Patrycja Domalik-Pyzik

Gentamicin release from biodegradable poly-l-lactide based composites for novel intramedullary nails

One of the major problems in orthopedic surgery is infection associated with implantation. The treatment is a very difficult and long-term process. A solution to this issue can be the use of implants which additionally constitute an antibiotic carrier preventing the development of an infection. Prototypes of biodegradable intramedullary nails made of three different composites with a poly(L-lactide) matrix were designed. The nails served as gentamicin sulfate (GS) carrier - an antibiotic commonly used in the treatment of osteomyelitis. The matrix was reinforced with carbon fibers (CF), alginate fibers (Alg) and magnesium alloy wires (Mg), as well as modified with bioactive particles of tricalcium phosphate (TCP) in various systems. In this way, novel, multi-phase and multifunctional degradable intramedullary nails were obtained. The tests demonstrated strong dependence between the type of the modifying phase introduced into the composite, and the rate of drug release. Introduction of gentamicin into the nail structure strengthened and prolonged antibacterial activity of the nails.

Influence of the intramedullary nail preparation method on nail's mechanical properties and degradation rate

When it comes to the treatment of long bone fractures, scientists are still investigating new materials for intramedullary nails and different manufacturing methods. Some of the most promising materials used in the field are resorbable polymers and their composites, especially since there is a wide range of potential manufacturing and processing methods. The aim of this work was to select the best manufacturing method and technological parameters to obtain multiphase, and multifunctional, biodegradable intramedullary nails. All composites were based on a poly(l-lactide) matrix. Either magnesium alloy wires or carbon and alginate fibres were introduced in order to reinforce the nails. The polylactide matrix was also modified with tricalcium phosphate and gentamicin sulfate. The composite nails were manufactured using three different methods: forming from solution, injection moulding and hot pressing. The effect of each method of manufacturing on mechanical properties and degradation rate of the nails was evaluated. The study showed that injection moulding provides higher uniformity and homogeneity of the particle-modified polylactide matrix, whereas hot pressing favours applying higher volume fractions of fibres and their better impregnation with the polymer matrix. Thus, it was concluded that the fabrication method should be individually selected dependently on the nails desired phase composition.

Polylactide- and polycaprolactone-based substrates enhance angiogenic potential of human umbilical cord-derived mesenchymal stem cells in vitro - implications for cardiovascular repair

Recent approaches in tissue regeneration focus on combining innovative achievements of stem cell biology and biomaterial sciences to develop novel therapeutic strategies for patients. Growing recent evidence indicates that mesenchymal stem cells harvested from human umbilical cord Whartons jelly (hUC-MSCs) are a new valuable source of cells for autologous as well as allogeneic therapies in humans. hUC-MSCs are multipotent, highly proliferating cells with prominent immunoregulatory activity. In this study, we evaluated the impact of widely used FDA approved poly(α-esters) including polylactide (PLA) and polycaprolactone (PCL) on selected biological properties of hUC-MSCs in vitro. We found that both polymers can be used as non-toxic substrates for ex vivo propagation of hUC-MSCs as shown by no major impact on cell proliferation or viability. Moreover, PCL significantly enhanced the migratory capacity of hUC-MSCs. Importantly, genetic analysis indicated that both polymers promoted the angiogenic differentiation potential of hUC-MSCs with no additional chemical stimulation. These results indicate that PLA and PCL enhance selected biological properties of hUC-MSCs essential for their regenerative capacity including migratory and proangiogenic potential, which are required for effective vascular repair in vivo. Thus, PLA and PCL-based scaffolds combined with hUC-MSCs may be potentially employed as future novel grafts in tissue regeneration such as blood vessel reconstruction.

Polylactide/polycaprolactone asymmetric membranes for guided bone regeneration

Abstract The aim of this work was to develop bioresorbable, asymmetric membranes for guided bone regeneration (GBR). Two resorbable polymers – polylactide (PLA) and polycaprolactone (PCL) were used in fabrication process. Two different manufacturing methods were applied: electrospinning in the case of PLA and freeze-drying of PCL. Mechanical properties, stability in a water environment and biocompatibility of fabricated membranes were evaluated. Microstructure [scanning electron microscopy (SEM)] of the membranes was assessed in terms of level of porosity, as well as size and shape of the pores. Study showed that combination of electrospinning and freeze-drying methods allows biocompatible PLA/PCL bi-phasic materials of appropriate mechanical properties and diverse microstructure to be produced, that should on the one hand prevent soft tissue growth, and on the other hand be a suitable scaffold for the growth of bone cells.

Chitosan-Based Hydrogels: Preparation, Properties, and Applications

Chitosan is a hydrophilic polysaccharide obtained by partial deacetylation of chitin, which is one of the most popular biopolymers. Chitosan is well known for its favorable properties including biocompatibility, biodegradability, antibacterial, and biological activity, as well as its renewable character. Thanks to those features chitosan’s popularity in various applications ranging from food industry to tissue engineering is constantly growing. The following chapter will more closely consider fabrication, properties, and specific applications of chitosan-based hydrogel networks. Methods for chitosan preparation will be summarized, followed by detailed characterization of chitosan properties. Strategies for their improvement and fabrication of chitosan derivatives will be discussed as well. Next, attention will be drawn to preparation of chitosanbased hydrogels via chitosan crosslinking. Both chemical and physical crosslinking methods will be considered with special emphasis on comparison between the two crosslinking methods and recent advancements in application of novel biocompatible crosslinkers. This chapter will also take a closer look at formation of stimuli-responsive (especially pHand temperature-sensitive systems) and injectable hydrogels. Utilization of chitosan hydrogels in tissue engineering will be highlighted together with different techniques for fabrication and construction of three-dimensional scaffolds. Finally, other applications of chitosan-based hydrogels and their composites will be summarized.

Biodegradable intramedullary nails reinforced with carbon and alginate fibers: In vitro and in vivo biocompatibility

Background: Commonly, intramedullary nails are made of nondegradable materials, and hence they need to be removed once the bone fracture is healed. We propose a novel composite material consisting of poly-L-lactide matrix modified with carbon and alginate fibers to be used for biodegradable intramedullary fixation. The aim of this study was to make in vitro and in vivo biocompatibility assessments. Methods: In the in vitro conditions, biocompatibility of biomaterials was compared using normal human osteoblasts. After 3 and 7 days, cytotoxicity, viability and proliferation tests were performed, as well as cell morphology and adhesion observations. In the in vivo experiments, Californian rabbits (approx. 9 months old) were used. The composite nails and controls (Kirschner wires) were used for fixation of distal femoral osteotomy. The evaluation was made on the basis of clinical observations, radiographs taken after 2, 4, 6 and 8 weeks post implantation, and macroscopic and histological observations. Results: Cell tests indicated that both modifiers had a positive influence on cell viability. Biodegradable composite nails led to bony union when used for fixation of distal diaphysis osteotomy in rabbits. Histological analysis showed that the initial focal necrosis should be fully compensated for by the osteoblast proliferation and trabeculae formation. Conclusions: Both in vitro and in vivo tests confirmed biocompatibility and potential applicability of novel biodegradable intramedullary nails modified with long carbon and alginate fibers for osteosynthesis of bone epiphysis.