O surgimento das matrizes de regeneração dérmica nas duas últimas décadas permitiu um grande avanço no tratamento tanto das queimaduras agudas como das sequelas. No entanto, ainda há carência de informações sobre a relação entre os resultados clínicos e o que ocorre no tecido com cada tipo de matriz. O objetivo deste estudo foi avaliar prospectivamente os aspectos clínicos quanto à qualidade de pele, escala de Vancouver e POSAS, função e retração da área tratada e os aspectos histológicos na microscopia de luz e eletrônica, com o uso de duas matrizes de regeneração dérmica, ambas de colágeno bovino, uma de duas camadas, recoberta com lâmina de silicone e outra sem. Vinte e quatro pacientes, sorteados 12 em cada grupo, tiveram suas retrações cicatriciais secundárias à queimaduras tratadas em duas cirurgias, a primeira de liberação da retração e colocação da matriz e a segunda, colocação do auto enxerto de pele; em ambas as cirurgias foi utilizado o curativo de pressão negativa. As avaliações da escala de Vancouver e medidas da retração da área foram realizadas no pré-operatório, 1, 3, 6 e 12 meses e a escala de POSAS e avaliação funcional no pré-operatório e aos 12 meses. As biópsias foram colhidas no pré-operatório, no dia da colocação do enxerto de pele, 12 dias, 2, 6 e 12 meses após o enxerto. A avaliação clínica mostrou retração de todas as áreas tratadas, melhora da qualidade da pele e funcional em todos os pacientes. A matriz com silicone, mostrou superioridade dos resultados quanto a qualidade da pele, função e menor retração da área tratada. A análise histológica mostrou o crescimento de tecido conjuntivo denso idêntico ao tecido cicatricial original, sem diferenças entre as matrizes e que não se assemelha à derme normal. Também não foi observada diferença no diâmetro das fibrilas de colágeno do tecido neoformado, a pele normal e a cicatriz / The advent of dermal regenerate templates has fostered major advances in the treatment of acute burns and their sequelae, in the last two decades. Both data on morphological aspects of the newly-formed tissue, and clinical trials comparing different templates, are still lacking. The goal of this study was to prospectively analyze the outcome of patients treated with two of the existing templates, followed by thin skin autograft. They are both made of bovine collagen, one includes a superficial silicone layer. Surgery was performed on patients with impaired mobility resulting from burn sequelae (n = 12 per template). Negative pressure therapy was applied post-surgically; patients were monitored for 12 months. Data on scar skin quality (Vancouver and POSAS evaluation scales), rate of joint mobility recovery, and graft contraction were recorded; as well as morphological analyses at light microscopical and ultrastructural levels. Improvement in mobility and skin quality were demonstrated along with graft contraction, in all patients. The silicone-coupled template showed the best performance in all aspects. There was sub epidermal growth of dense connective tissue, indistinguishable from the original scars in both templates. The formation of tissue resembling normal dermis was not detected in any of the cases. Likewise, the ultrastructural analysis showed the same architecture of the connective tissue among the template scars and the original scar. No difference was detected when the collagen fibril diameters of the normal skin and of the scars (original and of the two templates) were compared

Introdução: O uso de matrizes dérmicas é uma opção no tratamento de vários tipos de sequelas de queimaduras. O objetivo deste estudo foi avaliar e comparar a contração tardia dos enxertos de pele de espessura parcial autólogos utilizados para o tratamento de sequelas de queimaduras associado com as matrizes dérmicas Integra®, Matriderm® e Pelnac®. Métodos: Este é um ensaio clínico prospectivo, randomizado e controlado, e foi aprovado pelo Comitê de Ética em Pesquisa da instituição. O estudo comparou a contração da área do enxerto de pele de espessura parcial autólogo associado ou não com a matriz dérmica após 1, 3, 6 e 12 meses da cirurgia para tratamento de sequelas de queimaduras em pacientes da Unidade de Queimados de um hospital universitário. Os critérios de inclusão foram pacientes acima de 18 anos de idade, com uma ou mais sequelas de queimadura causando prejuízo funcional, com seguimento pós-queimadura de no mínimo 1 ano, e com indicação de tratamento cirúrgico usando enxerto de pele de espessura parcial. Os critérios de exclusão foram a perda do seguimento clínico, perda da matriz dérmica e falha na integração de mais de 10% do enxerto de pele parcial. As sequelas dos pacientes foram submetidas a randomização permutada em bloco por sorteio (de acordo com as normas do CONSORT) para um de quatro grupos: Grupo Integra® (n=10), Grupo Pelnac® (n=10), Grupo Matriderm® (n=9), e Grupo Controle (n=10), cujo tratamento envolveu apenas o enxerto de pele sem uso de matriz dérmica. Utilizamos este tipo de randomização para garantir um número balanceado de participantes nos diferentes grupos. As cirurgias foram realizadas pelo mesmo cirurgião e consistiu na ressecção da sequela da queimadura, gerando um defeito de cobertura cutânea. As cirurgias foram em dois tempos para os grupos Integra® e Pelnac® (primeiro a ressecção da sequela e colocação da matriz dérmica, e 21 dias depois remoção da lâmina de silicone e aplicação do enxerto de pele de espessura parcial autólogo sobre a matriz), ou em tempo único para os grupos Matriderm® e Controle (ressecção da sequela, colocação da matriz e do enxerto de pele de espessura parcial, ou apenas do enxerto de pele de espessura parcial). A obtenção dos enxertos de pele foi realizada por meio de dermátomo elétrico com regulagem de 0,2mm de espessura em todos os grupos. No intraoperatório, o contorno do defeito tridimensional (que corresponde ao contorno da matriz ou do enxerto de pele) foi marcado com azul de metileno e transferido para um anteparo maleável estéril de superfície plana, sempre em posição de extensão máxima para membros e pescoço. A obtenção das medidas no pós-operatório foi realizada da mesma forma com 1, 3, 6 e 12 meses. Essas medidas foram posteriormente transferidas para uma folha de papel com escala de centímetros, e submetidas a fotografias com máquina fotográfica com plano focal paralelo ao da folha de papel e com distância fixa de 40 cm. O cálculo das dimensões foi realizado por meio do software de planimetria digital \"Image J\" e comparados entre os grupos. Dessa forma, foi possível calcular a porcentagem de contração do enxerto de pele de espessura parcial em relação ao defeito original. A análise estatística foi realizada pelo software SAS® 9.2 utilizando o modelo de regressão linear com efeitos mistos (efeitos aleatórios e fixos), e o nível designificância adotado foi 5%. Resultados: Foram operadas 39 sequelas de queimaduras em 30 pacientes, sendo 19 do sexo masculino e 21 do sexo feminino. Após 12 meses, os resultados mostraram que o Grupo Controle apresentou menores taxas de contração do enxerto comparado aos grupos das matrizes dérmicas Integra® (p<0,01), Matriderm® (p=0,01), e Pelnac® (p<0,01); o Grupo Pelnac® mostrou uma contração do enxerto de pele estatisticamente maior comparado ao Grupo Matriderm® (p<0,01) e ao Grupo Integra® (p=0,02); a contração do enxerto de pele do Grupo Integra® não apresentou diferença significativa comparado ao Grupo Matriderm® (p=0,16). A contração variou bastante entre as diversas áreas do corpo, e a região cervical apresentou uma elevada taxa de contração em todos os grupos, sendo estatisticamente maior comparado com as outras regiões do corpo (p<0,01). Conclusão: No tratamento de sequelas de queimaduras, a contração tardia dos enxertos de pele de espessura parcial foi maior quando associados com matrizes dérmicas, em comparação ao enxerto de pele sem uso de matriz. A contração dos enxertos teve grande variabilidade de acordo com o local da sequela, sendo que a região cervical apresentou os maiores índices de contração. / Purpose: The use of dermal matrices is an option in the treatment of burn sequelae. The objective of this study was to evaluate and compare the contraction of autologous split-thickness skin grafts used for the treatment of burn sequelae associated with dermal matrices. Methods: This is a prospective, randomized, controlled clinical trial, comparing the contraction of the autologous split-thickness skin graft associated or not with dermal matrix after 1, 3, 6 and 12 months postoperatively for the treatment of burn sequelae. Patients were selected from the Burns Unit of an university hospital, and our Institutional Review Board approved this study. Inclusion criteria were patients with one or more burn sequelae causing functional impairment, with post-burn follow-up of at least one year, and with an indication of surgical treatment using split-thickness skin graft. Exclusion criteria were the loss of follow-up, loss of the dermal matrix, and failure to integrate more than 10% of the split-thickness skin graft. Patients\' sequelae were randomly assigned to a randomized block design (according to the CONSORT standards) for one of four groups: Integra® Group (n = 10), Pelnac® Group (n = 10), Matriderm® Group (n = 9), and Control Group (n = 10), whose treatment involved only the skin graft without dermal matrix. Surgeries were performed by the same surgeon and consisted of resection of the burn sequelae, leading to a tegument defect. Surgeries were performed in two stages for the Integra® and Pelnac® groups (first resection of the sequela and placement of the dermal matrix, and 21 days later removal of the silicon sheet and application of the skin graft on the matrix), or in single stage for the Matriderm® and Control groups (resection of the sequelae, placement of the matrix and skin graft, or only the skin graft). The skin grafts were obtained using an electric dermatome with the regulation of 0.2 mm thickness in all groups. During the surgery, the contour of the three-dimensional defect (corresponding to the contour of the matrix or the skin graft) was marked with methylene blue and transferred to a sterile, flat surface, always in the position of maximum extension for limbs and neck. This procedure was also performed after 1, 3, 6 and 12 months postoperatively. Then, it was transferred to a sheet of paper with a centimeters scale and submitted to pictures using a camera with a fixed distance of 40 cm. The measures of the dimensions were carried out using the digital planimetry software \"Image J\" and compared among the four groups. Thus, we calculate the percentage of contraction of the split-thickness skin graft comparing it to the original defect. Statistical analysis was carried out using the linear regression model with mixed effects (random and fixed effects), and the significance level adopted was 5%. Results: Thirty-nine burn sequels were performed in 30 patients, 19 male and 21 female. Twelve months postoperatively, the results showed that the Control Group presented lower rates of skin graft contraction compared to the Integra® (p < 0.01), Matriderm® (p = 0.01) and Pelnac® (p < 0.01); the Pelnac Group showed a statistically larger contraction of the skin graft compared to the Matriderm® Group (p < 0.01) and the Integra® Group (p = 0.02); the contraction of the skin grafts from the Integra® Group did not present a significant difference compared to the Matriderm® Group (p = 0.16). The contraction varied widely among the treated areas, and the cervical region showed a high rate of contraction in allgroups, being statistically higher compared to the other body regions (p < 0.01). Conclusion: In the treatment of burn sequelae, the late contraction of split-thickness skin grafts was greater when associated with dermal matrices, in comparison to the skin graft without dermal matrix. The contraction of the skin grafts had great variability according to the location of the sequelae, and the cervical region had the highest rates of contraction.

Fibroblastos gengivais desempenham um importante papel na regeneração de tecidos moles de proteção do periodonto. Alloderm® (MDA) é um substituto alógeno muito utilizado e estudado em periodontia. O objetivo do presente estudo foi avaliar, in vitro, se a MDA é uma matriz tridimensional adequada, através de sua resposta à cultura de fibroblastos gengivais e células neoplásicas; e, ainda, se os subprodutos da MDA influenciam o comportamento celular. Material e Métodos: Fibroblastos gengivais de cão (FGC) e fibroblastos gengivais humanos (FGH) foram obtidos pela técnica do explante a partir de tecido conjuntivo gengival de, respectivamente, três indivíduos e três cães saudáveis. As células FGC, FGH e B16F10 de melanoma murino foram cultivadas sobre a MDA por até 14 dias. Os seguintes parâmetros foram avaliados: presença, morfologia e distribuição de FGC, FGH e B16F10 por fluorescência direta; viabilidade de FGC e FGH por MTT; e o efeito do meio de cultura condicionado (MC) em MDA por 24 h na viabilidade celular de FGC por MTT. Os dados quantitativos foram submetidos aos testes estatísticos Mann-Whitney e Kruskal-Wallis, seguido pelo método de Dunn para comparações múltiplas (nível de significância: 5%). Resultados: A epifluorescência revelou que, em 12 h, FGH e FGC estavam aderidos à superfície da MDA em baixa densidade celular, exibindo morfologia poligonal com núcleos esféricos, enquanto que, aos 7 e 14 dias, essas células apresentavam com formato alongado, núcleos ovalados e citoesqueleto de actina com fibras de estresse. Aos 7 e 14 dias, FGC apresentavam-se distribuídos de forma desigual sobre a MDA, formando uma camada celular descontínua, sem aumento no número de células entre os períodos; FGH formaram uma monocamada celular na superfície da MDA, estando presentes em maior número após 14 dias de cultivo (p<0,05); e B16F10 exibiram um aumento no número de células de 12 h para 7 dias (p<0,05), apresentando-se dispostas em aglomerados celulares, principalmente na superfície da MDA, com a formação de camada contínua aos 14 dias. Notou-se maior número de células nas amostras cultivadas com B16F10, seguido por FGH e FGC aos 7 dias (p<0,05). Aos 14 dias, FGH e B16F10 estavam presentes em maior número, com diferença estatística significante em relação aos FGC (p<0,05). Foi observada maior porcentagem de células na superfície (p<0,05) do que no interior da MDA e essa proporção manteve-se estável durante os períodos avaliados para todos os tipos celulares. O ensaio de MTT indicou maior viabilidade celular nas amostras cultivadas com FGH comparado a FGC (p=0,024), aos 7 e 14 dias. Notou-se um decréscimo na viabilidade celular em culturas cultivadas em MC, com diferença estatística entre os grupos em 48 e 72 horas (p<0,05). Conclusão: Podemos concluir que fibroblastos gengivais e mesmo células altamente proliferativas, como B16F10, povoam apenas superficialmente a MDA e que FGC são afetados negativamente pelos subprodutos da MDA, reduzindo sua viabilidade. / Gingival fibroblasts play a central role in oral soft tissue regeneration. Alloderm® (Alloderm® - ADM) is the most used and studied allogeneic substitute. The aim of this investigation was to verify if ADM is a suitable threedimensional matrix, through its in vitro response to gingival fibroblasts and cancerous cells lineage and, also, if ADM end products affect cellular behavior. Methods: Canine gingival fibroblasts (CGF) and human gingival fibroblasts (HGF) cultures were established by the explant technique of gingival connective tissues of three dogs and three healthy patients, respectively. CGF, HGF and B16F10 cells of murine melanoma were seeded on ADM and grown for up to 14 days. The following parameters were assessed: presence, morphology and distribution of CGF, HGF e B16F10 by direct fluorescence; CGF and HGF viability by MTT; and the effect of culture medium conditioned (CM) in the MDA for 24 h on CGF viability by MTT. Quantitative data were submitted to Mann-Whitney and Kruskal-Wallis tests, followed by Dunn\'s method. Results: Epifluorescence revealed that CGF and HGF were adherent and exhibited a polygonal morphology at 12 h while at 7 and 14 days they were spread, exhibiting an elongated shape and the actin cytoskeleton assembled into stress fibers. CGF were unevenly distributed on ADM surface, showing no increase in cell number over the experimental periods; HGF formed a monolayer on the ADM surface, in a higher number at 14 days (p<0,05); B16F10 exhibited na increase in cell number in 7 days (p<0,05), and were mainly arranged in cell aggregates on the ADM, forming a continuous layer at 14 days. A higher percentage of cells on the ADM surface (p <0.05) compared to inside the matrix was observed for all cell types in all periods. MTT values indicated higher cell viability in samples cultured with HGF compared to CGF (p=0.024). A significantly lower cell viability for CGF grown in CM compared to cells grown in non conditioned medium at 48 and 72 h (p <0.05) was noticed. Conclusion: Gingival fibroblasts and even highly proliferative cells as B16F10 can be only superficially located on ADM and CGF are negatively affected by ADM end products, reducing its viability.

Objectives: Tooth replacement therapy using endosseous implants has become an essential component of contemporary dental practice. While a plethora of factors determine clinical success, the bucco-lingual and apico-coronal dimensions of the peri-implant mucosa play an important role in both esthetics and the maintenance of peri-implant health. Studies, most of which treat mucogingival defects in the natural dentition, comparing acellular dermal matrix (ADM) and autologous subepithelial connective tissue grafts (sCTG) have shown similar clinical outcomes. The purpose of this non-inferiority trial is to determine the clinical efficacy of ADM in the augmentation of peri-implant mucosa thickness (PMT) as compared to an autologous sCTG in human adults. Methods: Twenty healthy adults treatment planned for a single tooth implant restoration in need of simultaneous peri-implant mucosa augmentation at the time of implant placement were recruited on the basis of an eligibility criteria. Patients were randomly assigned to the control group (autologous sCTG), or the experimental group (ADM allograft). Clinical measurements of mucosal thickness at the site were made with a periodontal probe and an endodontic spreader at baseline and 16 weeks post-op. These measurements were made by a masked, calibrated examiner. Gingival health, oral hygiene, wound healing and patient reported outcomes were also obtained. Mann-Whitney U tests were used to compare the mean mucosal thickness changes between the groups. Results: The mean gain in PMT was approximately 1.5mm in the control group and 0.8mm in the experimental group. When measured at 1, 3 and 5mm apical from the CEJ, only the 3mm site exhibited a difference between the groups that approached statistical significance (control: 2.08 ± 0.80mm, test: 0.83 ± 1.37mm, Mann Whitney U = 10.00, p=0.05). Changes in keratinized mucosa width, healing index and patient reported outcomes were generally similar between the two groups. Conclusions: Within the limitations of this study, both autologous sCTG and ADM appear to be adequate materials to augment PMT without sacrificing other relevant clinical parameters and/or patient related outcomes.

The Center for Disease Control and Prevention (CDC) reports indicate that 8% and 6.3% of Kentuckians consume enough fruits and vegetables, respectively. The Plate It Up! Kentucky Proud (PIUKP) project is a recipe-development project that aims to boost produce consumption by incorporating local fruits and vegetables. The purpose of this study was to implement promotional strategies using PIUKP recipes at farmers’ markets and determine their effects on consumers’ intent of purchasing and preparing the produce. The study was conducted at nine farmers’ markets across Kentucky (n=300) in collaboration with Cooperative Extension agents/assistants. The consumers’ impression of the sample was positively associated with their intent to purchase fruits and vegetables the same day (t = 0.36; p < 0.0001), in future (t=0.43; p < 0.0001), and prepare the respective recipes (t=0.51; p < 0.0001). Distribution of recipe cards was also positively correlated with consumers’ intent to prepare recipes (t=0.35; p < 0.0001). However, no significant association was found between the self-reported fruit and vegetable intake and their respective dermal carotenoid score. Findings from this study support the use of promotional strategies as a means to influence produce intake among farmers market consumers. Future studies can apply these strategies and explore the extent of effect they have on dietary intake.

The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered to the wound site through construct pre-seeding. Lastly, in vivostudies were conducted to evaluate the construct as an applied biomaterial and as a cellular delivery device. Wound closure and quality were assessed, and neo-vascularization quantified. This project will provide insight into the tissue engineering field regarding cell-based therapies and dermal wound healing.

Embryonic stem cells (ESCs) can differentiate into all somatic cells, and as such, are a promising cell source for therapeutic applications. In vitro, ESCs spontaneously differentiate via the aggregation of cells into embryoid bodies (EBs), which recapitulate aspects of early embryogenesis and harbor a unique reservoir of cues critical for tissue formation and morphogenesis. Embryonic healing responses employ similar intrinsic machinery used for tissue development, and these morphogenic cues may be captured within the EB microenvironment. Recent studies have shown that when injected into injury or defect models in vivo, ESCs synthesize and secrete extracellular factors that ultimately contribute to repair, suggesting that these molecules may be as important for regenerative therapies as functional differentiation of the cells. The overall objective of this project was to develop novel acellular matrices derived from differentiating ESCs undergoing morphogenesis. The central hypothesis was that embryonic matrices contain complex mixtures of extracellular factors that, when isolated, retain bioactivity and enhance wound healing in an adult environment. The overall objective was accomplished by: (1) investigating the production of extracellular matrix (ECM) by differentiating ESCs as a function of differentiation time; (2) assessing the ability of solvents to efficiently decellularize EBs; and (3) evaluating the healing response elicited by acellular matrices derived from EBs in a murine dermal wound healing model. Endogenous ECM synthesis by EBs varied with time and was associated with specific differentiation events. Novel techniques were developed to effectively remove cell components from EBs in order to extract complex, bioactive acellular matrices. EB-derived acellular matrices significantly enhanced the healing of excisional dermal wounds in mice, indicating the potency of extracellular factors synthesized by ESCs. All together, these studies demonstrate that acellular matrices derived from ESCs retain morphogenic factors capable of influencing tissue repair. In addition, this work lays the foundation for future studies to further examine the functional role of endogenous matrix molecules on ESC differentiation and to evaluate the utility of a stem cell-derived matrix for a variety of regenerative medicine applications.

Hair disorders cause significant distress. The main, but limited, treatment for hair loss is minoxidil, an ATP-sensitive potassium (KATP) channel opener whose mechanism of stimulation is unclear. The regulatory component of KATP channels has three forms: SUR1, SUR2A and SUR2B which all respond to different molecules. Minoxidil only opens SUR2B channels, though SUR1 and SUR2B are present in human hair follicles. To expand our understanding, the red deer hair follicle model was used initially. Deer follicles expressed the same KATP channel genes as human follicles when growing (anagen), but no channels were detected in resting follicles. This reinforces the importance of KATP channels in active hair growth and the usefulness of the deer model. To assess whether SUR1 KATP channels are actually involved in human hair growth, the effects of a selective SUR1 channel opener, NNC55-9216, on scalp follicle growth in organ culture was examined. NNC55-9216 stimulated anagen; its effect was augmented by minoxidil. This creates the potential for more effective pharmaceuticals to treat hair loss via SUR1 channels, either alone or in combination with minoxidil. The dermal papilla plays a crucial regulatory role in hair follicle activity determining the type of hair produced. Minoxidil had no effect on dermal papilla cell proliferation, but altered the profile of proteins produced when assessed by proteomics. Further research into the roles of KATP channels and greater understanding of the significance of these protein changes should enhance our knowledge of hair biology and help the development of new, improved therapies for hair pathologies.

Aims and objectives: The research aims and objectives of this thesis were: (i) to review literature pertaining to different dermal exposure assessment methods; (ii) to assess dermal exposure of refinery workers to nickel and/or cobalt by making use of skin wipes as a removal method; (iii) to assess concurrently the skin condition of the above mentioned workers by measuring skin hydration, transepidermal water loss (TEWL) and skin surface pH, and (iv) to compare South African skin notations and sensitisation notations with those of other developed countries. Methods: Refinery workers from two base metal refineries participated in this study. Skin condition and dermal exposure was measured on different anatomical areas before, during and at the end of a work shift. Dermal exposure to nickel and/or cobalt was assessed with Ghostwipes TM as a removal method. Wipe samples of potentially contaminated surfaces in the workplace were also collected. Wipes were analysed for nickel and/or cobalt according to NIOSH method 9102, using Inductively Coupled Plasma-Atomic Emission Spectrometry. The assignment and use of skin notations and sensitisation notations in South African legislation and six other developed countries were compared. Results: To date, occupational dermal exposure has been reported for numerous substances by making use of surrogate skin methods (interception methods), removal methods and fluorescent tracer methods (in situ detection methods). From published literature it is evident that skin (dermal) wipes, as a removal method, are the most appropriate method to assess dermal exposure to metals. Varying degrees of skin dryness (low hydration indices) and impaired barrier function (high TEWL indices) are reported, with the hands being implicated the most. However, normal skin condition is also reported for some anatomical areas. Skin surface pH for all anatomical areas sampled decreased significantly during the shift, but remained in normal range. Dermal exposure to nickel occurred during the shift at the electro-winning plant of one refinery, while dermal co-exposure to cobalt and nickel occurred at the cobalt plant of the other refinery. At both of the refineries, cobalt and/or nickel was collected from the workers’ skin even before the shift. Also, dermal exposure to these metals was highly variable between individual workers. Skin notations in South African legislation had a mean agreement of between 42.9% and 45.8% with other countries, while agreement for sensitisation notations was only 3.6% between countries. / Thesis (Ph.D. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Acne is a multifactorial skin disease affecting about 80 % of people aged 11 to 30. Several systemic and topical treatments are used to treat existing lesions, prevent scarring and suppress the development of new lesions. Topical therapy is often used as first line treatment for acne, due to the location of the target organ, the pilosebaceous unit, in the skin. Retinoids are widely used as oral or topical treatment for this disease, with tretinoin and adapalene being two of the most used topical retinoids. The transdermal route offers several challenges to drug delivery, e.g. the excellent resistance of the stratum corneum to diffusion, as well as variable skin properties such as site, age, race and disease. Some additional difficulties are associated with the dermatological delivery of tretinoin and adapalene, which include suboptimal water solubility of the retinoids, isomerisation of tretinoin in the skin, mild to severe skin irritation, as well as oxidation and photo–isomerisation of tretinoin, even before crossing the stratum corneum. Researchers constantly strive to improve dermatological retinoid formulations in order to combat low dermal flux, skin irritation and instability. The release kinetics of tretinoin varies greatly according to the way in which it is incorporated into the formulation and according to the type of formulation used. Little research has been conducted regarding improved formulations for adapalene. Pheroid technology is a patented delivery system employed in this study in order to improve the dermal delivery of retinoids. Tretinoin and adapalene were separately incorporated into castor oil, vitamin F and Pheroid creams. The creams were evaluated in terms of their in vitro retinoid release, in vitro transdermal diffusion and stability. Castor oil and Pheroid creams were superior in terms of release and dermal delivery of adapalene. Tretinoin was best released and delivered to the dermis by castor oil cream. The castor oil creams were the most stable formulations, whereas the Pheroid creams were the most unstable. In terms of release, dermal diffusion and stability, castor oil cream proved to be the most suitable cream for both tretinoin and adapalene. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.