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1

Nanocząstki w biokompozytach polimer – ceramika do regeneracji tkanki kostnej

Bartolewska Magdalena

Szkło i Ceramika

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2021

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R. 72, nr 4

28--30

PL

Medycyna regeneracyjna staje się szybko rozwijającą techniką w współczesnej biomedycynie. Coraz częściej na świecie są wykorzystywane nanocząstki do naprawiania i leczenia uszkodzonych komórek. Ten artykuł przeglądowy przedstawia wiedzę na temat kompozytów, składających się z polimeru oraz hydroksyapatytu, modyfikowanych nanocząstkami i ich zastosowaniami w medycynie regeneracyjnej.

EN

Regenerative medicine is becoming a rapidly developing technique in modern biomedicine. Nanoparticles are used increasingly to repair and heal damaged cells. The paper presents knowledge about the use of nanoparticles in the modification of polymer and hydroxyapatite composites and their applications in regenerative medicine.

2

Biomaterials in Regenerative Medicine: view of the Past & Vision for the future

Kirkpatrick Charles James

Engineering of Biomaterials

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2021

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Vol. 24, no. 163

7

EN

In the past two decades, the fields of Tissue Engineering (TE) and Regenerative Medicine (RegMed) have received important input from advances in stem cell research as well as in the biomaterial sciences, including new developments in composite materials and interactive polymer systems. In the latter, for example, biodegradable scaffolds and hydrogels can mimic essential characteristics of the extracellular matrix (ECM), which is the microenvironment of cells in their natural state in situ. Being able to simulate such cell-cell and cell-matrix interactions in vitro is important not only for testing new biomaterials, but also for understanding regenerative mechanisms after implantation. However, this is far from a trivial challenge, although it can be usefully assisted by employing co-culture models in three dimensions. The situation becomes even more complex, when novel biomaterials and strategies for regeneration are investigated in vivo. Testing in animals introduces namely a complexity which makes mechanistic interpretation of observations exceedingly difficult, if not impossible. Moreover, in the past the accepted norms in testing have generally involved, for example, implantation in healthy animals, although in reality most patients receive a biomaterial for a disease state. Thus, for in vivo models there is an acute need to develop relevant models of disease. Future developments must also address the challenges of understanding the effects of, for example, ageing, multi-morbidity and medication on tissue reactions at the implant interface. Such multifactorial considerations play a special role in the case of cancer patients. In the future, biomaterials and TE & RegMed will be increasingly influenced by the broadening interface with biotechnology. The latter is so vast that it is difficult to put its elements into a single presentation slide which an audience could read without binoculars and a prolonged time slot! However, the COVID-19 pandemic has focussed attention on the power of mRNA technology in modulating the body's immune system. It remains to be established how this technology could be adapted to control unwanted reactions at specific sites, for example, at a tissue-biomaterial interface. Returning to biotechnology as a driver of future progress, it seems highly likely that both major scientific branches of biomaterials, namely the materials sciences and the life sciences, will receive transforming impulses from advances in biotechnology. Fields such as artificial intelligence, green technology, robotics and nanotechnology underline just how diverse biotechnology is. In addition, this diversity stresses the essential role of interdisciplinarity and its implications for university teaching for future generations of materials and life scientists.

3

Current status and future prospects of genome-scale metabolic modeling to optimize the use of mesenchymal stem cells in regenerative medicine and biomaterials

Sigurjonsson Olafur E.

Engineering of Biomaterials

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2020

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Vol. 23, no. 158 spec. iss.

7

EN

Mesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after reimplantation. One aspect of extracorporeal growth that may be manipulated to optimize cell growth and differentiation is metabolism. The metabolism of MSCs changes during and in response to differentiation and immunomodulatory changes. MSC metabolism may be linked to functional differences but how this occurs and influences MSC function remains unclear. Understanding how MSC metabolism relates to cell function is however important as metabolite availability and environmental circumstances in the body may affect the success of implantation. Genome-scale constraint based metabolic modelling can be used as a tool to fill gaps in knowledge of MSC metabolism, acting as a framework to integrate and understand various data types (e.g., genomic, transcriptomic and metabolomic). These approaches have long been used to optimize the growth and productivity of bacterial production systems and are being increasingly used to provide insights into human health research. Production of tissue for implantation using MSCs requires both optimized production of cell mass and the understanding of the patient and phenotype specific metabolic situation. This review considers the current knowledge of MSC metabolism and how it may be optimized along with the current and future uses of genome scale constraint based metabolic modelling to further this aim.

4

Porównanie skuteczności różnych metod wprowadzania porów do biomateriału na bazie ceramiki hydroksyapatytowej

Syta E., Kazimierczak P., Stadnicka G., Pałka K., Ginalska G., Przekora A.

Materiały Ceramiczne

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2018

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T. 70, nr 2

89--101

PL

Wysoka makroporowatość biomateriału, która sprzyja procesowi angiogenezy, ma największy wpływ na dobrą osseointegrację implantu z kością pacjenta. W niniejszej pracy porównano skuteczność trzech różnych metod wprowadzania porów do biomateriału polimerowo-ceramicznego w celu wykorzystania go do zastosowań w medycynie regeneracyjnej kości. W ramach badań modelowy biomateriał zbudowany z agarozy i bioceramiki w postaci nanoproszku hydroksyapatytowego został wyprodukowany przy pomocy trzech alternatywnych metod z wykorzystaniem: 1. porogenów stałych (ang. porogen leaching, P-L), 2. gazu CO2 jako porogenu (ang. gas-foaming, G-F) i 3. procesu liofilizacji (ang. freeze-drying, F-D). Następnie porównano mikrostrukturę oraz porowatość otrzymanych biomateriałów. Wyniki badań wykazały, że biomateriał wytworzony metodą F-D posiada największą porowatość otwartą i całkowitą oraz charakteryzuje się obecnością porów zespolonych, które w warunkach ustrojowych stymulują proces angiogenezy. Ponadto technika F-D jako jedyna umożliwia równomierną dystrybucję porów w obrębie całej próbki.

EN

High macroporosity of the biomaterial, which is crucial for the angiogenesis process, has a great impact on good osseointegration of the implant with patient bone. In this study, effectiveness of three various methods for pore introduction into polymer-ceramics biomaterial for potential bone regenerative medicine applications was compared. Within the research, a model biomaterial made of agarose and bioceramics in the form of nanohydroxyapatite powder was produced using: (i) a porogen leaching method (P-L), (ii) CO2 gas as a porogen (gas-foaming method, G-F), and (iii) the lyophilisation process (freeze-drying method, F-D). Then, the microstructure and porosity of fabricated biomaterials were compared. Obtained results demonstrated that the biomaterial produced by the F-D method possesses the highest open and total porosity as well as is characterized by the presence of network of interconnected pores, which in physiological conditions stimulates the angiogenesis process. Moreover, F-D technique is the only one that allows for uniform distribution of pores within whole volume of the sample.

5

The significance of the nanostructural components on the properties of the nanoengineering materials

Dobrzański L. A.

Journal of Achievements in Materials and Manufacturing Engineering

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2018

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Vol. 88, nr 2

55--85

EN

Purpose: In the paper, the own original achievements and a mature view of the current development of advanced nanotechnology materials are presented. Design/methodology/approach: The paper should be treated as an auto-review of the own research in the area. The paper is preceded by a short historical sketch and the development of the concept and meaning of nanotechnology and nanostructured materials. Respectively, the following issues are described: the nanocomposites containing carbon or halloysite nanotubes, graphene and metallic nanowires, nanostructured coatings and surface zones of engineering materials, a creation of the nanometric components of the structure of massive materials, nanocomposite materials designed mainly for use in regenerative medicine and regenerative dentistry. Practical implications: In final remarks, the attention is paid to applications of nanotechnology in many products sought on the market and improve their properties and applicability.

6

Application of polymer- and graphene- based materials in biomedical research

Sekuła M., Domalik-Pyzik P., Noga S., Karnas E., Kosowska K., Hunger M., Złocista-Szewczyk N., Jagiełło J., Lipińska L., Pielichowska K., Chłopek J., Zuba-Surma E.

Engineering of Biomaterials

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2018

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Vol. 21, no. 148

66

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The new generation of the biologicalengineering materials for applications in medical and dental implant-scaffolds

Dobrzański L. A., Dobrzańska-Danikiewicz A. D., Czuba Z. P., Dobrzański L. B., Achtelik-Franczak A., Malara P., Szindler M., Kroll L.

Archives of Materials Science and Engineering

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2018

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Vol. 91, nr 2

56--85

EN

Purpose: The publication aims to find the relationship between the proliferation of surface layers of living cells and the deposition of thin atomic layers deposition ALD coatings on the pores internal surfaces of porous skeletons of medical and dental implant-scaffolds manufactured with the selective laser deposition SLS additive technology using titanium and Ti6Al4V alloy. Design/methodology/approach: The extensive review of the literature presents the state-of-the-art in the field of regenerative medicine and tissue engineering. General ageing of societies, increasing the incidence of oncological diseases and some transport and sports accidents, and also the spread of tooth decay and tooth cavities in many regions of the world has taken place nowadays. Those reasons involve resection of many tissues and organs and the need to replace cavities, among others bones and teeth through implantation, more and more often hybridized with tissue engineering methods. Findings: The results of investigations of the structure and properties of skeleton microporous materials produced from titanium and Ti6Al4V alloy powders by the method of selective laser sintering have been presented. Particularly valuable are the original and previously unpublished results of structural research using high-resolution transmission electron microscope HRTEM. Particular attention has been paid to the issues of surface engineering, in particular, the application of flat TiO2 and Al2O3 coatings applied inside micropores using the atomic layers deposition ALD method and hydroxyapatite applied the dip-coating sol-gel method, including advanced HRTEM research. The most important part of the work concerns the research of nesting and proliferation of live cells of osteoblasts the hFOB 1.19 (Human ATCC - CRL - 11372) culture line on the surface of micropores with surfaces covered with the mentioned layers. Research limitations/implications: The investigations reported in the paper fully confirmed the idea of the hybrid technology of producing microporous implants and implant-scaffolds to achieve original Authors’ biological-engineering materials. The surface engineering issues, including both flat-layered nonorganic coatings and interactions of those coverings with flat layers of living cells, play a crucial role. Originality/value: Materials commonly used in implantology and the most commonly used materials processing technologies in those applications have been described. Against that background, the original Authors' concept of implant-scaffolds and the application of microporous skeleton materials for this purpose have been presented.

8

Metallic skeletons as reinforcement of new composite materials applied in orthopaedics and dentistry

Dobrzański L. A., Dobrzańska-Danikiewicz A. D., Czuba Z. P., Dobrzański L. B., Achtelik-Franczak A., Malara P., Szindler M., Kroll L.

Archives of Materials Science and Engineering

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2018

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Vol. 92, nr 2

53--85

EN

Purpose: The article concerns the development of completely new groups of composite materials that can be used to produce functional replacements for damaged bones or teeth. Design/methodology/approach: A selective laser sintering was used to produce the reinforcement of those materials from titanium and its Ti6Al4V alloy in the form of skeletons with pores with adjustable geometric features. The matrix of those materials is either air or crystallised from the liquid AlSi12 or AlSi7Mg0.3 alloys condition after prior vacuum infiltration or human osteoblast cells from the hFOB 1.19 (Human ATCC - CRL - 11372) culture line. Findings: The porous material may be used for the non-biodegradable scaffold. After implantation into the body in the form of an implant-scaffold one, it allows the natural cells of the patient to grow into the pores of the implant, and it fuses with the bone or the appropriate tissue over time. The essential part of the implant-scaffold is the porous part inseparably connected with the core of solid materials. Into pores can grow living cells. Research limitations/implications: Biological-engineering composite materials in which natural cells were cultured in the pores in the laboratory next are combined as an artificial material with the natural cells of the patient in his/her body. Practical implications: The hybrid technologies of the all group of those materials were obtained and optimised. Numerous structure research was carried out using the most modern research methods of contemporary materials engineering, and mechanical tests and biological research involving the cultivation of natural cells were realised. Originality/value: The results of the research indicate the accuracy of the idea of implementing a new group of biological-engineering materials and the wide possibilities of their application in regenerative medicine.

9

Rusztowania (scaffolds) stosowane w medycynie regenaracyjnej

Chaberska A., Rosiak P., Kamiński Z. J., Kolesińska B.

Wiadomości Chemiczne

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2017

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[Z] 71, 3-4

263--286

EN

The presence of three dimensional support is indispensable condition for successful regeneration of the tissue. In the absence of natural scaffold, or absence of its artificial substitute, regeneration is not possible. The advantage of natural building blocks to create new scaffolds results from the requirements of the materials structures used for tissue regeneration: biocompatibility, biodegradability, lack of cytotoxicity and desirable mechanical properties. Application of these building blocks for the preparation of three dimensional materials should ensure completely biocompatibility of the temporary extracellular matrix equivalent, thus offering construct resembling a natural milieu for the cells and finally regeneration of tissues. These include framework with elements stimulating adhesion of in vitro grown cells, growth factors, hormones and vitamins offered as a completed ingredients in the commercially available culture media. 3D frameworks applied for cell growing should facilitate formation of required tissue shape and size as well as appropriate functioning of the cells. The key factor for the successful regeneration of tissues is the function of the scaffold determining the environment for growing cells, directing proliferation and regulating differentiation processes. The basic feature of the cellular scaffold, determining its functioning is porosity. Pore diameter and their abundance consists a critical factor for penetration of cells into the interior of the implant and finally for successful regeneration of damaged tissue. The progress of tissue regeneration in vitro depends on the presence of cytokines and growth factors, which are controlling cell differentiation process. Nowadays neither of implant material offered on the market has a property comparable to the natural tissue. However, there are many reports presenting preliminary experiments conducted towards attaining novel supports for regenerative medicine derived from peptides and formed by their self-organization. The most advanced of them are known under trade name PuraMatrix, which recently were applied for the regeneration of soft tissues. However, due to tendency of this materials for hydrogels formation, characteristic for them are disadvantageous mechanical properties. The alternative approach based on application of native ECM proteins was also taken into consideration. The weak points of this materials are the susceptibility of proteins towards proteolytic enzymes and theirs immunogenic properties. The diversity of peptide modules give the opportunity to design and synthesize a variety of biomaterials that mimic the structural complexity of the natural ECM.

10

Fabrication of Pure Electrospun Materials from Hyaluronic Acid

Pabjańczyk-Wlazło E., Krucińska I., Chrzanowski M., Szparaga G., Chaberska A., Kolesińska B., Komisarczyk A., Boguń M.

Fibres & Textiles in Eastern Europe

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2017

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Vol. 25, no. 3 (123)

45--52

EN

The aim of the research was to develop optimal conditions for manufacturing materials based on hyaluronic acid by the electrospun method. The studies were composed of three stages: the process of selection of the optimal solvent (mixture of solvents), the molecular weight of hyaluronic acid, and the concentration of biopolymer in the spinning solution. The influence of variable parameters on the rheological properties of the spinning solutions and electrospinning trails was tested. Depending on the electrospinning regime applied, the fibers obtained were characterised by a diameter of the order of 20 to 400 nm. As a result of the development works presented, an optimal molecular weight of the polymer, its concentration and system of solvents were determined, together with process parameters, ensuring a stable electrospinning process and relatively homogeneous nanofibers. Additionally studies on the residues of solvents used during electrosun formation were done and parameters of drying of the final materials were examined. This approach (verification of the presence of organic solvent residue in the nanofibrous formed) is important for the suitability of nanofibres as scaffolds for regenerative medicine. This study provides an opportunity for the understanding and identification of process parameters, allowing for predictable manufacturing nanofibers based on natural biopolymers, which makes it tremendously beneficial in terms of customisation.

PL

Celem badań było opracowanie optymalnych warunków otrzymywania nanowłókien z kwasu hialuronowego. Badania obejmowały następujące etapy realizacji pracy: proces doboru optymalnego rozpuszczalnika dla polimeru oraz dobór masy cząsteczkowej kwasu hialuronowego. Zbadano właściwości reologiczne roztworów oraz wpływ zmiennych parametrów procesowych na strukturę mikroskopową włókien. W zależności od zastosowanych parametrów elektroprzędzenia otrzymane włókna charakteryzowały się średnią rzędu od 20 do 400 nm. Dodatkowo przeprowadzono badania dotyczące pozostałości rozpuszczalników stosowanych w przygotowaniu roztworów przędzalniczych, co jest istotne z punktu widzenia wykorzystania tych materiałów w obrębie medycyny regeneracyjnej.

11

Modification of PLGA microspheres’ microstructure for application as cell carriers in modular tissue engineering

Mielan B., Krok-Borkowicz M., Pielichowska K., Pamuła E.

Engineering of Biomaterials

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2017

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Vol. 20, no. 140

7--11

EN

Microspheres (MS) made of resorbable polymer have been proposed as a cell growth support. They may be assembled to form cell constructs or be suspended in hydrogels allowing injection into injury location. High relative surface area of MS provides more efficient cell culture environment than traditional culture on flat substrates (multiwell plates, Petri dishes). In addition, MS structure, topography and surface chemistry can be modified to promote cell adhesion and proliferation. The aim of this study was to obtain resorbable poly(L-lactide-co-glycolide) (PLGA) MS and to modify their properties by changing manufacturing conditions of the oil-in-water emulsification to better control structural and microstructural properties of MS and their biological performance. To this end, water phase was modified by addition of NaCl to change ionic strength, while oil phase by addition of polyethylene glycol (PEG). Microstructural and thermal properties were assessed. Cytocompatibility tests and cell cultures with MG-63 cells were conducted to verify potential relevance of MS as cell carriers. The results showed that it is possible to obtain cytocompatible MS by oil-in-water emulsification method and to control diameter, porosity and crystallinity of MS with the use of additives to oil and/or water phases without negative changes in MS cytocompatibility. The results prove that modification of both phases make it possible to produce MS with desired/controllable properties like surface topography, porosity and crystallinity.

12

Microstructure of chitosan-based, ZnO-doped antibacterial composite

Ciołek L., Biernat M., Jaegermann Z., Zaczyńska E., Czarny A., Jastrzębska A., Olszyna A.

Engineering of Biomaterials

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2017

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Vol. 20, no. 143 spec. iss.

18

13

Development and optimization of myocardial tissue culture in ovo

Hotowy A., Sawosz E., Grodzik M., Wierzbicki M., Kutwin M., Jaworski S., Chwalibog A.

Engineering of Biomaterials

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2017

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Vol. 20, no. 143 spec. iss.

54

14

Aromatic peptides as components of potential scaffolds for regenerative medicine

Strzempek W., Menaszek E., Dziadek M., Stodolak-Zych E., Boguń M., Kolesińska B.

Engineering of Biomaterials

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2017

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Vol. 20, no. 143 spec. iss.

74

15

Design and preclinical validations of polysaccharide-based nano/micro/macrosystems for tissue engineering and molecular imaging

Letourneur D.

Engineering of Biomaterials

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2016

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Vol. 19, no. 138 spec. iss.

9

EN

This presentation intends to present polysaccharidebased matrices for regenerative medicine and as drug delivery systems and targeted contrast agents for molecular imaging. One main challenge of tissue engineering is to create an optimal environment for growing therapeutic cells to regenerate damaged tissues. This environment can be reconstituted by using 3D matrices, in which cells can be organized into a tissue-like structure. We have prepared polysaccharide-based porous matrices having controlled pores and porosity for several cell types. These porous hydrogels made of natural biodegradable and biocompatible polysaccharides have architectural characteristics adapted to the cell culture in 3D. We have developed them to different shapes and sizes. Further studies have demonstrated the performance of these matrices for tissue repair in vitro as well as in small and large animals. Examples for heart, vessel, and bone will be presented. Moreover, polysaccharide-based nano and microsystems were also designed and used for the imaging of cardiovascular pathologies as targeted contrast agents for molecular imaging. Examples will be provided using several types of imaging modalities for thrombus detection. We will also present how to use nanomaterials for regenerative medicine. Indeed, adhesion by aqueous nanoparticle solutions can be used in vivo to achieve rapid and strong closure and healing of deep wounds in rat skin and liver. Nanoparticles can also be used to fix polymer membranes to tissues even in the presence of blood flow, such as occurring after liver resection, yielding permanent hemostasis within a minute. Furthermore, medical devices and tissue engineering constructs could be fixed to organs such as a beating heart.

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The concept of biologically active microporous engineering materials and composite biological-engineering materials for regenerative medicine and dentistry

Dobrzański L. A.

Archives of Materials Science and Engineering

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2016

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Vol. 80, nr 2

64--85

EN

Purpose: The concept presented in this study proposes indirect solutions, both, rigid ones involving high strength and transmission of high mechanical loads, and ones which are elastic, thin and light as fog, when a very light dressing supplying living cells is applied to an extensive wound, e.g. on skin, in a way ensuring their fast fusion with the defected surface of body. They are proposed implant-scaffolds, i.e. rigid devices composed of a solid metal core and a surface or transition porous zone into which living cells may grow. The pores are so small that hair or even a very thin needle can be placed there. The interior of such openings, extending along the entire part of material, needs to be covered from the inside with a very thin coating which can be accepted by living cells so that they can develop in such conditions and penetrate such openings deep inside. Design/methodology/approach: The material solutions proposed in the study result from a synergy of methods of technical sciences, including materials engineering and chemical sciences, in consistency with the adopted author’s assumptions, but, in particular, depending on the specificity of clinical conditions and biological sciences, also tissue engineering, in the context of medical sciences, including tissue therapy, require a multiaspect state-of-the-art analysis and the resulting specific scientific problems which should be solved and their pioneering character. Taking into consideration the lack of references in the literature to the overall analysis of the issue, separate aspects are analysed further in this study concerning biologically active cellular structures and a substrate with an engineering composite material matrix used for scaffolds and newly developed implant-scaffolds. Findings: In consideration of the principal research intention of the presented research concept, pertaining to the development of hybrid and multilayer biological-engineering composite materials, including rigid and elastic ones, composed not only of biologically active cellular structures, the state-of-the-art of which is presented earlier, but also of a substrate with an engineering material matrix, with an optimally selected type, chemical composition and a nanometric structure, fulfilling a carrier function, and in fact a scaffold for biological structures required to have an appropriate array of mechanical properties and rigidity, allowing applications in therapeutic conditions, as well as physiochemical properties, permitting to fully control the behaviour of the whole biological- engineering composite material upon achieving the therapeutic aims defined by medical reasons, it is necessary to consider the material and technological aspects allowing to accomplish the abovementioned assumptions in the current state of technology. Practical implications: Despite obvious technological progress seen in the recent period in the fabrication of cell-based products and in cell-based therapies, it should be acknowledged that therapies based on implantable devices together with the participation of growing cells, and especially the mass technological processes required by such therapies, are still in a relatively incipient phase of technological development, leaving a lot of space for original and pioneering basic research. The basic research performed in the study will represent a solid basis for undertaking application works in the future, allowing to fabricate a new generation of concrete products unknown today, which will find their application in regenerative medicine and dentistry for treating various internal and external disorders associated with, e.g. burning, healing or severe wounds and injuries, removal of consequences of oncological or post-injury disorders. Originality/value: The primary scientific aim of the presented research concept is to verify a research thesis that it is possible and relevant to develop multilayer biological-engineering composite materials having clinical readiness, partially artificial ones, using Selective Laser Sintering (SLS), to fabricate microporous rigid titanium and titanium alloy skeletons or for polymer nanofiber electrospinning to produce microporous elastic mats, and partially biological ones consisting of living cells filling the appropriately prepared pores in the mentioned microporous materials. Cognitive aspects concern the recognition of phenomena and mechanisms associated with fabrication of the so understood biologically active microporous engineering material being, in essence, a biological-engineering composite material, and of surface phenomena and mechanisms taking place between individual layers of this unique material and their influence on manufacturing processes, both, in the engineering as well as biological part, and on the behaviour of particular layers and joint zones between such layers during material fabrication, as well as in conditions simulating therapy preparation and duration, and alternatively during the non-destructive separation of cellular structures from a substrate from a composite engineering material substrate on which cells are grown, but already after fulfilling the intended therapeutic function, if the material is not permanently left in the organism.

17

Biodegradable and antimicrobial polycaprolactone nanofibers with and without silver precipitates

Dobrzański L. A., Hudecki A., Chladek G., Król W., Mertas A.

Archives of Materials Science and Engineering

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2015

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Vol. 76, nr 1

5--26

EN

Purpose: The purpose of the paper is to present the results of own researches, including the study of the structure and the properties of new obtained single- and doublecomponent polycaprolactone polymer nanofibers as well as of composite nanofibers with and without silver precipitates produced by electrospinning including the results of biological research, proving the usefulness of the newly developed nano-engineering materials and their applicability in regenerative medicine, as well as tissue engineering. Design/methodology/approach: On the basis of the data available from the fundamental literature and based on the criteria of potential and attractiveness, polycaprolactone was selected for research from among a number of polymer materials, using a method of procedural benchmarking and weighted scores. The obtained nanomaterials undergone the following examinations to confirm the assumed aim of the work: infrared spectroscopy FTIR, Wide-angle X-ray scattering (WAXS), BET, Langmuir specific surface area and DTF porosity assessed with the gas adsorption method, in a transmission electron microscope (TEM), a scanning electron microscope (SEM), a fluorescence microscope, antibacterialness and antifungalness investigations and examinations of biological properties in vitro. Findings: The applicability of polymer fibers in medicine depends on biocompatibility and non-toxicity of the applied material, which is influenced by the chemical purity of the materials applied and the toxicity of the input solvents. The potential toxicity of nanofibers should therefore be eliminated, starting with selection of materials used for obtaining solutions. Many other factors fundamental for the quality and properties of polycaprolactone nanofibers need to be taken into account to create single- and doublecomponent and composite nanofibers. Practical implications: The obtained composite materials, due to their non-toxicity resulting from the components applied, including solvents, bacteriocidity and bioactivity, may find their applications in tissue engineering as membranes in controlled regeneration of bone tissue, as carriers of medicinal agents in bone surgery, as implantable surgical meshes and as scaffolds for a tissue culture. In turn, the composite core-shell nanofibers, by combining the antibacterial properties of the coating with bioactive properties of the core, are attractive materials for three-dimensional tissue scaffold. Such materials can be used as a carrier of medicine, a treatment of hard healing wounds, invasive surgery, neurosurgery, as substrate for the culturing of a retina, material to reconstruct nerves and in dentistry or oncology, to replace the natural tissue removed because of a cancer with the possibility of applying a therapeutic agent, e.g., an antibiotic or a medicine used in cancer therapies, released after the dissolution of the coating of nanofibers. Originality/value: The present paper is the original report from a personal own research and explains the concept and scope of own research of a new obtained single- and doublecomponent polycaprolactone polymer nanofibers as well as of composite nanofibers produced by electrospinning for application in regenerative medicine, the presentation of technological conditions and methodology of own research into polymer nanofibers, and above all very detailed description of the results of own investigations

18

Applications of newly developed nanostructural and microporous materials in biomedical, tissue and mechanical engineering

Dobrzański L. A.

Archives of Materials Science and Engineering

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2015

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Vol. 76, nr 2

53--114

EN

Purpose: The purpose of the paper is to present the main results of own research in 3 principal aspects indicating that the research is up to date and modern. This relates to nanotechnologies, modern biomedical materials and rapid manufacturing techniques used for the production of, in particular, microporous materials applied for medical and dental purposes. The paper comprises the explanation of structural mechanisms and phase transformations taking place in newly created engineering nanostructural and microporous materials under the influence of the applied, advanced technological processes newly developed, and especially nanotechnological processes, using the most modern scientific and research equipment being at disposal of modern materials engineering, in particular with the common use of high-resolution transmission electron microscopy (HRTEM). The results of investigations into the formation of the structure and surface properties results according to a different thickness scale of coatings or surface zone, from several hundred nanometres to several millimetres, are presented in the paper, including PVD and CVD coatings and laser treated surface on the steels and light alloys substrates. The paper also describes the nanostructural effects in solid materials, and especially the counteraction of cracking of new-developed high-manganese austenite steels Fe-Mn-Si-Al by twinning or/and martensitic transformation induced by the cold plastic deformation. The article also outlines the results of research of the development of special micro and nanocomposite materials designed mainly for use in regenerative medicine and regenerative dentistry. The studies of the structure and the properties of newly obtained materials and originally developed technologies are included to present the author’s contribution into materials science, nanotechnology, surface engineering and biomedical engineering including the usefulness of the newly developed nanoengineering materials and their applicability, in particular, in regenerative medicine, as well as tissue engineering. The described outcomes of the research constitute a basis for creating, apart from rigid porous implant-scaffolds, an innovative generation of rigid and elastic biological-engineering composite materials for regenerative medicine. Design/methodology/approach: The article discusses the key aspects of own research performed over the last decade in scope of nanotechnologies, modern biomedical materials and rapid manufacturing techniques used for the fabrication of, in particular, microporous materials applied for medical and dental purposes. The conditions for the performance of the research according to the scope mentioned were ensured by implementation of investment projects for constructing and equipping research and didactic laboratories in scope of nanotechnology, technologies of material processes and computational materials science, including LANAMATE (2010-2014) and MERMFLEG (2010-2013), and also BIOFARMA (2010-2012). Practical implications: The obtained materials and technologies are of high practical importance, which was confirmed in many cases with the results of laboratory tests and investigations at a semi-technical scale, and in some cases with the initiation of implementation works. The results of research in scope of bioengineering and dental engineering may find their applications in tissue engineering, in bone surgery, for threedimensional tissue scaffolds and in dentistry or oncology, to replace the natural tissue removed because of a cancer with the possibility of applying a therapeutic agent. Originality/value: The present paper is the original report from a personal own research and explains the concept, scope and results of own research of a new obtained microporous and nanostructural materials and coatings, including hybride solid-porous products and newly obtained materials processing and additive technologies. Some of the mentioned research results are protected by patents or patent applications, and many of them were awarded over 60 prizes and medals at international fairs of innovation, invention and rationalisation in many countries.

19

Stem cells and their derivatives – hopes and challenges in regenerative medicine

Zuba-Surma E. K.

Engineering of Biomaterials

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2014

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Vol. 17, no. 128-129

102

EN

Major goals of contemporary regenerative medicine focus on improvement of irreversible damage of multiple organs and tissues by employing several approaches including recent achievements of cellbased therapies and tissue engineering. Several types of stem cells (SCs) such as bone marrow (BM)- derived mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs) as well as SCs with multi- and pluripotent characteristics (PSCs) have been postulated as potential source of cells for therapy. Recently, embryonic stem cells (ESCs) and so called induced pluripotent stem cells (iPS cells) representing “genetically induced” SCs with high differentiation potential, have brought great hope to the field of regenerative medicine and clinical applications. When combined with modern accomplishments of tissue engineering including biocompatible carriers and scaffolds, SCs become leading targets for cell -based regenerative applications. Although the variety of stem/ progenitor cells have been applied in experimental therapies of several organs injuries, there is still no agreement in scientific and clinical world which subpopulation/s of cells would be the most efficient in such treatment. Moreover, multiple obstacles needs to be overcome prior to optimal application of SCs in regeneration including optimization of ex vivo isolation and expansion conditions or limiting vast adverse features of some SC fractions such as teratogenic potential of ESCs and iPS cells. Recently, stem cell- derived bioactive components such as cellular microvesicles (MVs) are postulated to play important role in mediating SC activity following transplantation. MVs representing bioactive components carrying SC- derived transcripts (mRNA, miRNA), proteins, enzymes and receptors may participate in tissue regeneration via stimulation of endogenous repair mechanism by activating endogenous target cells in damaged organs. Thus, the newest trends in regenerative medicine would focus not only on combined applications of biocompatible materials with SC subpopulations, but also with their bioactive acellular components including microvesicles. Unquestionably, successful applications of stem/ progenitor cells and their derivatives in regenerative medicine would need to be safe, ethically acceptable and therapeutically efficient. Sources and application protocols for such optimal stem cell therapy are still being optimized and need scientific discussion.

20

Biomaterial-based regenerative medicine: challenges & opportunities

Kirkpatrick C. J.

Engineering of Biomaterials

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2014

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Vol. 17, no. 128-129

1--2

EN

For the author there are three major challenges in Regenerative Medicine (RegMed), namely to develop strategies which are translatable, materials which are functional and methods which are predictive. New strategies in RegMed depend on a concerted interdisciplinary effort between the exact and engineering sciences on the one side and the life sciences on the other. As cells synthesize and reside in an extracellular matrix (ECM), which they remodel, a main focus of biomaterial research is the development of injectable, bioresorbable hydrogels containing biological signals which could be released by tissue responses. These interactive materials will certainly increase in importance in the future. However, a major challenge is how to combine them, for example, in composites with load-bearing capacity relevant for human applications. Where synthetic materials such as metals are still essential, as in orthopaedics and traumatology, there is the possibility of adding such responsive materials as coatings to the bulk material. The use of decellularized matrix is also part of the bioinspired approach to developing biomaterials. In the life sciences great effort is being invested in understanding the so-called „regenerative niche“, which differs from tissue to tissue. Great progress made in stem cell biology has opened up new vistas on the possibility to target a regenerative niche. Cell-cell and cell-matrix interactions remain a central element of this activity. One of the paradigm shifts we need to master is the step from what is usual even in complex cell biological models, namely the use of purely physiological conditions, to a more realistic situation as would be found in the clinical setting. Thus, we need to understand regeneration in hostile environments, which include post-trauma, cancer and multimorbidity. This will be discussed with examples from the author’s own research. One of the important in vitro methods to investigate the mechanisms involved in regeneration is the use of coculture systems with relevant human cells, usually on tissue culture plastic and, as knowledge progresses, on more complex 3D biomaterial scaffolds. As major limiting factors in bone regeneration are the speed and extent of vascularization, we have established human osteoblast (pOB)-endothelial cell (EC) cocultures to study cellular crosstalk and its possible use for translational strategies [1,2]. Concerning the background, if two cell populations, that is, human pOB and human dermal microvascular EC (HDMEC), are seeded as cell suspensions on an open porous biomaterial scaffold, such as can be made from microfibres of the silk protein fibroin, the two cell types will interact in such a way that lumen-containing, capillary-like structures (CLS) will form as a vascular network [3]. Further molecular studies on the cellular crosstalk revealed that the EC induce an upregulation of growth factor and matrix production in pOB, such as VEGF and collagen type I resp. The EC then respond to these signals by promoting the angiogenic phenotype [4,5]. The following additional approaches have been adopted to study CLS formation: use of early embryonic signals, such as sonic hedgehog (shh), to accelerate both osteoand angiogenesis [6,7], use of intermittent hypoxia, but not constant hypoxia, to promote vascular sprout formation, and study of possible stimulatory roles for macrophages in the bone regenerative niche [8]. How this is investigated in coculture models will be discussed in the context of future evelopments. Naturally, all phenomena from in vitro studies require proof of concept in relevant in vivo models, as only this approach can lead to a translational perspective. Thus, we were able to demonstrate that these in vitro pre-formed vessels can rapidly become inosculated, that is, incorporated into the pre-existing microcirculation of host tissue in a subcutaneous implantation model [9]. The major role of the osteoblasts as a natural „drug delivery system“ was shown by the fact that host vascular response can be stimulated by these cells even in the absence of a pre-cultivation with endothelial cells [10]. A further aspect offering a promising perspective for the future is NanoMedicine, which uses advances in nanotechnology for medical applications. For reasons of time this will not be addressed in the context of the presentation. In conclusion, biomaterials, especially so-called responsive biomaterials, are an essential element of modern regenerative medicine, and must be accompanied by state of the art life sciences, from cell and molecular biology to good clinical practice. To achieve this the multidisciplinary approach is a conditio sine qua non.