number of polymers that promoted the attachment of pancreatic progenitor cells and enhanced cell proliferation. Multiple scale-up fabrication techniques were assessed to establish the most suitable approach and surface for long term cell culture leading to the obtainment of reproducible in situ polymerised polymer layers with enhanced binding properties toward pancreatic progenitor cells. These surfaces have the potential to support cell adhesion and proliferation and could find potential use in the industrial sector to increase the production of pancreatic progenitor cells in vitro. In the second part, efforts were made to gain a better understanding of the maturation of β-cells and their behaviour, with the development of 3D hydrogels based on the previously identified polymers. In this scenario, parameters such as stiffness and porosity were evaluated to identify the best environmental conditions to support 3D cell culturing of pancreatic progenitor cells. Several approaches were tested to generate scaffolds with suitable stiffness and porosity leading to the obtainment of scaffolds based on the previously identified polymer composition and with controlled porosity and stiffness. These scaffolds could represent a suitable environment to allow a better understanding of cell organisation and regulation. In a third avenue of work, arrays of 3D biocompatible materials, which were tailored for varying elasticity, hardness, and porosity (to provide the necessary physical cues to control cellular functions) were fabricated. In this chapter, details of the development of an array of eighty 3D double-network hydrogel features are reported. The array features can be produced as single or double networks and modulated in terms of stiffness, viscoelasticity and porosity to assess cell response to materials with a wide range of properties. The final part of the thesis describes the development and screening of polymeric materials to allow a better understanding of cell–surface interactions with various cell types. To investigate the correlation between cell attachment and the nature of the polymer, a series of random and block copolymers were synthesised and examined for their abilities to attach and support the growth of human cervical cancer cells (HeLa) and human embryonic kidney cells (HEK293T), with attachment modelled on monomer ratios, arrangement, and polymer chain length. The results of this screening showed differences between block copolymers and random copolymers in cell adhesion and provide interesting insight into the improvement of polymer coatings for cell culture.

Made available in DSpace on 2014-06-11T19:31:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-07-21Bitstream added on 2014-06-13T19:01:11Z : No. of bitstreams: 1 tavares_hs_dr_araiq.pdf: 10653888 bytes, checksum: 02427dde51626e81dc6a99fe9d6b5cf1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Superfícies de titânio apresentam importantes propriedades físico-químicas e morfológicas com aplicações em muitos dispositivos que requerem interação com o tecido ósseo. O objetivo do presente estudo foi avaliar in vitro utilizando-se cultura de células estaminais a interação da superfície de titânio irradiado com laser em menor fluência (L1); laser com maior fluência (L2) e superfície L2 com recobrimento de apatitas, (HA). A irradiação laser Yb:YAG em diferentes parâmetros ocasionou a formação de óxidos de titânio nas superfícies irradiadas, que podem influenciar diretamente a integração biológica. As superfícies obtidas foram caracterizadas por Microscopia Eletrônica de Varredura (MEV) e Difração de raios X (DRX) e a camada de hidroxiapatita foi avaliada por espectroscopia no infra vermelho transformada de Fourier (FTIR) e medidas de ângulo de contato. As avaliações in vitro foram realizadas utilizando as superfícies L1, L2 e HA diretamente em contato com células humanas indiferenciadas. Os parâmetros biológicos avaliados foram: adesão, proliferação, e metabolismo celular. Foi determinada a concentração de fosfatase alcalina (ALP) e conteúdo total de proteína, produção de osteocalcina e diferenciação osteogênica pela associação das análises. A morfologia celular foi avaliada por MEV, e a micro análise por espectroscopia por energia dispersiva de raios X (EDS) e microscopia de fluorescência. Os resultados indicaram que todos os grupos experimentais apresentaram menor adesão e proliferação celulares nos estágios iniciais em relação ao grupo controle, com aumento da proliferação após 14 dias. Também aos 14 dias houve aumento na taxa de metabolismo celular em todos os grupos experimentais. Os níveis de ALP/Proteína associados aos dados sobre metabolismo celular indicaram sinais bioatividade do grupo HA aos 21 dias. Conclusão:.. / Titanium surfaces have important physical-chemistry and morphological properties with many applications on biomedical devices whose have bone tissue interaction. The laser beam irradiation on titanium surfaces presented in this study was evaluated by the osseointegration of human mesenchymal stem cells. In this study was performed laser irradiation (Low fluency L1; high fluency L2; high fluency associated apatite treatment HA; and the control group machined surface). The laser irradiated structures were initially characterized by Scanning Electronic Microscopy (SEM) and x ray diffraction (DRX) the HA group was subjected apatites treatment following the characterization by DRX, contact angle measurements and Infra red spectroscopy. The biological evaluations were performed by primary culture and differentiation of human stem cell. The parameters of in vitro evaluations were: Cell adhesion and proliferation by DNA quantification, cell metabolism, and cell morphology by SEM and fluorescence microscopy. The osteogenic differentiation was determined by ALP/Osteocalcin levels associated with SEM-EDS comparison. Results: All the experimental groups show less cell adhesion and proliferation at the initial stage of experiments than control group between 1 - 7 days. After 7 days the proliferation and cell metabolism increase on all experimental groups. The SEM micrographies associated with ALP/osteocalcin levels showed significant osteogenic differentiation on L1 group with significance differences of ALP/protein levels at day 7 (P<0.05), in addition, the HA group shows high levels ALP/Protein at 21 days. Conclusion: The laser beam irradiation process presented is clean, rapid and easy way to obtain a layer of oxides with micro and nanostructures. The best performance was found for L1 group with significant levels of osteocalcin and associated with morphological comparison, all experimental groups... (Complete abstract click electronic access below)

En ingénierie tissulaire, la survie in vivo de cellules souches implantées au sein d’un biomatériau est limitée par les conditions d’un environnement ischémique qui se caractérise par un déficit en oxygène et en nutriments. Récemment, dans le cadre d’un projet de recherche dédié au développement d’un hydrogel composite à base de fibrine, biomatériau conçu pour améliorer la survie de cellules souches post-implantation, il a été mis en évidence la nécessité de contrôler dans le temps et l’espace la disponibilité du glucose au sein de ce matériau. Cet apport in situ de glucose est réalisé par dégradation contrôlée de l’amidon, un polymère de glucose. Cette production est assurée par action enzymatique d’un catalyseur spécifique de l’hydrolyse de l’amidon, l’amyloglucosidase (AMG).Toutefois, il convient de maitriser différents paramètres tels que la fuite de l’AMG en dehors de l’hydrogel ou encore sa perte d’activité au cours du temps. Dans ce contexte, l’encapsulation de l’AMG dans des nanoparticules d’un polymère biodégradable et biocompatible, ici l’acide poly(lactique-co-glycolique) (PLGA), devrait permettre le contrôle des paramètres susmentionnés.Des nanoparticules de type core-shell contenant l’AMG (NPe) ont été synthétisés par l’adaptation d’un protocole de double émulsion (water-oil-water). Différentes méthodes ont été développées pour déterminer les propriétés physico-chimiques et biochimiques des nanoparticules produites. Le protocole de synthèse a été optimisé afin de produire des nanoparticules reproductibles et stériles utilisables dans des hydrogels implantables in vivo.Le cahier des charges de l’hydrogel enrichi en amidon et en NPe impose un apport continu du glucose pendant 1 mois. La stabilité des nanoparticules a été étudiée en solution et dans les hydrogels. La production de glucose grâce à ces NPe a été investiguée en solution et en hydrogel mettant en avant l’intérêt de ces nanoparticules au sein du dispositif. / In tissue engineering, the in vivo survival of stem cells located within a biomaterial is limited by an ischemic environment characterized by a low supply of oxygen and nutrients. Recent studies on fibrin based hydrogels (designed to improve stem cells survival after implantation) have highlighted the need to control the spatiotemporal availability of glucose within a biomaterial scaffold. Glucose release occurs through the degradation of starch, a glucose polymer, at a rate controlled by the action of the enzyme amyloglucosidase (AMG), a specific catalyst for the hydrolysis of starch.In order to eventually be of clinical impact, critical parameters must be tuned, such as the AMG leakage outside the hydrogel and its loss of activity over time. In this context, AMG encapsulation within nanoparticles of a biodegradable and biocompatible polymer, here poly(lactic-co-glycolic acid) (PLGA), is a promising means toward controlling the above parameters.The AMG-containing core-shell type nanoparticles (NPe) were synthesized by an adaptation of the double emulsion technique (water-oil-water). Different methods have been developed to determine the physicochemical and biochemical properties of the resulting nanoparticles. The synthesis was optimized to produce sterile and reproducible nanoparticles appropriate for in vivo implantable hydrogels.Nanoparticle stability and glucose release were investigated in solution and in hydrogels. A key specification of the hydrogel system, enriched in starch and NPe, is the continuous supply of glucose over 1 month. Glucose production was observed to meet this specification, highlighting the potential advantages of this approach.

Neste trabalho foi desenvolvido um estudo com o poliéster biodegradável P[3HB] (poli[R-3-hidroxibutirato]) e seu copolímero P[3HB-co-3HV] (poli[R-3-hidroxibutirato-co-3- hidroxivalerato]). Esses materiais são conhecidos por seu grande potencial de biodegradabilidade, porém sua utilização pela indústria ainda é limitada em função de seu baixo desempenho mecânico. Visando a tenacificação desses materiais, optou-se por misturá-los com os elastômeros EPDM (terpolímero de etileno-propileno-dieno) e PVB (Poli(vinil butiral)). Foram estudados quatro grupos de blendas: P[3HB]/EPDM e P[3HB-co- 3HV]/EPDM processados em misturadores internos e posteriormente prensadas em filmes; P[3HB]/EPDM e P[3HB]/PVB extrudados e posteriormente injetados. As blendas foram obtidas nas concentrações de 10, 20 e 30% em peso de elastômeros. Inicialmente, estudou-se efeito da incorporação de elastômeros na cristalinidade, estrutura cristalina, propriedades térmicas e dinâmico-mecânicas das matrizes, e o efeito do tipo de processamento utilizado. Observou-se que a adição dos elastômeros às matrizes semicristalinas aumentou a nucleação de esferulitos, resultando em um aumento da cristalinidade das mesmas. O PVB apresentou um efeito plastificante na estrutura do PHB. Os filmes apresentaram uma degradação térmica maior que as amostras injetadas, resultando em uma cristalização mais lenta e um grau de cristalinidade maior. Em um outro estudo, avaliou-se a morfologia, tensão interfacial, comportamento reológico, propriedades mecânicas e a biodegradabilidade das amostras estudadas. Foi observada uma morfologia de dispersão de gotas para todas as misturas, exceto para a mistura P[3HB]/EPDM obtida por injeção que apresentou um certo grau de co-continuidade. No caso das misturas injetadas foi visto que o fator que parece influenciar mais fortemente em sua morfologia final são as razões de viscosidade observadas entre a matriz e a fase dispersa das mesmas. A adição de elastômeros aumentou a resistência ao impacto do P[3HB], principalmente no caso da mistura P[3HB]/EPDM, o que pode estar relacionado à morfologia co-contínua observada nesta blenda. A incorporação dos elastômeros resultou em uma redução do módulo de elasticidade e da resistência à tração do P[3HB], e aumento do alongamento, principalmente no caso da mistura com PVB. Foi visto que a biodegradação do P[3HB] e P[3HB-co-3HV] aumentou com a adição de elastômeros, devido à morfologia de dispersão e a diminuição do tamanho dos esferulitos que aumentam a área interfacial para a ação das enzimas, facilitando a biodegradação. / In this work a study with the biodegradable polyester P[3HB] (poly[R-3- hydroxybutyrate]) and its copolymer P[3HB-co-3HV] (poly[R-3-hydroxybutyrate-co-3- hydroxyvalerate]) was conducted. These materials are known for their high biodegradability but their use is still limited because of their poor mechanical properties. In order to improve these properties it was chosen to blend these biodegradable polymers with EPDM (Ethylene propylene diene monomer) and PVB (Polyvinyl butyral). Four groups of blends were obtained: P[3HB]/EPDM and P[3HB-co-3HV]/EPDM blends were prepared using an internal mixer and then compressed molded; P[3HB]/PVB and P[3HB]/EPDM blends were prepared using an extruder and further injected. The blend concentrations ranged from 10 to 30 wt. % of the rubbery phase. Initially, the effect of rubber type on the crystallinity, the crystalline structure, thermal and dynamic-mechanical properties of the matrices and the effect of processing method to obtain the blends were investigated. The addition of elastomers on P[3HB] (and P[3HB-co- 3HV]) increases the nucleation, resulting in an increase of matrix crystallinity. PVB showed a plasticizing effect on the P[3HB] structure. Film samples showed a higher thermal degradation than injected ones, resulting in a slower crystallization and higher crystallinity. The morphology, interfacial tension, rheological behavior, mechanical properties (tensile and impact) and biodegradability of samples were also studied. A droplet dispersion morphology type was obtained for all the blends except for P[3HB]/EPDM injected samples which presented some extent of degree of continuity. The experimental results indicated that the final morphology observed for the blends was controlled by the viscosity ratio between the matrix and dispersed phase. Elastomer addition increased P[3HB] impact strength mainly for P[3HB]/EPDM blends, probably due to its co-continuous morphology. Moreover, elastomer incorporation resulted in a decrease of P[3HB] elastic moduli and tensile strength and increase of elongation of break, mainly for P[3HB]/PVB blends. It was observed that P[3HB] and P[3HB-co-3HV] biodegradation increased with elastomer addition due to the droplet dispersion morphology and decrease of spherulites size witch causes an increase of interfacial area for enzymes, facilitating biodegradation.

A quitosana é um biopolímero estudado em diversas áreas, tais como, ambiental, alimentícia, farmacêutica, biomédica e biotecnológica. Ela pode ser obtida de diferentes formas polimórficas de quitina, dentre as quais a forma &beta; tem se mostrado vantajosa, pois favorece modificações químicas mais homogêneas e leva a um produto final menos alergênico. A quitosana pode ser combinada com outros compostos a fim de interagir e/ou reagir com eles e modificar suas propriedades. O objetivo deste trabalho foi estudar como uso de ácido adípico, em substituição ao acético, afeta as propriedades de géis e esponjas de quitosana e de quitosana/gelatina, que foram posteriormente reticuladas com os agentes reticulantes EDC/NHS. As técnicas utilizadas para os estudos foram: reologia, FTIR, MEV, absorção em PBS e ensaios de citotoxicidade. Por reologia, observou-se que o aumento na concentração dos géis de quitosana tornou os géis mais elásticos e viscosos. O mesmo ocorreu na presença de gelatina ou EDC/NHS. O efeito do uso de ácido adípico em substituição ao acético também foi mostrado nos ensaios reológicos, pois os géis com 2% de quitosana e com quitosana/gelatina sem EDC/NHS se mostraram mais elásticos e mais viscosos quando o ácido adípico foi usado. Os espectros FTIR mostraram a presença de interações entre a quitosana e a gelatina e a formação de ligações amidas II após reticulação com EDC/NHS. Na preparação das esponjas observou-se que os géis de quitosana em ácido adípico geravam esponjas instáveis que se desfizeram durante a neutralização, mas essa instabilidade não ocorreu com a blenda. As esponjas preparadas com a blenda foram estudadas após neutralização e o MEV mostrou que o uso de EDC/NHS alterou a morfologia levando a formação de poros interconectados. Nos ensaios de absorção em tampão de PBS foi observado que o uso de ácido acético aumenta a absorção para as esponjas sem EDC/NHS, enquanto para as esponjas com EDC/NHS a absorção é maior quando se usa ácido adípico. Todas as esponjas foram não citotóxicas o que torna esses materiais promissores para serem estudados em aplicações na área médica, tais como material de curativo, implantes, liberação controlada de fármacos. / Chitosan is a natural polymer studied in various fields such as environmental, food, pharmaceutical, biomedical and biotechnology. It can be obtained from different polymorphic forms of chitin, of which the form &beta; has proven advantageous because it promotes more homogeneous and chemical modifications leads to a final product less allergenic. Chitosan can be combined with other compounds and thus further improve its properties. The aim of this study was to analyze how the use of adipic acid, replacing acetic acid affects the properties of gels and sponges of chitosan and chitosan/gelatin, which were subsequently crosslinked with EDC/NHS. The techniques used for these studies were: rheology, FTIR, SEM, absorption in PBS and cytotoxicity assays. In rheology, it was observed that increasing the concentration of chitosan was possible to prepare more elastic and viscous gels. The same occurs in the presence of gelatin or EDC/NHSO. The effect of the use of adipic acid to replace the acetic acid was also shown on rheological measurements, because the gels with 2% chitosan or chitosan/gelatin without EDC/NHS were more elastic and more viscous when the adipic acid has been used. The FTIR spectra showed the presence of interactions between chitosan and gelatin and the formation of amide II Bonds after crosslinking with EDC/NHS. In the preparation of the sponges it was observed that the gels of chitosan with adipic acid generated unstable sponges crumbled during neutralization, but this instability does not occur with the blend. Sponges prepared with the blend were studied after neutralization and SEM showed that the use of EDC/NHS altered the morphology leading to the formation of interconnected pores. The use of acetic acid increases the absorption in PBS for sponges without EDC/NHS, while for sponges with EDC/NHS the absorption is greater when adipic acid was used. All sponges were non-cytotoxic making them promising materials to be studied for applications in the medical field, such as dressing materials, implants, controlled drug release.

Bacteria are among the most abundant microorganisms on earth, and can be found in essentially every environment. When a clean surface is exposed to media containing planktonic bacteria, the bacterial cells will attach to the surface and aggregate to form what is known as a biofilm. Biofilms have been shown to negatively affect many industries including medical, industrial, and food science applications. While biofilms have been well characterized from a microbiology perspective, there has been much less research from a materials science standpoint. It is hypothesized that the material properties of the substratum (such as the micro-structure) have a significant impact on biofilm growth. To research this hypothesis, protocol was established in order to produce, analyze, and study biofilms in a static exposure system. Though simple, the static bioreactor was proved to be adequate for inducing microbial attachment to processed samples. Methodologies for analyzing the established biofilms were presented, and an experimental procedure was proposed that enables the correlation of material properties to microbial growth on the substratum. The experimental procedure utilized Design of Experiments in a three factor, two level study that identified the interaction of Material Composition, Surface Conditions, and the Effect of Welding on microbial growth. In a trial iteration of the experiment, samples of 303 and 304 Stainless Steel were mounted in Bakelite and processed. Some samples were sanded to 600 grit sand paper, while others were polished to 1µm. The samples were exposed to biologically active natural water and imaged with scanning electron microscopy. Preliminary results were presented, and limitations of the study were identified.

A complex network of transcription factors, which are regulated by signalling molecules, is responsible in coordinating the formation of differentiated skeletal and cardiac myocytes from undifferentiated stem cells. The present study aims to understand and compare the transcriptional regulation of skeletal and/or cardiac muscle development in the absence of Sox7 or in the presence of a collagen-based matrix in P19 embyonal carcinoma (EC) and mouse embryonic stem (ES) cells. First, knock-down of Sox7 , by shRNA, in muscle inducing conditions (+DMSO) and in the absence of RA (-RA), decreased muscle progenitor transcription factor and myogenic regulatory factor (MRF) levels, suggesting that Sox7 is necessary for myogenesis. However, knock-down of Sox7 in the presence of RA (+RA) and DMSO increased expression of muscle progenitor markers and MRFs, suggesting that Sox7 is inhibitory for myogenesis +RA. Furthermore, Sox7 overexpression enhanced myogenesis -RA, but inhibited myogenesis and enhanced neurogenesis +RA. These results suggest an important interplay between RA signalling and Sox7 function during P19 differentiation. Second, Q-PCR analysis showed that compared to the mouse ES cells differentiated on the regular TC plates, differentiation on the collagen matrices had a higher expression of skeletal and cardiac precursors, MRFs and terminal differentiation markers. Collagen alone enhanced myotube formation. The enhanced collagen matrix, containing the oligosaccharide sialyl LewisX (sLeX), specifically enhanced cardiomyogenesis. These studies have added to our understanding of the transcriptional regulation of premyogenic mesoderm factors and the role of Sox7 in this process. In addition these studies provide a vision for possible use of biomaterials in directed differentiation of stem cells for the purpose of cell therapy.

Treatment of cardiac diseases involves transplantation of donor hearts, since the damaged heart has limited self-regeneration potential. An alternative treatment option has emerged as engineered cardiac tissues, grown in vitro by cultivation of cardiac cells on biomaterials, have comparable properties to native myocardium and can be implanted for cardiac repair. Major current limitations are a viable cell source and adequate vascularization to support cell survival. In this thesis, two proangiogenic biomaterials, a scaffold and a hydrogel, were developed to achieve vascularization in vitro and in vivo for cardiac repair. Scaffold patches are suitable for repairing congestive heart failure or congenital malformations, while injectable biomaterials allow minimally-invasive treatment post-myocardial infarction (MI). In the first aim, a collagen scaffold with covalently immobilized vascular endothelial growth factor (VEGF) was developed, and improved cell mobilization, survival and proliferation when used for free wall repair in adult rats. This increased angiogenesis, which aided in retaining the biomaterial size to allow tissue growth. In the second aim, a collagen-chitosan hydrogel with encapsulated thymosin β4 (Tβ4) was developed to 1) recruit cells from the heart epicardium for repair post-MI in vivo, and 2) guide capillary outgrowths from arteries and veins to form oriented capillary structure for in vitro cardiac tissue engineering. Results showed that the encapsulation of Tβ4 into collagen-chitosan hydrogels led to cell outgrowths from rat or mouse cardiac explants in vitro. A portion of the recruited cells were CD31-positive endothelial cells (ECs) that formed tubes. The hydrogel was injected in vivo to increase vascularization and number of cardiomyocytes within the infarct area post-MI, which improved left ventricular wall thickness. Tβ4-hydrogel also promoted the outgrowth of capillaries from vascular explants that followed the direction of the hydrogel-coated grooves of a micropatterned polydimethylsiloxane (PDMS) substrate. These capillary outgrowths eventually formed a vascular bed for engineering vascularized cardiac tissues. This thesis presents two bioinstructive biomaterials with sustained and localized delivery of angiogenic molecules to be used for in situ cardiac repair based on improved vascularization. The use of cell-free bioactive materials overcomes limitations of cell isolation and expansion as required for cell therapies or implantation of engineered tissues.

An earlier approach to restore homeostatic levels of ECM degrading matrix metalloproteases (MMPs) by the Sefton Lab utilized hydroxamate-based MMP inhibitory (MI) beads. While the MI beads delayed ECM degradation in the context of skin wound healing, they caused elevated cell infiltration in a subcutaneous implant model. The primary goal of this project was to further investigate this finding using an air pouch implant model in mice and a different control group – methacrylic acid-based (MAA) beads. Exudate analysis indicated that the MI beads, implanted subcutaneously with gelatin discs, elicited a similar biological response as the MAA beads. Exudates corresponding to both biomaterials had similar cell counts and chemokine levels, which were greater than those corresponding to the control used earlier, poly-methyl methacrylate-based (PMMA) beads. Further, both MI and MAA beads activated infiltrating macrophages in the classical manner, and influenced the activity of an MMP8 catalytic domain in a similar manner.