Tomasz Kowalczyk, Ph.D., Eng.

Laboratory of Polymers and Biomaterials (SPPiB)
position: assistant
telephone: (+48) 22 826 12 81 ext.: 423
room: 328
e-mail: tkowalcz
personal site: http://pmbm.ippt.pan.pl/web/Tomasz_Kowalczyk

Doctoral thesis
2002-07-02Badania nad syntezą i polimeryzacją alifatycznych węglanów cyklicznych  (PW)
supervisor -- Gabriel Andrzej Rokicki, PW
1232 
Supervision of doctoral theses
1.2015-02-03
co-supervisor
Nakielski Paweł  
(IBIB PAN)
Systemy uwalniania leków oparte na nanowłóknach1082
 

Recent publications
1.Jundziłł A., Pokrywczyńska M., Adamowicz J., Kowalczyk T., Nowacki M., Bodnar M., Marszałek A., Frontczak-Baniewicz M.M., Mikułowski G., Kloskowski T., Gatherwright J., Drewa T., Vascularization Potential of Electrospun Poly(L-Lactide-co-Caprolactone) Scaffold: The Impact for Tissue Engineering, Medical Science Monitor, ISSN: 1643-3750, DOI: 10.12659/MSM.899659, Vol.23, pp.1540-1551, 2017
Abstract:

BACKGROUND:
Electrospun nanofibers have widespread putative applications in the field of regenerative medicine and tissue engineering. When compared to naturally occurring collagen matrices, electrospun nanofiber scaffolds have two distinct advantages: they do not induce a foreign body reaction and they are not at risk for biological contamination. However, the exact substrate, structure, and production methods have yet to be defined.
MATERIAL AND METHODS:
In the current study, tubular-shaped poly(L-lactide-co-caprolactone) (PLCL) constructs produced using electrospinning technology were evaluated for their potential application in the field of tissue regeneration in two separate anatomic locations: the skin and the abdomen. The constructs were designed to have an internal diameter of 3 mm and thickness of 200 μm. Using a rodent model, 20 PLCL tubular constructs were surgically implanted in the abdominal cavity and subcutaneously. The constructs were then evaluated histologically using electron microscopy at 6 weeks post-implantation.
RESULTS:
Histological evaluation and analysis using scanning electron microscopy showed that pure scaffolds by themselves were able to induce angiogenesis after implantation in the rat model. Vascularization was observed in both tested groups; however, better results were obtained after intraperitoneal implantation. Formation of more and larger vessels that migrated inside the scaffold was observed after implantation into the peritoneum. In this group no evidence of inflammation and better integration of scaffold with host tissue were noticed. Subcutaneous implantation resulted in more fibrotic reaction, and differences in cell morphology were also observed between the two tested groups.
CONCLUSIONS:
This study provides a standardized evaluation of a PLCL conduit structure in two different anatomic locations, demonstrating the excellent ability of the structure to achieve vascularization. Functional, histological, and mechanical data clearly indicate prospective clinical utilization of PLCL in critical size defect regeneration.

Keywords:

Polymers, Regenerative medicine, Tissue Engineering, Tissue Scaffolds, Urinary Diversion

Affiliations:
Jundziłł A.-other affiliation
Pokrywczyńska M.-other affiliation
Gatherwright J.-University Hospitals – Case Medical Center (US)
Drewa T.-Nicolaus Copernicus University (PL)
Adamowicz J.-Nicolaus Copernicus University (PL)
Kowalczyk T.-IPPT PAN
Nowacki M.-other affiliation
Bodnar M.-Nicolaus Copernicus University (PL)
Marszałek A.-Nicolaus Copernicus University (PL)
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Mikułowski G.-IPPT PAN
Kloskowski T.-other affiliation
2.Adamowicz J., Pokrywczyńska M., Tworkiewicz J., Kowalczyk T., van Breda S.V., Tyloch D., Kloskowski T., Bodnar M., Skopińska-Wiśniewska J., Marszałek A., Frontczak-Baniewicz M.M., Kowalewski T.A., Drewa T., New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology, PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0146012, Vol.11, No.1, pp.e0146012-1-20, 2016
Abstract:

Objective
Due to the capacity of the amniotic membrane (Am) to support re-epithelisation and inhibit scar formation, Am has a potential to become a considerable asset for reconstructive urology i.e., reconstruction of ureters and urethrae. The application of Am in reconstructive urology is limited due to a poor mechanical characteristic. Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance, without affecting its unique bioactivity profile. This study evaluated biocomposite material composed of Am and nanofibers as a graft for urinary bladder augmentation in a rat model.

Material and Methods
Sandwich-structured biocomposite material was constructed from frozen Am and covered on both sides with two-layered membranes prepared from electrospun poly-(L-lactide-co-E-caprolactone) (PLCL). Wistar rats underwent hemicystectomy and bladder augmentation with the biocomposite material.

Results
Immunohistohemical analysis (hematoxylin and eosin [H&E], anti-smoothelin and Masson’s trichrome staining [TRI]) revealed effective regeneration of the urothelial and smooth muscle layers. Anti-smoothelin staining confirmed the presence of contractile smooth muscle within a new bladder wall. Sandwich-structured biocomposite graft material was designed to regenerate the urinary bladder wall, fulfilling the requirements for normal bladder tension, contraction, elasticity and compliance. Mechanical evaluation of regenerated bladder wall conducted based on Young’s elastic modulus reflected changes in the histological remodeling of the augmented part of the bladder. The structure of the biocomposite material made it possible to deliver an intact Am to the area for regeneration. An unmodified Am surface supported regeneration of the urinary bladder wall and the PLCL membranes did not disturb the regeneration process.

Conclusions
Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance without affecting its unique bioactivity profile.

Keywords:

Bladder, Smooth muscles, Muscle regeneration, Bionanotechnology, Renal system, Urothelium, Urology, Nanomaterials

Affiliations:
Adamowicz J.-Nicolaus Copernicus University (PL)
Pokrywczyńska M.-other affiliation
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Kowalewski T.A.-IPPT PAN
Drewa T.-Nicolaus Copernicus University (PL)
Tworkiewicz J.-other affiliation
Kowalczyk T.-IPPT PAN
van Breda S.V.-University of Pretoria (ZA)
Tyloch D.-other affiliation
Kloskowski T.-other affiliation
Bodnar M.-Nicolaus Copernicus University (PL)
Skopińska-Wiśniewska J.-other affiliation
Marszałek A.-Nicolaus Copernicus University (PL)
3.Noszczyk B.H., Kowalczyk T., Łyżniak M., Zembrzycki K., Mikułowski G., Wysocki J., Kawiak J., Pojda Z., Biocompatibility of electrospun human albumin: a pilot study, Biofabrication, ISSN: 1758-5082, DOI: 10.1088/1758-5090/7/1/015011, Vol.7, pp.015011-1-11, 2015
Abstract:

Albumin is rarely used for electrospinning because it does not form fibres in its native globular form. This paper presents a novel method for electrospinning human albumin from a solution containing pharmaceutical grade protein and 25% polyethylene oxide (PEO) used as the fibre-forming agent. After spontaneous cross-linking at body temperature, with no further chemicals added, the fibres become insoluble and the excess PEO can be washed out. Albumin deposited along the fibres retains its native characteristics, such as its non-adhesiveness to cells and its susceptibility for degradation by macrophages. To demonstrate this we evaluated the mechanical properties, biocompatibility and biodegradability of this novel product. After subcutaneous implantation in mice, albumin mats were completely resorbable within six days and elicited only a limited local inflammatory response. In vitro, the mats suppressed cell attachment and migration. As this product is inexpensive, produced from human pharmaceutical grade albumin without chemical modifications, retains its native protein properties and fulfils the specific requirements for anti-adhesive dressings, its clinical use can be expedited. We believe that it could specifically be used when treating paediatric patients with epidermolysis bullosa, in whom non-healing wounds occur after minor hand injuries which lead to rapid adhesions and devastating contractures.

Keywords:

albumin, nanofibers, wound dressing, biocompatibility, bioresorption

Affiliations:
Noszczyk B.H.-Medical University of Warsaw (PL)
Kowalczyk T.-IPPT PAN
Łyżniak M.-Central Clinical Hospital of the MSWiA (PL)
Zembrzycki K.-IPPT PAN
Mikułowski G.-IPPT PAN
Wysocki J.-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (PL)
Kawiak J.-Nałęcz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences (PL)
Pojda Z.-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (PL)
4.Nakielski P., Kowalczyk T., Zembrzycki K., Kowalewski T.A., Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue, Journal of Biomedical Materials Research Part B: Applied Biomaterials, ISSN: 1552-4973, DOI: 10.1002/jbm.b.33197, Vol.103B, No.2, pp.282-291, 2015
Abstract:

Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing.

Keywords:

neural therapy, brain phantom, drug delivery, laser light sheet, computational modeling, nanofibers

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Zembrzycki K.-IPPT PAN
Kowalewski T.A.-IPPT PAN
5.Pokrywczyńska M., Jundziłł A., Adamowicz J., Kowalczyk T., Warda K., Rasmus M., Buchholz Ł., Krzyżanowska S., Nakielski P., Chmielewski T., Bodnar M., Marszałek A., Dębski R., Frontczak-Baniewicz M.M., Mikułowski G., Nowacki M., Kowalewski T.A., Drewa T., Is the Poly (L- Lactide- Co– Caprolactone) Nanofibrous Membrane Suitable for Urinary Bladder Regeneration?, PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0105295, Vol.9, No.8, pp.105295-1-12, 2014
Abstract:

The purpose of this study was to compare: a new five-layered poly (L–lactide–co–caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L–lactide–co–caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×106 cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×106ADSCs; (II) SIS+ 3×106ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L–lactide–co–caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold.

Keywords:

urinary bladder regeneration, electrospinning

Affiliations:
Pokrywczyńska M.-other affiliation
Jundziłł A.-other affiliation
Bodnar M.-Nicolaus Copernicus University (PL)
Marszałek A.-Nicolaus Copernicus University (PL)
Dębski R.-Nicolaus Copernicus University (PL)
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Mikułowski G.-IPPT PAN
Nowacki M.-other affiliation
Kowalewski T.A.-IPPT PAN
Drewa T.-Nicolaus Copernicus University (PL)
Adamowicz J.-Nicolaus Copernicus University (PL)
Kowalczyk T.-IPPT PAN
Warda K.-other affiliation
Rasmus M.-Nicolaus Copernicus University (PL)
Buchholz Ł.-Nicolaus Copernicus University (PL)
Krzyżanowska S.-other affiliation
Nakielski P.-IPPT PAN
Chmielewski T.-other affiliation
6.Kloskowski T., Jundziłł A., Kowalczyk T., Nowacki M., Bodnar M., Marszałek A., Pokrywczyńska M., Frontczak-Baniewicz M.M., Kowalewski T.A., Chłosta P., Drewa T., Ureter Regeneration–The Proper Scaffold Has to Be Defined, PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0106023, Vol.9, No.8, pp.106023-1-13, 2014
Abstract:

The aim of this study was to compare two different acellular scaffolds: natural and synthetic, for urinary conduit construction and ureter segment reconstruction. Acellular aortic arch (AAM) and poly(L-lactide-co-caprolactone) (PLCL) were used in 24 rats for ureter reconstruction in both tested groups. Follow-up period was 4 weeks. Intravenous pyelography, histological and immunohistochemical analysis were performed. All animals survived surgical procedures. Patent uretero-conduit junction was observed only in one case using PLCL. In case of ureter segment reconstruction ureters were patent in one case using AAM and in four cases using PLCL scaffolds. Regeneration of urothelium layer and focal regeneration of smooth muscle layer was observed on both tested scaffolds. Obtained results indicates that synthetic acellular PLCL scaffolds showed better properties for ureter reconstruction than naturally derived acellular aortic arch.

Keywords:

Ureter, Muscle regeneration, Kidneys, Collagens, Urine, Surgical and invasive medical procedures, Smooth muscles, Inflammation

Affiliations:
Kloskowski T.-other affiliation
Jundziłł A.-other affiliation
Drewa T.-Nicolaus Copernicus University (PL)
Kowalczyk T.-IPPT PAN
Nowacki M.-other affiliation
Bodnar M.-Nicolaus Copernicus University (PL)
Marszałek A.-Nicolaus Copernicus University (PL)
Pokrywczyńska M.-other affiliation
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Kowalewski T.A.-IPPT PAN
Chłosta P.-Jagiellonian University (PL)
7.Gomez-Sanchez C., Kowalczyk T., Ruiz De Eguino G., Lopez-Arraiza A., Infante A., Rodriguez C.I., Kowalewski T.A., Sarrionandia M., Aurrekoetxea J., Electrospinning of poly(lactic acid)/polyhedral oligomeric silsesquioxane nanocomposites and their potential in chondrogenic tissue regeneration, JOURNAL OF BIOMATERIALS SCIENCE, POLYMER EDITION, ISSN: 0920-5063, DOI: 10.1080/09205063.2014.910151, Vol.25, No.8, pp.802-825, 2014
Abstract:

The study was conducted to evaluate the cytocompatibility and hydrolytic degradability of the new poly(lactic acid)/polyethylene glycol-polyhedral oligomeric silsesquioxane (peg-POSS/PLLA) nanocomposite as potential material for cartilage regeneration. PLLA scaffolds containing 0 to 5% of peg-POSS were fabricated by electrospinning. Human mesenchymal stem cells (hMSC’s) were cultured in vitro to evaluate the cytocompatibility of the new nanocomposite material. Hydrolytic degradation studies were also carried out to analyze the mass loss rate of the nanocomposites through time. The addition of the peg-POSS to the PLLA did not affect the processability of the nanocomposite by electrospinning. It was also observed that peg-POSS did not show any relevant change in fibers morphology, concluding that it was well dispersed. However, addition of peg-POSS caused noticeable decrease in mean fiber diameter, which made the specific surface area of the scaffold to rise. hMSC’s were able to attach, to proliferate, and to differentiate into chondrocytes in a similar way onto the different types of electrospun peg-POSS/PLLA and pure PLLA scaffolds, showing that the peg-POSS as nano-additive does not exhibit any cytotoxicity. The hydrolytic degradation rate of the material was lower when peg-POSS was added, showing a higher durability of the nanocomposites through time. Results demonstrate that the addition of peg-POSS to the PLLA scaffolds does not affect its cytocompatibility to obtain hyaline cartilage from hMSC’s.

Keywords:

PLLA, peg-POSS, nanocomposite, electrospinning, chondrocyte, stem cells, scaffold, cartilage repair, hydrolytic degradation

Affiliations:
Gomez-Sanchez C.-Mondragon Unibertsitatea (ES)
Kowalczyk T.-IPPT PAN
Ruiz De Eguino G.-Hospital Universitario Cruces (ES)
Lopez-Arraiza A.-University of the Basque Country (ES)
Infante A.-Hospital Universitario Cruces (ES)
Rodriguez C.I.-Hospital Universitario Cruces (ES)
Kowalewski T.A.-IPPT PAN
Sarrionandia M.-Mondragon Unibertsitatea (ES)
Aurrekoetxea J.-Mondragon Unibertsitatea (ES)
8.Sulejczak D., Andrychowski J., Kowalczyk T., Nakielski P., Frontczak-Baniewicz M.M., Kowalewski T.A., Electrospun nanofiber mat as a protector against the consequences of brain injury, FOLIA NEUROPATHOLOGICA, ISSN: 1641-4640, DOI: 10.5114/fn.2014.41744, Vol.52, No.1, pp.56-69, 2014
Abstract:

Traumatic/surgical brain injury can initiate a cascade of pathological changes that result, in the long run, in severe damage of brain parenchyma and encephalopathy. Excessive scarring can also interfere with brain function and the glial scar formed may hamper the restoration of damaged brain neural pathways. In this preliminary study we aimed to investigate the effect of dressing with an L-lactide-caprolactone copolymer nanofiber net on brain wound healing and the fate of the formed glial scar. Our rat model of surgical brain injury (SBI) of the fronto-temporal region of the sensorimotor cortex imitates well the respective human neurosurgery situation. Brains derived from SBI rats with net-undressed wound showed massive neurodegeneration, entry of systemic inflammatory cells into the brain parenchyma and the astrogliosis due to massive glial scar formation. Dressing of the wound with the nanofiber net delayed and reduced the destructive phenomena. We observed also a reduction in the scar thickness. The observed modification of local inflammation and cicatrization suggest that nanofiber nets could be useful in human neurosurgery.

Keywords:

brain injury, L-lactide-caprolactone copolymer nanofiber net, glial scar, neurodegeneration

Affiliations:
Sulejczak D.-other affiliation
Andrychowski J.-Medical University of Warsaw (PL)
Kowalczyk T.-IPPT PAN
Nakielski P.-IPPT PAN
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Kowalewski T.A.-IPPT PAN
9.Rafałowska J., Sulejczak D., Chrapusta S.J., Gadamski R., Taraszewska A., Nakielski P., Kowalczyk T., Dziewulska D., Non-woven nanofiber mats – a new perspective for experimental studies of the central nervous system?, FOLIA NEUROPATHOLOGICA, ISSN: 1641-4640, DOI: 10.5114/fn.2014.47841, Vol.52, No.4, pp.407-416, 2014
Abstract:

(Sub)chronic local drug application is clearly superior to systemic administration, but may be associated with substantial obstacles, particularly regarding the applications to highly sensitive central nervous system (CNS) structures that are shielded from the outer environment by the blood-brain barrier. Violation of the integrity of the barrier and CNS tissues by a permanently implanted probe or cannula meant for prolonged administration of drugs into specific CNS structures can be a severe confounding factor because of the resulting inflammatory reactions. In this study, we tested the utility of a novel way for (sub)chronic local delivery of highly active (i.e., used in very low amounts) drugs to the rat spinal cord employing a non-woven nanofiber mat dressing. To this end, we compared the morphology and motoneuron ( + ) counts in spinal cord cervical and lumbar segments between rats with glutamate-loaded nanofiber mats applied to the lumbar enlargement and rats with analogical implants carrying no glutamate. Half of the rats with glutamate-loaded implants were given daily valproate treatment to test its potential for counteracting the detrimental effects of glutamate excess. The mats were prepared in-house by electrospinning of an emulsion made of a solution of the biocompatible and biodegradable poly(L-lactide-co-caprolactone) polymer in a mixture of organic solvents, an aqueous phase with or without monosodium glutamate, and sodium dodecyl sulfate as an emulsifier; the final glutamate content was 1.4 µg/mg of the mat. Three weeks after mat implantation there was no inflammation or considerable damage of the spinal cord motoneuron population in the rats with the subarachnoid dressing of a glutamate-free mat, whereas the spinal cords of the rats with glutamate-loaded nanofiber mats showed clear symptoms of excitotoxic damage and a substantial increase in dying/damaged motoneuron numbers in both segments studied. The rats given systemic valproate treatment showed significantly lower percentages of damaged/dying motoneurons in their lumbar enlargements. These results demonstrate the capacity of nanofiber mats for generation of neurotoxic glutamate in the rat CNS. However, the tested nanofiber mats need further improvements aimed at extending the period of effective drug release and rendering the release more steady.

Keywords:

CNS injury, electrospinning, excitotoxicity, glutamate, motoneuron, nanofibers, neurodegeneration, spinal cord, valproate

Affiliations:
Rafałowska J.-other affiliation
Sulejczak D.-other affiliation
Chrapusta S.J.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Gadamski R.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Taraszewska A.-other affiliation
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Dziewulska D.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
10.Kloskowski T., Kowalczyk T., Nowacki M., Drewa T., Tissue engineering and ureter regeneration: Is it possible?, INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, ISSN: 0391-3988, DOI: 10.5301/ijao.5000130, Vol.36, No.6, pp.392-405, 2013
Abstract:

Large ureter damages are difficult to reconstruct. Current techniques are complicated, difficult to perform, and often associated with failures. The ureter has never been regenerated thus far. Therefore the use of tissue engineering techniques for ureter reconstruction and regeneration seems to be a promising way to resolve these problems. For proper ureter regeneration the following problems must be considered: the physiological aspects of the tissue, the type and shape of the scaffold, the type of cells, and the specific environment (urine). 
This review presents tissue engineering achievements in the field of ureter regeneration focusing on the scaffold, the cells, and ureter healing.

Affiliations:
Kloskowski T.-other affiliation
Kowalczyk T.-IPPT PAN
Nowacki M.-other affiliation
Drewa T.-Nicolaus Copernicus University (PL)
11.Andrychowski J., Frontczak-Baniewicz M.M., Sulejczak D., Kowalczyk T., Chmielewski T., Czernicki Z., Kowalewski T.A., Nanofiber nets in prevention of cicatrisation in spinal procedures. Experimental study, FOLIA NEUROPATHOLOGICA, ISSN: 1641-4640, DOI: 10.5114/fn.2013.35958, Vol.51, No.2, pp.147-157, 2013
Abstract:

Excessive cicatrisation or epidural fibrosis in the operative field is an inappropriate event occasionally occurring after neurosurgical procedures (i.e., spine procedures and craniotomies). This excessive process may disturb the postopera­tive course and render reoperations more difficult and risky. The literature describes this phenomenon as accompanying up to 20% of neurosurgical procedures. The scar tissue that forms postoperatively adheres to the dura mater, penetrates into the spinal canal and can cause narrowing symptoms, neurological deficits and pain. The incidence and spread of this excessive scar or epidural fibrosis can be prevented through the modification of the surgical technique by incorporating endoscopic or microscopic access to minimize the operative field and the use of isolating substances (autogenous or heterogeneous) administered intraoperatively.

The aim of this experimental study was to morphologically assess the cicatrisation process, adhesion and to prevent excessive scar formation with the local use of membranes manufactured by an electrospinning process (nanotechnology). We also investigated whether the biodegradable nanofibrous net triggers or modifies the immunological response or the local inflammatory process.

Micro-nanofibrous membranes were produced by the electrospinning process. A biodegradable, medically certified copolymer poly(L-lactide-co-caprolactone) (PLCL) was used as the electrospun material.

An experimental rat model was used in this study. Experimental and control groups were formed with specified follow-up times of 4, 14 and 30 days. During the operation, a two-level laminectomy in the thoracic segment was performed. The operative field was divided into two regions. Isolating material was used on the dura mater and surface of the spinal cord in the area where the laminectomy was performed. The material was analysed with the use of light and electron microscopy.

Local cicatrisation can be modified using nanomaterials. Scar formation and epidural fibrosis can be limited and modi­fied locally. No local inflammation process was observed.

Initial observations indicate the potential for the effective use of materials obtained in the electrospinning process to prevent cicatrisation.

Keywords:

neurosurgery, cicatrisation, epidural fibrosis, copolymer, poly(L-lactide-co-caprolactone), nanofibrous net, rat model

Affiliations:
Andrychowski J.-Medical University of Warsaw (PL)
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Sulejczak D.-other affiliation
Kowalczyk T.-IPPT PAN
Chmielewski T.-other affiliation
Czernicki Z.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Kowalewski T.A.-IPPT PAN
12.Adamowicz J., Kowalczyk T., Drewa T., Tissue engineering of urinary bladder – current state of art and future perspectives, Central European Journal of Urology, ISSN: 2080-4806, DOI: 10.5173/ceju.2013.02.art23, Vol.66, pp.202-206, 2013
Abstract:

Introduction.
Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary bladder based on tissue engineering methods. Materials and methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells.

Results.
Numerous studies to develop a substitute for the native urinary bladder wall using the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application.

Conclusions.
Before tissue engineering techniques could be recognize as effective and safe for patients, more research studies performed on large animal models and with long follow–up are needed to carry on in the future.

Keywords:

stem cells, bladder regeneration, tissue engineering

Affiliations:
Adamowicz J.-Nicolaus Copernicus University (PL)
Kowalczyk T.-IPPT PAN
Drewa T.-Nicolaus Copernicus University (PL)
13.Nakielski P., Kowalczyk T., Kowalewski T.A., Drug delivery system based on polymer nano-fibers, IPPT REPORTS, ISSN: 2299-3657, Vol.4b, pp.1-6, 2013
Abstract:

This work presents our attempts to characterize release of two model drugs from electrospun polymer nanofibers. Such drug delivery system offers great potential for applications in medicine especially as neurosurgery protective membranes. Proper delivery of drugs requires precise control of the drug diffusion process during the release for days or even weeks. Lipophilic model drug Rhodamine B and hydrophilic Bovine Serum Albumin conjugated with Fluoresceine (BSA - FITC) were embedded in electrospun poly(L -lactide-co -ε-caprolactone) (PLC) nanofibers. Release of Rhodamine B showed saturation in cumulative release profile at 60% and 86% for 1.5% and 3% wt. initial drug content, respectively. Nanofibers electrospun from emulsion released almost entire drug encapsulated in water vesicles inside the nanofibers. Possible location of vesicles close to the surface of the nanofibers exposed them for surrounding fluid and caused leaching of the drug. In this case encapsulation of drug in emulsion prevented the initial burst release.Dependence of a drug release and composition of nanofiber is essential for production of drug delivery systems. Mathematical model constructed with this data allows to avoid tedious experimental work. This research was supported by Ministry of Science and Higher Education, National Centre for Research and Development Project grant no. R13008110. The first author has been supported with a scholarship from the European Social Fund, Human Capital Operational Programme.

Keywords:

nanofibres, drug delivery, vesicles

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
14.Blim A., Kowalczyk T., Dynamic lattice liquid (DLL) model in computer simulation of the structure and dynamics of polymer condensed systems, E-POLYMERS, ISSN: 1618-7229, Vol.2012, No.079, pp.1-11, 2012
15.Nowacki M., Jundziłł A., Bieniek M., Kowalczyk T., Kloskowski T., Drewa T., Nowoczesne biomateriały jako opatrunki hemostatyczne w chirurgii oszczędzającej miąższ nerki-model zwierzęcy. Doniesienie wstępne., POLIMERY W MEDYCYNIE, ISSN: 0370-0747, Vol.42, No.1, pp.35-43, 2012
16.Kowalewski T.A., Kowalczyk T., Frontczak-Baniewicz M.M., Gołąbek-Sulejczak D.A., Andrychowski J., Nanofibres for medical applications at Biocentrum Ochota, Annual Report - Polish Academy of Sciences, ISSN: 1640-3754, pp.62-65, 2011
Abstract:

Electrospun nonwovens have recently been successfully applied as a dressing material in spinal neurosurgery. Scarring is known to be one of the major post-operative complications for neurosurgery. If it occurs, it may trap a nerve, so that when a patient moves the nerve becomes stretched, causing nerve damage, pain, and internal scarring of the nerve. This causes subsequent complications related to ingrowths of connective tissue onto the spinal canal. The formation of an astroglial scar is another serious postoperative complication of brain neuro-surgery. The use of bio-absorbable isolative materials as anti-liaison protection and as possible carriers for neuroprotective drug delivery is expected to help in solving such problems. The nanostructured material acts as an anti-bacterial and anti-liaison barrier while enabling transport of oxygen, nutrients, and metabolites, facilitating the healing process of the surgical wound.

Keywords:

Nanofibres for neurosurgery, protection of scar formation

Affiliations:
Kowalewski T.A.-IPPT PAN
Kowalczyk T.-IPPT PAN
Frontczak-Baniewicz M.M.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Gołąbek-Sulejczak D.A.-other affiliation
Andrychowski J.-Medical University of Warsaw (PL)
17.Bretcanu O., Misra S.K., Yunos D.M., Boccaccini A.R., Roy I., Kowalczyk T., Błoński S., Kowalewski T.A., Electrospun nanofibrous biodegradable polyester coatings on Bioglass®-based glass-ceramics for tissue engineering, MATERIALS CHEMISTRY AND PHYSICS, ISSN: 0254-0584, DOI: 10.1016/j.matchemphys.2009.08.011, Vol.118, pp.420-426, 2009
Abstract:

Biodegradable polymeric nanofibrous coatings were obtained by electrospinning different polymers onto sintered 45S5 Bioglass®-based glass-ceramic pellets. The investigated polymers were poly(3-hydroxybutyrate) (P3HB), poly(3-hydroxybutyrate-co-hydroxyvalerate) (PHBV) and a composite of poly(caprolactone) (PCL) and poly(ethylene oxide) (PEO) (PCL–PEO). The fibrous coatings morphology was evaluated by optical microscopy and scanning electron microscopy. The electrospinning process parameters were optimised to obtain reproducible coatings formed by a thin web of polymer nanofibres. In-vitro studies in simulated body fluid (SBF) were performed to investigate the bioactivity and mineralisation of the substrates by inducing the formation of hydroxyapatite (HA) on the nanofiber-coated pellets. HA crystals were detected on all samples after 7 days of immersion in SBF, however the morphology of the HA layer depended on the characteristic fibre diameter, which in turn was a function of the specific polymer-solvent system used. The bioactive and resorbable nanofibrous coatings can be used to tailor the surface topography of bioactive glass-ceramics for applications in tissue engineering scaffolds.

Keywords:

Electrospinning, Nanofibers, Bioglass®, Polyhydroxyalkanoates, Tissue engineering

Affiliations:
Bretcanu O.-other affiliation
Misra S.K.-other affiliation
Yunos D.M.-other affiliation
Boccaccini A.R.-other affiliation
Roy I.-other affiliation
Kowalczyk T.-IPPT PAN
Błoński S.-IPPT PAN
Kowalewski T.A.-IPPT PAN
18.Fryczkowski R., Kowalczyk T., Nanofibres from polyaniline/polyhydroxybutyrate blends, SYNTHETIC METALS, ISSN: 0379-6779, Vol.159, No.21-22, pp.2266-2268, 2009
19.Kowalczyk T., Nowicka A., Elbaum D., Kowalewski T.A., Electrospinning of bovine serum albumin. Optimization and the use for production of biosensors, BIOMACROMOLECULES, ISSN: 1525-7797, DOI: 10.1021/bm800421s, Vol.9, No.7, pp.2087-2090, 2008
Abstract:

Electrospinning of the globular protein, bovine serum albumin (BSA), was optimized to obtain proteinous fibers suitable asbiosensors. It was shown that the as-spun protein preserves its native form, whereas solubility of the cross-linked in the ambient conditions BSA nanofibers evidently decreases. Insoluble BSA fibers can be easily modified to be used as two-dimensional biosensors. Here, we show the micro pH sensor obtained from the BSA fiber stained with a fluorescein derivative (FITC).

Keywords:

Electrospinning BSA, pH sensor

Affiliations:
Kowalczyk T.-IPPT PAN
Nowicka A.-IPPT PAN
Elbaum D.-other affiliation
Kowalewski T.A.-IPPT PAN

List of chapters in recent monographs
1.
16
Gambin B., Lekszycki T., Kowalczyk T., Kowalewski T.A., Ziółkowski A., Pieczyska E.A., Stupkiewicz S., Scenariusze rozwoju technologii nowoczesnych materiałów metalicznych, ceramicznych i kompozytowych, rozdział: Biomateriały. Rola i strategia badawcza IPPT PAN w powstaniu nowoczesnych technologii materiałów współpracujących z ludzkimi tkankami, Wydawnictwo Naukowe Instytutu Technologii Eksploatacji PIB, 1, pp.181-222, 2010
2.
158
Kowalewski T.A., Barral S., Kowalczyk T., IUTAM Symposium on modelling nanomaterials and nanosystems, IUTAM Bookseries, rozdział: Modeling electrospinning of nanofibers, Springer, Pyrz R., Rauhe J.C. (Eds.), 13, pp.279-292, 2009

Conference papers
1.Nakielski P., Kowalczyk T., Kowalewski T.A., Modeling Drug Release from Materials Based on Electrospun Nanofibers, COMSOL 2013, COMSOL Conference, 2013-10-23/10-25, Rotterdam (NL), pp.1-6, 2013
Abstract:

Comprehensive studies of drug transport in nanofibres based mats have been performed to predict drug release kinetics. The paper presents our approach to analyze the impact of fibers arrangement, one of the parameters varied in our parallel experimental studies. Drug encapsulation in submicron fibers and subsequent controlled release of drugs is a tedious task due to the large number of process and material parameters involved. In the numerical study we constructed a 3D finite element geometry representing nanofibrous cubic element. COMSOL Multiphysics has been used to assess the impact of the various purposed arrangements of fibers within the mat. Drug release from nanofibers was modeled by adsorption -desorption and diffusion equation, where drug diffusion coefficient in the fluid between the fibers was altered depending on porosity of the material. Our study shows that for the same material porosity drug release from the matrix of regularly oriented fibers is slower than from randomly oriented, isotropic nanofibrous material. Also by decreasing distance between the fibers drug transport rate is reduced.

Keywords:

Nanofibres, finite elements, drug release modelling

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
2.Kowalewski T.A., Barral S., Kowalczyk T., Modeling Electrospinning of Nanofibers, in Modelling Nanomaterials and Nanosystems, IUTAM Symposium, 2009-05-19/05-22, Aalborg (DK), Vol.13, pp.279-292, 2009
Abstract:

A fast discrete model for the simulations of thin charged jets produced during the electrospinning process is derived, based on an efficient implementation of the boundary element method for the computation of electrostatic interactions of the jet with itself and with the electrodes. Short-range electrostatic forces are evaluated with slender-body analytical approximations, whereas a hierarchical force evaluation algorithm is used for long-range interactions. Qualitative comparisons with experiments is discussed.

Keywords:

modelling electrospinning, electrostatic interactions, BEM

Affiliations:
Kowalewski T.A.-IPPT PAN
Barral S.-IPPT PAN
Kowalczyk T.-IPPT PAN

Conference abstracts
1.Kowalczyk T., Cwiek K., Urbanek O., Kloskowski T., Pokrywczyńska M., Jundziłł A., Adamowicz J., Zabost E., Noszczyk B., Drewa T., Electrospun micro and nanofibers applied for animal models in urology and wound dressing. Potential applications in cancer treatment, 2nd INTERNATIONAL CONFERENCE ON BIO-BASED POLYMERS AND COMPOSITES, 2014-08-24/08-28, Visegrad (HU), pp.24, 2015
Abstract:

We used the principles of electrospinning to produce materials for applications in regenerative medicine of urinary bladder wall, ureter, wound dressing and potential applications in cancer therapy. Our research is based on biodegradable polymers produced by ring-opening polymerization. Scaffolds of poly(L-lactide-co-caprolactone) (PLCL) gradually degrade leaving no artificial material behind to be replaced by natural extracellular collagen matrix. We formed flat membranes of micro- and nanofibers to carry out regeneration of urinary bladder wall as animal model of cancer treatment. Grafts were tested for biocompatibility and aimed for guided cell growth, yet we were unsuccessful in mechanical compliance of nanomaterial and reconstructed tissue. We tested tubular scaffolds made of nanofibers aimed for ureter tissue engineering. We found stem cells seeding unnecessary. The results of nanomaterial implantation on animal model were better than for collagen matrices. Animal model was also tested for use of nanofibers of human serum albumin as wound dressing. The native structure of the protein was retained to maintain its anti-adhesive properties, despite poor mechanical characteristics. Nanomaterial caused no inflammation and was resorbed during 16 days. Last application of presented materials was targeted drug delivery system made of PLCL nanofibers. Release of anticancer drug complexed with nanoparticles is to be triggered by tumor cells. Such nanomaterial is potential drug delivery system. Acknowledgements: The authors wishes to thank for the cooperation: T. Chmielewski, P. Nakielski, K. Zembrzycki, G. Mikulowski and prof. T. A. Kowalewski from IPPT PAN. The project was partially supported by the National Centre for Research and Development. Grant No. STRATEGMED1/235368/8/NCBR/2014.

Keywords:

electrospinning, nanofibers, regenerative medicine, wound dressing, urology, biodegradable polymers, animal model.

Affiliations:
Kowalczyk T.-IPPT PAN
Cwiek K.-other affiliation
Urbanek O.-IPPT PAN
Kloskowski T.-other affiliation
Pokrywczyńska M.-other affiliation
Jundziłł A.-other affiliation
Adamowicz J.-Nicolaus Copernicus University (PL)
Zabost E.-University of Warsaw (PL)
Noszczyk B.-Medical University of Warsaw (PL)
Drewa T.-Nicolaus Copernicus University (PL)
2.Dziewulska D., Gadamski R., Taraszewska A., Chrapusta S., Sulejczak D., Kowalczyk T., Chrzanowska A., Ogonowska W., Wojda R., Wąsowska L., Rafałowska J., Nanofibers mats - a new perspective for experimental studies of the nervous system, Brain Pathology, ISSN: 1015-6305, DOI: 10.1111/bpa.12184, Vol.24, No.S1, pp.57, 2014
Abstract:

Introduction:
Introduction of nanotechnology into medicine has provided new therapeutic options. It has been demonstrated that implantation of nanofiber mats after nervous system injury allowed to diminish scar size and infl ammatory reaction. It is also possible that, due to their ability to release active factors, nanofiber mats may replace intracerebral probes. To assess potential usefulness of nanofiber mats in releasing active substances we implanted them into the spinal cord subarachnoid space in adult Wistar rats.

Material and Method:
The experimental animals were divided into four groups: group 1 – rats with implanted nanofiber mats, group 2 – rats with implanted nanofiber mats releasing glutamate, group 3 – rats with nanofiber mats releasing glutamate and treated orally by sodium valproate, and group 4 – control animals without nanofiber mats. The animals were killed 21 days after the mats implantation. Then, histopathological, immunohistochemical and ultrastructural evaluation of the spinal cords was performed.

Results:
Morphological assessment revealed that implantation of nanofi ber mats caused neither spinal cord damage nor inflammation (group 1). Also nanofi ber mats releasing glutamate did not produce inflammatory reaction (group 2 and 3) although in group 2 morphological changes indicating toxic influence of glutamate were observed. These changes were less severe in group 3.

Conclusions:
(1) Nanofi ber mats are biocompatible and can be useful in long-term animal experiments. (2) Nanofi ber mats are able to release glutamate into the subarachnoid space. (3) Sodium valproate has a protective influence against glutamate toxicity.

Keywords:

electrospinning, nanofibers, drug delivery, neurology, sodium glutamate, animal model.

Affiliations:
Dziewulska D.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Gadamski R.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Rafałowska J.-other affiliation
Taraszewska A.-other affiliation
Chrapusta S.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Sulejczak D.-other affiliation
Kowalczyk T.-IPPT PAN
Chrzanowska A.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Ogonowska W.-other affiliation
Wojda R.-Mossakowski Medical Research Centre, Polish Academy of Sciences (PL)
Wąsowska L.-other affiliation
3.Nakielski P., Kowalczyk T., Kowalewski T.A., Modelowanie procesu uwalniania leków z materiałów opartych na nanowłóknach, 53 Sympozjon „Modelowanie w mechanice”, 2014-02-22/02-26, Ustroń (PL), pp.112-113, 2014
Keywords:

nanomaty, modelowanie uwalniania leku

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
4.Nakielski P., Kowalczyk T., Kowalewski T.A., Evaluation of drug release from electrospun nanofibers by modification of material morphology, EYEC, 3rd European Young Engineers Conference, 2014-04-29/04-30, Warszawa (PL), pp.220-221, 2014
Keywords:

drug delivery, electrospinning, mathematical modeling, nanofibres

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
5.Nakielski P., Kowalczyk T., Kowalewski T.A., Zastosowanie materiałów z nanowłókien w inżynierii regeneracyjnej, I Konferencja Młodych Naukowców „Biotechnologia w produkcji zwierzęcej” SGGW, 2014-04-24/04-25, Warszawa (PL), pp.25, 2014
Keywords:

elektroprzędzenie, nanowłókna, uwalnianie leków, TBI

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
6.Nakielski P., Kowalczyk T., Kowalewski T.A., Modeling drug delivery from nanofibers to brain tissue, XXI FMC, XXI Fluid Mechanics Conference, 2014-06-15/06-18, Kraków (PL), pp.24, 2014
Keywords:

brain, drug delivery, nanofibres, mathematical modelling

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
7.Nakielski P., Kowalczyk T., Kowalewski T.A., Experimental study of drug release system based on electrospun nanofibres, ICTAM XXIII, 23rd International Congress of Theoretical and Applied Mechanics, 2012-08-19/08-24, Beijing (CN), pp.CD-ROM FS10-007, 2012
Abstract:

The paper contains our attempts to estimate diffusion parameters of nanofibers actually applied as protective mats for neurosurgery. Measurements of concentration profiles of fluorophore released from stained nanofibres are performed. The two release systems are investigated: solid nanofibres and core-shell nanofibres with targeted drug simulator encapsulated inside nanofibres. The gathered information allows us to estimate parameters necessary for controlling drug release profiles.

Keywords:

Nanofibers, Electrospinning, Drug Delivery Systems

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
8.Nakielski P., Kowalczyk T., Kowalewski T.A., Experimental study of drug release system based on electrospun nanofibers, III National Conference of Nano and Micromechanics, 2012-07-04/07-06, Warszawa (PL), pp.149-150, 2012
Abstract:

Nanofibers produced by electrospinning of biologically active substances became attractive material for encapsulating living cells, bacteria, and drugs for targeted therapy. Here, we aim to use nanofiber matrices as neurosurgery protective membranes and drug carriers. Proper administration of drugs requires precise control of the diffusion process during the time of release of days or even weeks. Construction of such system is a tedious experimental task. To avoid hundreds of tests it is aimed to build a numerical model including essential information about composition, process conditions, and fibers geometry necessary to construct suitable polymer matrices for dedicated drug delivery systems.

Keywords:

drug delivery, electrospinning, nanofibers

Affiliations:
Nakielski P.-IPPT PAN
Kowalczyk T.-IPPT PAN
Kowalewski T.A.-IPPT PAN
9.Kowalczyk T., Nakielski P., Kowalewski T.A., Application of nanofibers as Drug Delivery Systems, III National Conference of Nano and Micromechanics, 2012-07-04/07-06, Warszawa (PL), pp.39-40, 2012
Abstract:

This paper describes the results of our preliminary studies on Drug Delivery Systems. Two distinct types of drugs are being investigated: lipophylic (soluble in organic solvents) and hydrophylic (soluble in water). Direct measurements of drugs and dye release from nanofibers were done for application in an animat model - rat.

Keywords:

Electrospinnig, Nanofibers, Drug Delivery Systems

Affiliations:
Kowalczyk T.-IPPT PAN
Nakielski P.-IPPT PAN
Kowalewski T.A.-IPPT PAN

Patents
Numer/data zgłoszenia patentowego
Ogłoszenie o zgłoszeniu patentowym
Twórca / twórcy
Tytuł
Kraj i Nazwa uprawnionego z patentu
Numer patentu
Ogłoszenie o udzieleniu patentu
pdf
411421
2015-02-27
BUP 18/2016
2016-08-29
Kowalczyk T., Noszczyk B.H.
Sposób otrzymywania elektroprzędzonych materiałów zawierających natywne białka oraz ich zastosowanie, zwłaszcza jako materiałów opatrunkowych i systemów uwalniania leków
PL, Instytut Podstawowych Problemów Techniki PAN, Centrum Medyczne Kształcenia Podyplomowego
-
-
-
404667
2013-07-12
BUP 2/15
2015-01-19
Andrychowski J., Frontczak-Baniewicz M.M., Czernicki Z.M., Gołąbek-Sulejczak D.A., Kowalczyk T., Kowalewski T.A., Nakielski P.
Zastosowanie siatki izolacyjnej z nanowłókien polimerowych wykonanej w technologii elektroprzędzenia do wytwarzania opatrunków neuroprotekcyjnych do stosowania w zapobieganiu pourazowym zmianom w mózgu
PL, Warszawski Uniwersytet Medyczny, Instytut Medycyny Doświadczalnej i Klinicznej PAN, Instytut Podstawowych Problemów Techniki PAN
225858
WUP 05/17
2017-05-31
395899
2011-08-08
BUP 4/2013
2013-02-18
Andrychowski J., Frontczak-Baniewicz M.M., Czernicki Z.M., Gołąbek-Sulejczak D.A., Kowalczyk T., Kowalewski T.A.
Zastosowanie polimerowej siatki izolacyjnej wytwarzanej z nanowłókien polimerowych do zapobiegania bliznowaceniu po zabiegu neurochirurgicznym
PL, Warszawski Uniwersytet Medyczny, Instytut Medycyny Doświadczalnej i Klinicznej PAN, Instytut Podstawowych Problemów Techniki PAN
226479
WUP 07/2017
2017-07-31
390140
2010-01-07
BUP 15/11
2011-07-18
Kowalewski T.A., Lamparska D., Zembrzycki K., Kowalczyk T.,
Sposób wytwarzania mat z nanowłókien
PL, Instytut Podstawowych Problemów Techniki PAN
222733
WUP 08/16
2016-08-31