Electrospinning for skin tissue engineering and drug-eluting antimicrobial biomaterials

A critical challenge in the design of biomaterials for tissue engineering relies on the development of tissue-specific biomimetic scaffolds capable of replacing cell-matrix interactions required for the repair of injured tissues. Further, such biomaterials with the additional capacity to prevent bacteria contamination can resolve issues surrounding surgical prosthesis infection. Fibrous micro- and nanostructures are extensively researched in tissue engineering due to their intrinsic similarities to decellularised human tissues. Among the several fibre-forming processes, electrospinning has drawn much attention due to its ability to produce scaffolds that morphologically resemble the native extracellular matrix (ECM) of human tissues. Electrospinning is a versatile method that uses electrohydrodynamic principles to produce fibres with diameters ranging from microns to tens of nanometres. By varying the chemistry and morphology of the fibres, it is feasible to attain different physiological and mechanical responses. The wide array of raw natural and synthetic materials – including polymers and complex molecules – that can be used to electrospin fibres can resolve well-documented problems associated with the inferiority of synthetic biomaterials and the limitations of biological tissues. In this thesis, electrospinning is utilised to contribute to the engineering of advanced ECM-mimicking biomaterials. The work will focus on (1) improving the physicochemical and mechanical responses of skin substitutes and (2) preventing mesh-associated surgical site infection. The initial study of this thesis presents the design and construction of a nozzle-free electrospinning device, which is an economically viable method of scaling-up fibre production output. The equipment is then used to fabricate elastic skin-like composite nanofibres consisting of poly(vinylpyrrolidone) (PVP) and poly(glycerol sebacate) (PGS). The findings indicate that the mechanical properties of the electrospun mats could be tuned by varying the concentration of PGS and the molecular weight of PVP within the blends. Photocrosslinking the fibres prevented the rapid degradation of the composite mats due to the hydrophilic nature of PVP, making it feasible to assess the biological responses of the construct in vitro, displaying good viability and proliferation of human dermal fibroblasts. This study provides a different approach towards the development of skin substitutes, based on the fact that mechanical stimuli influence the ability of dermal cells to adapt and reconstruct the ECM at an injured site; being able to adjust the mechanics to those of different anatomical sites of the body can have a positive effect on the overall outcome of a healing wound. Synthetic biomaterials tend to present suboptimal cell growth and proliferation, with many studies linking this phenomenon to the hydrophobicity of such surfaces. This thesis continues with the development of a protocol for silk fibroin extraction from Bombyx mori cocoons, which achieved significantly increased yields of the protein in a third of the time required by the conventional molecular cut-off extraction approach. The extracted silk fibroin was then used to produce electrospun membranes consisting of poly(caprolactone) (PCL) blended with variant forms of PGS. The main aim of this work was the development of fibre mats with tuneable hydrophobicity/hydrophilicity properties, depending on the esterification degree and concentration of PGS within each composite. By altering the surface properties of the electrospun membranes, the trinary composite biomaterial presented improved fibroblast attachment behaviour and optimal growth in comparison to PCL-only fibrous mats. The study continued with the development of an ultralight-weight nanostructured bicomponent antimicrobial construct with a similar microstructure to biologic meshes, which preserved the required mechanical integrity of synthetic mesh materials. A core/shell nanofibrous structure was developed, consisting of nylon-6 in the core and chitosan/polyethylene oxide in the shell. The bicomponent fibre structure comprised a binary antimicrobial system incorporating 5-chloro-8-quinolinol in the chitosan-shell, with the sustained release of polyhexamethylene biguanide from the nylon-6 core of the fibres. The antimicrobial nanofibres were found to elicit a robust bactericidal response, in vitro, against the two most commonly occurring pathogenic bacteria in deep incisional surgical site infections; Staphylococcus aureus and Pseudomonas aeruginosa. The results of this study advocate that the bicomponent nanofibres developed can be a promising alternative to biologic meshes, employed for hernia repair today, due to similar architecture and mechanics, but at the same time capable of actively protecting the patient from subsequent mesh-associated infections, thus tackling this life-threatening postoperative complication. Overall, the work in this thesis has expanded upon the fields of skin tissue engineering and drug-eluting antimicrobial biomaterials, potentially guiding new areas of research

Mechanics of Biomaterials

The mechanical behavior of biomedical materials and biological tissues are important for their proper function. This holds true, not only for biomaterials and tissues whose main function is structural such as skeletal tissues and their synthetic substitutes, but also for other tissues and biomaterials. Moreover, there is an intimate relationship between mechanics and biology at different spatial and temporal scales. It is therefore important to study the mechanical behavior of both synthetic and livingbiomaterials. This Special Issue aims to serve as a forum for communicating the latest findings and trends in the study of the mechanical behavior of biomedical materials

Development and Fabrication of Novel Woven Meshes as Bone Graft Substitutes for Critical Sized Defects

With more than $2.5 billion spent per year, and over 2.2 million procedures conducted annually worldwide, bone grafting continues to be a large part of the treatment strategy for large non-healing bone defects (critical-sized defects). However, complication rates (\u3e20%), donor shortage, and donor site morbidity have led to the promotion of bone tissue engineering as an important option in these cases. This work explored the use of a novel bio-loom to make woven polymeric meshes as viable bone tissue engineering scaffolds. Melt-spun poly-l-lactide and poly-l-lactide-co-ε-caprolactone fibers were used to produce mesh with varying porosity, pore size, and cellular affinity. Fluid flow properties and cellular behaviors were characterized in a series of in vitro tests. Mesh with variable properties were effectively created and the modulation of mesh specifications resulted in significant differences in cell metabolic activity and deoxyribonucleic acid concentrations. Changes in mesh parameters also significantly effected mesh permeability. Additionally, an interactive camp was designed to investigate ways to encourage underrepresented minority middle school students to pursue Science, Technology, Engineering, and Mathematics (STEM) careers was conducted. Results showed that parental encouragement, the external STEM environment, and extracurricular STEM exposure were closely related to a student\u27s likelihood to express interest in a STEM career. Student interest in STEM careers significantly increased after participation in an interactive camp based on mesh-based modules. Further work explored the effect of early research experiences on the development of research identity for underrepresented minority science and engineering undergraduates. Results showed that students participating in this program significantly increased their research identity through increased self-recognition and competence in research activities

XXII International Conference on Mechanics in Medicine and Biology - Abstracts Book

This book contain the abstracts presented the XXII ICMMB, held in Bologna in September 2022. The abstracts are divided following the sessions scheduled during the conference

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Major Abdominal Surgical Complications : Innovative Approaches

In this thesis the focus was on three major complications after abdominal surgery: incisional hernia (IH), prolonged postoperative ileus (PPOI), and colorectal anastomotic leakage (CAL). The results were summarized in three parts: _Part 1_ focused on prediction and detection of these surgical complications; _Part 2_ describes different methods to prevent complications; _Part 3_ analyzed also prevention of major surgical complications with a focus on patients at risk. Even anno 2017 it is still necessary to explore new strategies to prevent complications in abdominal surgery. Also with new surgical techniques, for example the use of staplers for colorectal anastomosis, prevention of CAL is still an issue. In addition, early detection of a complication is necessary to prevent from worse. This also requires more attention and research since detection of leakage is still mainly based on clinical observation and the experience of the surgeon. Research on more advanced technical and/ or digital solutions to objectively assess and quantify leakage and other complications is strongly needed. Therefore in this thesis the focus was to develop different strategies that may facilitate prevention, prediction, and diagnosis of different important abdominal surgical complications such as colorectal anastomotic leakage, postoperative ileus, incisional hernia, and infectious complications

Stem cell based therapy retards the progression of osteoarthritis and promotes repair of meniscus injury of sheep model knee joint

ABSTRACT The aim of this study to determine if intra-articular injection of autologous bone marrow mesenchymal stem cells (ABMSCs) could repair surgically induced osteoarthritis in sheep model. Eighteen male healthy sheep (weighed 18-20kg) were divided into two test groups and one control group. The control groups were not different from the test groups with respect to age and weight, but the test animals underwent a bone marrow aspira- tion for cell preparation in the same time of osteoarthritis induction. ABMSCs were isolated from sheep bone marrow and divided into two groups, namely test group A; ABMSCs cultured in FD medium supplemented with 10% fetal bovine serum (FBS), Test group B; ABMSCs were cultured in FD medium supplimented with 1% FBS and 10 ng/ml TGFβ-3 for three weeks. OA was induced by complete excision of the medial meniscus and resection of the anterior cruciate ligament (ACL). Sheep were subjected to exercise for three weeks post OA induction. After 6 weeks post-operation, test groups received direct intra-articular injection of a single dose 10x106 cells suspended in basal medium into injured sheep knee joint. Con- trol animals received basal medium alone. Six weeks post- cel injection, the femoral condyle and the tibial plateau from test and control groups were removed,fixed,photographed, and assessed by two blinded evaluators based on ICRS grading system, decalcified. Specimens were sectioned into 5 µm and stained with H & E and Safranin O. The result demonstrated that Gross observation of femoral condyle and tibia plaetue of the operated knee joint had OA. The severe OA was clearly observed in in control group knee joints. Test group received intra-articular injection of ABMSCs alone showed moderate OA. Interestingly test group B that received intra-articularinjection of TGF-β3 induced ABMSCs showed mild OA. The histological examination showed clear evidence of articular cartilage and menicscus regeneration in test group B of sheep injured knee joint that received TGF-β3 induced ABMSCs when compared with other groups