Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Nově navržený hybridní biodegradabilní nanokompozitní porézní implantát (HBNPI) modifikovaný biogenním polyfosfátem (bio-polyP) představuje velmi dobrou možnost jak vytvořit kostní fúzi. Zvláště efektivní využití se nabízí v páteřní problematice, kde při jejím poranění či degenerativním postižení je často využívána metoda tzv. intervertebrální dézy. Námi navržený resorbovatelný HBNPI složený z vnějšího tvrdého keramického prstence a vnitřní měkké kolagen/nanohydroxyapatitové pěny v kombinaci s bio-polyP kopíruje osteokonduktivní a osteoinduktivní vlastnosti dosud užívaných autologních kostních štěpů. Syntetický HBNPI je připravován laboratorně a tím odpadají komplikace spojené s odběrem autoštěpů, eventuálně i riziko přenosu infektu v případě užití aloštěpu. Tento projekt se zaměřuje na in-vivo testování schopnosti HBNPI vytvořit intevertebrální dézu na zvířecím modelu a provést histologické a ex-vivo biomechanické porovnání s dosud užívanými autoštěpy. Výsledky budou tvořit podklad k vytvoření nové a bezpečnější metodiky intervertebrální dézy a umožní následné klinické testování.; Newly designed hybrid biodegradable nanocomposite porous implant (HBNPI) modified with biogenic polyphosphate (bio-polyP) represents a very good opportunity to create bone fusion. Particularly effective utilization seems to be in spinal problems ,where the method of intervertebral fusion is mainly applied in injuries or degenerative spinal diseases. Our designed resorbable HBNPI composed of a hard ceramic outer ring and the inner soft collagen/nanohydroxyapatit foam modified with bio-polyP copy osteoconductive and osteoinductive properties of currently used autologous bone grafts. Synthetic HBNPI is prepared in laboratory manner eliminating both the complications associated with autografts collection and possibly the risk of infection transmission in the case of allografts. This project is focused on in-vivo testing of HBNPI ability to create intervertebral fusion in animal model and compare histology and ex-vivo bimechanics with standard autograft method. Results will create base of new and safer method of intervertebral fusion allowing subsequent clinical testing.
- MeSH
- fúze páteře metody MeSH
- implantace protézy MeSH
- lidé MeSH
- modely u zvířat MeSH
- nanokompozity terapeutické užití MeSH
- páteř chirurgie MeSH
- polyfosfáty terapeutické užití MeSH
- prasata MeSH
- testování materiálů MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- hodnotící studie MeSH
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- ortopedie
- technika lékařská, zdravotnický materiál a protetika
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Many growth factors have been studied as additives accelerating lumbar fusion rates in different animal models. However, their low hydrolytic and thermal stability both in vitro and in vivo limits their workability and use. In the proposed work, a stabilized vasculogenic and prohealing fibroblast growth factor-2 (FGF2-STAB®) exhibiting a functional half-life in vitro at 37 °C more than 20 days was applied for lumbar fusion in combination with a bioresorbable scaffold on porcine models. An experimental animal study was designed to investigate the intervertebral fusion efficiency and safety of a bioresorbable ceramic/biopolymer hybrid implant enriched with FGF2-STAB® in comparison with a tricortical bone autograft used as a gold standard. Twenty-four experimental pigs underwent L2/3 discectomy with implantation of either the tricortical iliac crest bone autograft or the bioresorbable hybrid implant (BHI) followed by lateral intervertebral fixation. The quality of spinal fusion was assessed by micro-computed tomography (micro-CT), biomechanical testing, and histological examination at both 8 and 16 weeks after the surgery. While 8 weeks after implantation, micro-CT analysis demonstrated similar fusion quality in both groups, in contrast, spines with BHI involving inorganic hydroxyapatite and tricalcium phosphate along with organic collagen, oxidized cellulose, and FGF2- STAB® showed a significant increase in a fusion quality in comparison to the autograft group 16 weeks post-surgery (p = 0.023). Biomechanical testing revealed significantly higher stiffness of spines treated with the bioresorbable hybrid implant group compared to the autograft group (p < 0.05). Whilst histomorphological evaluation showed significant progression of new bone formation in the BHI group besides non-union and fibrocartilage tissue formed in the autograft group. Significant osteoinductive effects of BHI based on bioceramics, collagen, oxidized cellulose, and FGF2-STAB® could improve outcomes in spinal fusion surgery and bone tissue regeneration.
- Publikační typ
- časopisecké články MeSH
The structure degradation and strength changes of calcium phosphate scaffolds after long-term exposure to an acidic environment simulating the osteoclastic activity were determined and compared. Sintered calcium phosphate scaffolds with different phase structures were prepared with a similar cellular pore structure and an open porosity of over 80%. Due to microstructural features the biphasic calcium phosphate (BCP) scaffolds had a higher compressive strength of 1.7 MPa compared with the hydroxyapatite (HA) and β-tricalcium phosphate (TCP) scaffolds, which exhibited a similar strength of 1.2 MPa. After exposure to an acidic buffer solution of pH = 5.5, the strength of the HA scaffolds did not change over 14 days. On the other hand, the strength of the TCP scaffolds decreased steeply in the first 2 days and reached a negligible value of 0.09 MPa after 14 days. The strength of the BCP scaffolds showed a steady decrease with a reasonable value of 0.5 MPa after 14 days. The mass loss, phase composition and microstructural changes of the scaffolds during degradation in the acidic environment were investigated and a mechanism of scaffold degradation was proposed. The BCP scaffold showed the best cell response in the in vitro tests. The BCP scaffold structure with the highly soluble phase (α-TCP) embedded in a less soluble matrix (β-TCP/HA) exhibited a controllable degradation with a suitable strength stability and with beneficial biological behavior it represented the preferred calcium phosphate structure for a resorbable bone scaffold.
- MeSH
- buněčná adheze MeSH
- DNA metabolismus MeSH
- fosforečnany vápenaté chemie MeSH
- keramika chemie MeSH
- koncentrace vodíkových iontů MeSH
- kosti a kostní tkáň fyziologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie MeSH
- pevnost v tlaku MeSH
- poréznost MeSH
- tkáňové podpůrné struktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA⁻PEG⁻PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA⁻PEG⁻PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA⁻PEG⁻PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.
- MeSH
- biokompatibilní materiály chemie MeSH
- fosforečnany vápenaté chemie MeSH
- koncentrace vodíkových iontů MeSH
- kostní cementy chemie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mechanické jevy MeSH
- molekulární struktura MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemická syntéza chemie MeSH
- polyglactin 910 chemická syntéza chemie MeSH
- polymerizace MeSH
- reologie MeSH
- testování materiálů MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH