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Article Corrigendum to: Developing a novel resorptive hydroxyapatite-based bone substitute for over-critical size defect reconstruction: physicochemical and biological characterization and proof of concept in segmental rabbit’s ulna reconstruction was published on June 28, 2022 in the journal Biomedical Engineering / Biomedizinische Technik

Background/Aim. The materials used nowadays for bone replacement do not fully meet the requirements for complete regeneration, which is why new ones are being tested. Despite numerous attempts to improve bone tissue regeneration, no fulfilling material has been found yet. This study investigated the influence of poly-lactide-co-glycolide (PLGA) and polyethyleneimine (PEI) as coatings for hydroxyapatite (HAP) bone carriers on bone tissue regenerative potential in rabbits? calvarial defect. Methods. Calvarial defects measuring 6 mm in diameter were made in 19 skeletally mature rabbits. Defects were filled with one of the following materials: PLGA coated HAP (HAP + PLGA), PEI coated HAP (HAP + PEI), and bovine HAP ? Bio-Oss? (positive control). Unfilled defects represented negative control. Histological analysis was performed in order to determine the inflammatory response of the host tissue. The formation of the new bone was evaluated using histomorphometric analysis. All analyses have been conducted in samples obtained 3, 6, and 9 weeks after implantation. Results. Three weeks post-implantation, a trend toward increased healing in the HAP + PLGA group compared to other investigated materials was noticed, with no statistically significant difference between the study groups (p > 0.05). However, after 6 and 9 weeks, significant healing was observed in favor of the HAP coated with PLGA compared to other groups (p, Uvod/Cilj. Materijali koji se u današnje vreme koriste za nadoknadu koštanog tkiva ne dovode do kompletne regeneracije, zbog čega se ispituju novi. Uprkos mnogobrojnim pokušajima da se poboljša regeneracija koštanog tkiva, još uvek nije pronađen materijal koji ispunjava sve kriterijume. Cilj rada bio je da se utvrdi uticaj poli(laktid-ko-glikolida) (PLGA) i polietilenimina (PEI), kao premaza za oblaganje hidroksiapatita (HAP), na regenerativni potencijal koštanog tkiva u defektu kalvarije zeca. Metode. Kod 19 zečeva „zrelog” skeleta načinjeni su defekti kalvarije dijametra 6 mm. Defekti su potom ispunjeni jednim od sledećih materijala: HAP obložen PLGA (HAP + PLGA), HAP obložen PEI (HAP + PEI) i goveđi HAP – Bio-Oss® (pozitivna kontrola). Prazni defekti su predstavljali negativnu kontrolu. Inflamacijska reakcija tkiva domaćina je ispitana histološkom analizom. Formiranje nove kosti je procenjivano histomorfometrijskom analizom. Analizirani su uzorci dobijeni 3, 6 i 9 nedelja nakon implantacije. Rezultati. Tri nedelje nakon implantacije, uočena je tendencija boljeg zarastanja u HAP + PLGA grupi, bez statistički značajne razlike između ispitivanih grupa (p > 0.05). Međutim, 6 i 9 nedelja nakon implantacije, primećeno je značajno formiranje koštanog tkiva u korist HAP + PLGA grupe (p < 0,05). Oblaganje HAP sa PLGA dovelo je do boljeg koštanog zarastanja u poređenju sa HAP+PEI i Bio-Oss®. Zaključak. U pogledu stimulisanja osteogeneze u rekonstruktivnoj hirurgiji kostiju, PLGA je pokazao veći potencijal prekrivanja defekta od PEI.

Razvoj lica, usne i nosne duplje predstavljaju niz međusobno veoma usko povezanih procesa praćenih promenama morfologije zahvaćenih regija. Razviće lica započinje već u 4. nedelji intrauterinog razvoja. Ovaj izuzetno komplikovan proces, se skoro u potpunosti završava do 9. nedelje razvića. Ipak znaci razvoja usne duplje započinju značajno ranije već oko 16. dana embrionalnog razvoja. Već sredinom 3. nedelje u predelu bukofaringealne membrane zapaža se udubljenje koje prethodi stomatodeumu- primitivnoj usnoj duplji. Između 21. i 31. dana u kranijalnom predelu razvija se pet procesusa: gornji frontonazalni, dva bočna maksilarna i dva mandibularna procesusa. Pod stomatodeuma čini bukofaringealna membrana. U početku tzv. primitivno lice se oslanja na perikardno ispupčenje, ali rastom mandibularnih procesusa napred i prema sredini, dolazi do njihovog srastanja, što odvaja stomatodeum od perikardnog ispupčenja. Istovremeno rastu i maksilarni nastavci prema gore, napred i prema sredini. Frontonazalni procesus raste na dole i od njega se razvijaju čelo i nos. Njegov medijalni deo rastom na dole formira globularni procesus od koga nastaju strukture nosa, frenulum gornje usne i primarni palatum. U formiranju primarnog nepca (krajem 6 nedelje) učestvuju maksilarni procesusi koji rastom i spajanjem sa medijalnim delom frontonazalnog nastavka stvaraju osnovu za razvoj obraza i ostalih delova gornje usne. Na ovaj način se odvaja primitivna usna i nosna duplja. Stomatodeum se produbljuje rastom facijalnih nastavaka, da bi se oko 28 dana rupturiranjem bukofaringealne membrane ostvarila komunikacija stomatodeuma sa primitivnim ždrelom. Spajanjem palatinalnih procesusa u srednjoj liniji napred sa primarnim nepcem, a gore sa nosnim septumom, formira se i sekundarno nepce (oko 12 nedelje). Vremenski srastanjem svih nastavaka dolazi do nestajanja epitela na njihovim krajevima, odnosno do urastanja mezenhima na njihovim spojevima. Od mezoderma u predelu tvrdog nepca razviće se kost, a u

The aim of this study was to develop novel hydroxyapatite (HAP)-based bioactive bone replacement materials for segmental osteotomy reconstruction. Customized three-dimensional (3D) bone construct was manufactured from nanohydroxyapatite (nHAP) with poly(lactide-co-glycolide) (PLGA) coating using 3D models derived from the computed tomography (CT) scanning of the rabbit's ulna and gradient 3D printing of the bone substitute mimicking the anatomical shape of the natural bone defect. Engineered construct revealed adequate micro-architectural design for successful bone regeneration having a total porosity of 64% and an average pore size of 256 μm. Radiography and micro-CT analysis depicted new bone apposition through the whole length of the reconstructed ulna with a small area of non-resorbed construct in the central area of defect. Histological analysis revealed new bone formation with both endochondral and endesmal type of ossification. Immunohistochemistry analysis depicted the presence of bone formation indicators-bone morphogenetic protein (BMP), osteocalcin (OCN) and osteopontin (OPN) within newly formed bone. Manufactured personalized construct acts as a "smart" responsive biomaterial capable of modulating the functionality and potential for the personalized bone reconstruction on a clinically relevant length scale.

Figure 1S. Change of the Ca concentration in the solution containing investigated nHAP granules with time. Figure 2S. Change of the Ca concentration with time in biological apatite (BioOss). Figure 3S. The correlation of the ALBO-OS compressive strenght and the time of the material’s soaking in Hank’s solution. Table 1S. Reference point indentation outcomes of the ALBOOS. MH – microhardness, ID 1st - 1st Cycle Indentation Distance; US 1st - 1st Cycle Unloading Slope; CID 1st -1st Cycle Creep Indentation Distance; TID - Total Indentation Distance; IDI - Indentation Distance Increase; Avg CID - Avg Creep Indentation Distance; Avg US - Average Unloading Slope; Avg US - Average Unloading Slope; Avg LS - Average Loading Slope; Avg ED - Average Energy Dissipated. Table 2S. Ph of nHAP after soaking in simulated body fluid. Figure 4S. Microacrhitectural and structural characteristics of nHAP in vitro and in contact with bone tissue in vivo. Adequate microstructure and surface nanotopography provide good environment for cells infiltration in vivo. Note the presence of porous paterns within material structure in vivo as well as the lamellar structure of ALBO-OS. Figure 5S. Schematic representation of the extruder design in custom made laboratory 3D printer: from technical reasons, 3D printer was modified to include two extruders: 1 – syringe extruder, 1.1 – glass syringe, 1.2 – external frame of the extruder 1, 1.3 – electrical heater coil, 1.4 –metal piston of the syringe, 1.5 – syringe nozzle (0,8mm in diameter), 1.6 – gears of the piston drive, 1.7 – piston drive motor with reduction, 1.8 – HAP PLA mixture, 2 – PLA extruder, 2.1 – heater block of the PLA extruder, 2.2 – extruder cooler, 2.3 – PLA extruder motor drive with reduction, 2.4 – PLA filament 1.75mm in diameter, 2.5 – PLA extruder nozzle 0,4mm in diameter. Figure 6S. Paste extruder attached to the head of the printer, with removed electrical heater coil, so the syringe with the metal piston can be visible. A) The

U četvrtoj nedelji, u primitivnoj usnoj duplji, zapaža se izuzetno visok mitotički indeks epitelnih ćelija, njihov broj se naglo povećava. U gornjoj i donjoj vilici nastaju epitelna zadebljanja koja se označavaju kao primitivne epitelne trake. Ova zadebljanja prate položaj budućeg alveolarnog nastavka maksile i mandibule. Iz primarnih traka nastaće dve strukture zubna gredica (lamina dentalis) i vestibularna gredica (lamina vestibularis). Iz lamine dentalis razviće se prvo po 10 zubnih pupoljaka mlečne denticije, a kasnije po 16 zubnih pupoljaka stalne denticije, dok će se iz lamine vestibularis razviti vestibulum gornje i donje vilice. Razvoj zuba je složen , kontinuiran proces koji prolazi kroz više faza: faza pupoljka ( faza inicijacije), faza kape (proliferacija), faza zvona (histodiferencijacija i morfodiferencijacija) i faza stvaranja krunice zuba (faza mineralizacije). Razvoj zuba započinje oko šeste nedelje intrauterinog života do početka treće decenije.

Homeostaza kože direktno zavisi od mehanizma kontinuiranog obnavljanja ćelijske populacije kože i njene sposobnosti regeneracije. U epidermisu je prisutna posebna populacija ćelija zadužena za proces samoobnavljanja kože, tzv. epidermalne matične ćelije koje imaju sposobnost proliferacije, migracije, diferencijacije i programirane ćelijske smrti. Ukoliko dođe do narušavanja ravnoteže između ovih procesa, može doći do maligne transformacije zdrave matične ćelije u kancersku matičnu ćeliju. Poznato je da za hemorezistenciju, metastaziranje i recidiviranje tumora odgovornost nosi posebna populaciju tumorskih ćelija koje se nazivaju kancerske matične ćelije. Istraživanja pokazuju da bazocelularni karcinom kože vodi poreklo od matičnih ćelija ispupčenja folikula dlake, infundibuluma dlake i interfolikularnog epidermisa. Bazocelularni karcinom (BCK) je najčešći maligni tumor kože, pa i ako retko metastazira karakteriše ga invazivni rast pri čemu infiltriše okolne strukture i dovodi do ozbiljnih funkcionalnih i estetskih defekata. U literaturi se kao jedan od ključnih faktora odgovornih za recidiviranje navodi neadekvatna širina margine resekcije tumora. Istraživanja su pokazala da je za primarne BCK na koži lica veličine do 20 mm preporučena širina margine 3 mm. Cilj ovog istraživanja bio je identifikacija i karakterizacija subpopulacije ćelija sa osobinama matičnosti izolovanih iz BCK-a i bliske margine od 3 mm, ispitivanjem proliferativnog, klonogenog i migratornog potencijala, analizom ekspresije embrionalnih, mezenhimskih i tumorskih markera, analizom biohemijske strukture ćelija, ispitivanjem sposobnosti diferencijacije u više ćelijskih linija kao i stepena otpornosti ćelija na dejstvo citostatika. U istraživanju je učestvovalo 13 pacijenata sa primarnim bazocelularnim karcinomom na koži lica veličine do 20 mm. Nakon detaljno uzete anamneze i potpisanog informisanog pristanka pristupalo se hirurškoj eksciziji tumorske promene, koja se smatra zlatnim standardom u tera, renewal and regeneration and the epidermis harbors a special cell population responsible for the process of self-renewal and regeneration of the skin, so called epidermal stem cells that have the ability to proliferate, migrate, differentiate, and undergo programmed cell death. If imbalance between these processes occurs, malignant transformation of healthy stem cell into the cancerous stem cell may happen. It is also known that a specific population of tumor cells called cancer stem cells is responsible for the hemoresistance, metastasis, and recurrence. Studies have shown that skin basal cell carcinoma is caused by stem cells of hair follicle, hair infundibulum and interfollicular epidermis. Basocellular carcinoma (BCC) is the most common malignant tumor of the skin, but it rarely gives metastases It is characterized by invasive growth, infiltrating surrounding structures and leading to serious functional and aesthetic defects. In the literature, inadequate margins are indicated as one of the key factors responsible for tumor recurrences. Studies have shown that for the primary facial skin BCC of less than 20 mm a margin of 3 mm is recommended. The aim of this study was to identify and characterize the cell subpopulation with stem characteristics whithin BCC and its margins (3 mm close) by testing proliferative, clonogenic and migratory potential, by analyzing the expression of embryonic, mesenchymal and tumor markers, by analizing biochemical structure of cells, by examining the differentiation potential of generated cell lines and by testing the degree of chemo-resistance. The study included 13 patients with primary BCC of face skin of less than 20 mm. Following a detailed anamnesis and a signed informed consent, the surgical excision which is considered a gold standard in BCC therapy, was done. A portion of the tumor tissue, of close margin (3 mm from the macroscopic tumor limit), and of healthy skin included in the resecion (at least 5mm from the macroscopic t

oviji podaci ukazuju na postojanje male subpopulacije kancerskih matičnih ćelija (KMĆ) koje su odgovorne za inicijaciju, progresiju i metastaziranje tumora. Do sada, su studije bile fokusirane isključivo na karakterizaciju ovih ćelijskih populacija unutar samog tumora, dok su margine tumora bile zanemarene, iako je poznato da histološki i molekularni status margina tumora može imati značajnu ulogu u toku bolesti. U ovoj studiji, primarne kulture ćelija tumora i margina dobijenih od pacijenata sa oralnim planocelularnim karcinomom su korišćene za ispitivanje ekspresije markera povezanih sa KMĆ (CD44, CD133, Oct-4, Sox2, Nanog), markera epitelno mezenhimske tranzicije (EMT) (E-kadherin, N-kadherin, Vimentin, ɑSMA, SLUG i SNAIL), a ispitivan je i klonalni, proliferativni i migracijski potencijal ova dva tipa ćelija. Stoga su ciljevi ove studije bili da se izoluju ćelije oralnog planocelularnog karcinoma i njegovih margina, uspostave primarne ćelijske kulture i ispitaju populacije ćelija sa karakteristikama kancerske matičnosti. Ćelijske kulture su dobijene iz 12 uzoraka tkiva (6 tumora i 6 margina). RNK je ekstrahovana i analiza ekspresije gena je urađena pomoću lančane reakcije polimeraze u realnom vremenu. Korišćene su i protočna citometrija, imunocitohemija, imunohistohemija, Raman mikro- spektroskopija, testovi formiranja sfera, ćelijske proliferacije, formiranja kolonija, migracije i MTT test citotoksičnosti, kako bi se u potpunosti okarakterisala ova dva tipa ćelija. Sa manjim odstupanjima, ćelije koje potiču od tumora i ćelije poreklom od margine pokazale su prisustvo markera matičnih ćelija CD133, Nanog, Sox2, CD44 i Oct-4, imale su sposobnost da formiraju sferoide i pokazale su hemorezistenciju. Takođe, svi ispitivani EMT markeri kao dodatni dokaz kancerske matičnosti, bili su eksprimirani u tumorskim i ćelijama margine, bez statistički značajne razlike (p> 0,05). Uz nekoliko izuzetaka, ekspresija EMT i KMĆ markera je bila viša u petoj pasaži u poređenju sa pr, CSC) are accountable for tumour initiation, progression and metastasis. Until now, studies were focused exclusively on the characterization of these cell populations within the tumour itself, while tumour margins were neglected, although it is known that the histological and molecular status of tumour margins may play a significant role in the course of the disease. In the present study tumor and margin cell cultures obtained from patients with oral squamous cell carcinoma were used to determine the expression patterns in the course of time, of CSC-related markers (CD44, CD133, Oct-4, Sox2, Nanog), epithelial to mesenchymal transition (EMT)-related markers (Vimentin, αSMA, SLUG and SNAIL), and features, i.e. the clonal, proliferative and migratory potential of the two types of cells. The aims of the study were to isolate cells from oral squamous cell carcinomas and their respective margins, to characterize these cells using CSC/EMT markers, to assess their self-renewal, proliferation and migration potential and determine their chemoresistance. Cell cultures were obtained from 12 tissue specimens (6 tumors and 6 margins). Total RNA was extracted and gene expression analysis was done by real-time PCR. Flow cytometry, immunocytometry, immunohistochemistry, Raman micro-spectroscopy, sphere formation, cell proliferation, colony forming, scratch wound healing and MTT assays were conducted to fully characterize the two cell types. With minor differences, cells originating from both tumors and tumor margins showed the presence of stem cell markers CD133, Nanog, Sox2, CD44, and Oct-4, had the capacity to form spheroids and showed chemoresistance/sensitivity. All the studied EMT markers were expressed in both tumor and margin cells, without statistically significant difference (p>0.05). With few exceptions, for both EMT and CSC markers, the expression was higher in the 5th passage compared to the 1st, probably as the consequence of culture enrichment with CSC in the course of

Dental cement materials have been developed with the aim to replace hard dental tissues. The first material used for pulp capping, root canal obturation, bifurcation perforation and apexification is calcium hydroxide (in 1920). A half century later, glass-ionomer cements began to suppress it as dentine substitutes. Finally, in the 1990s, calcium silicate (CS) material appeared in the dental research community as the most promising dentine substitute capable to adequately meet all clinical requirements. The aim of this paper is to present an overview of literature related to studies about CS materials taking into account their physical, chemical and biological properties and clinical applications. This review aims to discuss beneficial and adverse characteristics of CSs concerning interactions to the hard dentine and soft pulp/periodontal tissues. This review article deals with the literature data about currently commercially available CS concerning laboratory and clinical findings. 109 scientific articles were analyzed of which 62 references reported in vitro and 26 in vivo investigations while 21 references comprised reports, reviews and books dealing with both, in vitro and in vivo investigations. Although further data collection is necessary, CSs are promising materials that represent a gold standard for numerous dental clinical procedures.

renewal and regeneration and the epidermis harbors a special cell population responsible for the process of self-renewal and regeneration of the skin, so called epidermal stem cells that have the ability to proliferate, migrate, differentiate, and undergo programmed cell death. If imbalance between these processes occurs, malignant transformation of healthy stem cell into the cancerous stem cell may happen. It is also known that a specific population of tumor cells called cancer stem cells is responsible for the hemoresistance, metastasis, and recurrence. Studies have shown that skin basal cell carcinoma is caused by stem cells of hair follicle, hair infundibulum and interfollicular epidermis. Basocellular carcinoma (BCC) is the most common malignant tumor of the skin, but it rarely gives metastases It is characterized by invasive growth, infiltrating surrounding structures and leading to serious functional and aesthetic defects. In the literature, inadequate margins are indicated as one of the key factors responsible for tumor recurrences. Studies have shown that for the primary facial skin BCC of less than 20 mm a margin of 3 mm is recommended. The aim of this study was to identify and characterize the cell subpopulation with stem characteristics whithin BCC and its margins (3 mm close) by testing proliferative, clonogenic and migratory potential, by analyzing the expression of embryonic, mesenchymal and tumor markers, by analizing biochemical structure of cells, by examining the differentiation potential of generated cell lines and by testing the degree of chemo-resistance. The study included 13 patients with primary BCC of face skin of less than 20 mm. Following a detailed anamnesis and a signed informed consent, the surgical excision which is considered a gold standard in BCC therapy, was done. A portion of the tumor tissue, of close margin (3 mm from the macroscopic tumor limit), and of healthy skin included in the resecion (at least 5mm from the macroscopic t, Homeostaza kože direktno zavisi od mehanizma kontinuiranog obnavljanja ćelijske populacije kože i njene sposobnosti regeneracije. U epidermisu je prisutna posebna populacija ćelija zadužena za proces samoobnavljanja kože, tzv. epidermalne matične ćelije koje imaju sposobnost proliferacije, migracije, diferencijacije i programirane ćelijske smrti. Ukoliko dođe do narušavanja ravnoteže između ovih procesa, može doći do maligne transformacije zdrave matične ćelije u kancersku matičnu ćeliju. Poznato je da za hemorezistenciju, metastaziranje i recidiviranje tumora odgovornost nosi posebna populaciju tumorskih ćelija koje se nazivaju kancerske matične ćelije. Istraživanja pokazuju da bazocelularni karcinom kože vodi poreklo od matičnih ćelija ispupčenja folikula dlake, infundibuluma dlake i interfolikularnog epidermisa. Bazocelularni karcinom (BCK) je najčešći maligni tumor kože, pa i ako retko metastazira karakteriše ga invazivni rast pri čemu infiltriše okolne strukture i dovodi do ozbiljnih funkcionalnih i estetskih defekata. U literaturi se kao jedan od ključnih faktora odgovornih za recidiviranje navodi neadekvatna širina margine resekcije tumora. Istraživanja su pokazala da je za primarne BCK na koži lica veličine do 20 mm preporučena širina margine 3 mm. Cilj ovog istraživanja bio je identifikacija i karakterizacija subpopulacije ćelija sa osobinama matičnosti izolovanih iz BCK-a i bliske margine od 3 mm, ispitivanjem proliferativnog, klonogenog i migratornog potencijala, analizom ekspresije embrionalnih, mezenhimskih i tumorskih markera, analizom biohemijske strukture ćelija, ispitivanjem sposobnosti diferencijacije u više ćelijskih linija kao i stepena otpornosti ćelija na dejstvo citostatika. U istraživanju je učestvovalo 13 pacijenata sa primarnim bazocelularnim karcinomom na koži lica veličine do 20 mm. Nakon detaljno uzete anamneze i potpisanog informisanog pristanka pristupalo se hirurškoj eksciziji tumorske promene, koja se smatra zlatnim standardom u tera

Zubna pulpa je visoko specijalizovano tkivo sa protektivnom i formativnom ulogom u odnosu na zub. Cilj ovog rada bio je da prikaže ulogu odontoblasta i odontoblastima sličnih ćelija u odbrambenim i reparatornim procesima u pulpi u svetlu savremene literature. Koristili smo radove dostupne preko različitih baza podataka: PubMed, Springer, Science Direct, Scopus za vremenski period do 2018. godine. Pretraživanja smo radili koristeći sledeće ključne reči: dentinsko-pulpni kompleks, regeneracija, tkivni inženjering, nosači (skafoldi), matične (stem) ćelije i faktori rasta. Dvadeset tri rada izabrana su za evaluaciju uloge odontoblasta i odontoblastima sličnih ćelija u odbrambenim i reparatornim procesima u pulpi. Ovaj rad sumira trenutna znanja o ulozi navedenih ćelija kao i njihovoj interakciji sa nosačima i faktorima rasta u regenerativnim i reparatornim procesima.

Background/Aim. There are very few data about the effects of endogenous growth factors in vital pulp therapy, and still they are often controversial. The aim of the study was to evaluate the effects of platelet rich plasma (PRP) in conjugation with hydroxyapatite (HAP), as pulp capping materials, to root and periodontium formation. Methods. Eight young monkeys (Cercopithecus Aethiops) with permanent dentition and incomplete root formation were involved in this study. After pulpotomy, the pulp lesion was capped with calcium hydroxide (control), hydroxyapatite (experimental group I) or hydroxyapatite in conjugation with PRP (experimental group II). Six months later, the animals were sacrificed, the tissue was removed en block, and prepared for the histological analysis in a routine way. Results. The results of the histological analysis revealed that healing process was characterised by dentin bridge formation, maintained morphological and functional integrity of dental pulp and complete formation of dental root and surrounding periodontium. The inflammatory reaction was scored as mild to moderate, in almost all the samples in all groups, suggesting the biocompatibility of the used materials. Conclusion. Materials used in this study are convenient as capping agents, contributing maintaining the integrity of the pulp tissue and facilitating root and periodontium formation. According to histological data it could be suggested that hydroxyapatite in conjugation with endogenous growth factors, represents superior alternative to other materials used in this study., Uvod/Cilj. Podaci o primeni endogenih faktora rasta u terapiji vitalne pulpe zuba sa nezavršenim rastom korena su veoma oskudni i često kontraverzni. Cilj ovog rada bio je da se ispita uticaj plazme bogate trombocitima (PRP) u kombinaciji sa hidroksiapatitom (HAP), kao materijala za direktno prekrivanje pulpe, na završetak rasta korena i formiranje okolnog parodoncijuma. Metode. Istraživanje je obavljeno na osam mladih majmuna Cercopithecus Aethiops. Sve životinje imale su zube stalne denticije, sa nezavršenim rastom korena. Nakon trepanacije pulpnog prostora, pulpa je uklonjena do nivoa gleđnocementnog spoja, a lezija u pulpi prekrivena je kalcijum hidroksidom (kontrolna grupa), hidroksiapatitom (eksperimentna grupa I) i hidroksiapatitom u kombinaciji sa autogenim PRP faktorom (eksperimentna grupa II). Šest meseci nakon amputacije pulpe, životinje su žrtvovane, a tkivo za histološku analizu uzeto je u obliku blok sekcije i pripremljeno za mikroskopsku analizu. Rezultati. Zarastanje rane u pulpno-dentinskom kompleksu u obe eksperimentne i u kontrolnoj grupi bilo je karakterisano stvaranjem dentinskog mostića procesom reparativne dentinogeneze, očuvanjem morfološkog i funkcijskog integriteta pulpe, kao i završetkom rasta korena i stvaranjem okolnog parodoncijuma. U većini uzoraka obe grupe, zapaljenska reakcija ocenjena je kao blaga do umerena, što govori u prilog biokompatibilnosti primenjenih materijala. Zaključak. Svi primenjeni materijali pogodni su za direktno prekrivanje pulpe, doprinose očuvanju njenog morfološkog i funkcionalnog integriteta i omogućavaju završetak rasta korena i formiranje okolnog parodoncijuma. Ipak, povoljniji rezultati dobijeni su u grupi koja je tretirana HAP/PRP, pa se može reći da HAP obogaćen endogenim faktorima rasta predstavlja superiorniju alternativu u odnosu na ostale materijale primenjene u ovoj studiji.

This study was conducted to observe the response of dog's dental pulp to hydrpxylapatite (Hap) and calcium hydroxide when used as pulp capping materials. After the pulps of 22 teeth were exposed, they were capped with either Hap or calcium hydroxide. Histological analysis was performed 8 weeks after treatment. Results showed that pulp exposure caused irreversible injury of odontoblasts, which were subsequently replaced by similar, odontoblast-like cells. These cells were able for reparative dentin bridge formation in 6 cases treated with calcium hydroxide and almost all the cases treated with hydroxylapatite. The presence of odontoblast-like cells seemed to be crucial for reparative dentinogenesis. The capping material was of less importance. In conclusion neither calcium hydroxide nor hydrxylapatite had completely satisfied all the requirements of an ideal capping material, although Hap can be recognized as a superior alternative to calcium hydroxide., Cilj ovog rada je bio ispitivanje odgovora zubne pulpe pasa nakon njenog direktnog prekrivanja hidroksilapatitom (Hap) ili kalcijum hidroksidom. U eksperimentu su korišćena 22 zuba kod kojih je nakon arteficijelnog otvaranja, zubna pulpa prekrivana Hap-om ili kalcijum-hidroksidom. Osam nedelja nakon prekrivanja, urađena je histološka analiza. Dobijeni rezultati su ukazali da je tokom arteficijelnog otvaranja pulpe došlo do ireverzibilnog oštećenja odontoblasta i njihove zamene ćelijama sličnim odontoblastima. Odontoblastima-slične ćelije stvorile su mostić reparativnog dentina u 6 uzoraka iz grupe tretirane kalcijum hidroksidom i skoro svim uzorcima tretiranih Hap-om. Uočeno je da je prisustvo odontoblastima- sličnih ćelija presudno za uspeh reparativne dentinogeneze, dok je vrsta korišćenog materijala za direktno prekrivanje, bila od manje važnosti. Pri tome ni hidroksilapatit ni kalcijum hidroksid ne zadovoljavaju sve zahteve koji se postavljaju pred idealne materijale za direktno punjenje. Hap ipak predstavlja superiorniju alternativu u odnosu na kalcijum hidroksid.

Introduction Direct pulp capping is an important therapeutic method that has goal to provide formation of dentin bridge and healing process of the pulp. The aim of this study was to investigate the effects of new nanostructural materials based on calcium silicate systems and hydroxyapatite on exposed dental pulp in Vietnamese pigs. Material and Methods The study was conducted on 30 teeth of two Vietnamese pigs (Sus scrofa verus). On buccal surfaces of incisors, canines and first premolars, class V cavities were prepared with a small round bur and pulp horn was exposed. In the first experimental group (10 teeth) the perforation was covered with new nanostructural material based on calcium silicate systems (CS). In the second experimental group, the perforation was covered with compound of calcium silicate systems and hydroxyapatite (HA-CS) (10 teeth). In the control group, exposed pulp was covered with Pro Root MTA® (Dentsply Tulsa Dental, Johnson City, TN, USA) (10 teeth). All cavities were restored with glass ionomer cement (GC Fuji VIII, GC Corporation, Tokyo, Japan). Observation period was 28 days. After sacrificing the animals, histological preparations were done to analyze the presence of dentin bridge, inflammatory reaction of the pulp, pulp tissue reorganization and the presence of bacteria. Results Dentin bridge was observed in all teeth (experimental and control groups). Inflammation of the pulp was mild to moderate in all groups. Neoangiogenesis and many odontoblast like cells responsible for dentin bridge formation were detected. Necrosis was not observed in any case, neither the presence of Gram-positive bacteria in the pulp. Conclusion Histological analysis indicated favorable therapeutic effects of new nanostructural materials based on calcium silicate systems and hydroxyapatite for direct pulp capping in teeth of Vietnamese pigs., Uvod Direktno prekrivanje pulpe je važan terapijski postupak koji ima zadatak da obezbedi zatvaranje pulpne komore i omogući proces zarastanja. Cilj ovog rada je bio da se ispita efekat novih nanostrukturnih materijala na bazi kalcijum-silikatnih sistema i hidroksiapatita na eksponiranu pulpu zuba vijetnamskih svinja. Materijal i metode rada Istraživanje je sprovedeno na 30 zuba kod dve vijetnamske svinje (Sus scrofa verus). Na vestibularnim površinama sekutića, očnjaka i prvih premolara urađene su preparacije kaviteta V klase, pri čemu je malim okruglim svrdlom napravljena namerna eksploracija komore pulpe. U prvoj eksperimentalnoj grupi (10 zuba) perforacija je prekrivana novim nanostrukturnim materijalom na bazi kalcijum-silikatnih sistema (CS). U drugoj eksperimentalnoj grupi (10 zuba) perforacija je prekrivana smešom kalcijum-silikatnog sistema i hidroksiapatita (HA-CS). U kontrolnoj grupi (10 zuba) perforacija je prekrivana sa MTA® (Dentsply Tulsa Dental, Džonson Siti, Tenesi, SAD). Svi kaviteti su restaurirani glas-jonomer cementom (GC Fuji VIII, GC Corporation, Tokio, Japan). Opservacioni period iznosio je 28 dana. Nakon žrtvovanja životinja napravljeni su histološki preparati na kojima su analizirani postojanje dentinskog mostića, inflamatorna reakcija pulpe, reorganizacija pulpnog tkiva i prisustvo bakterija. Rezultati Na svim zubima eksperimentalnih grupa i kontrolne grupe zabeleženo je stvaranje dentinskog mostića. Zapaljenje pulpe je bilo blago do umereno i u eksperimentalnim i u kontrolnoj grupi. Uočeni su znaci neoangiogeneze i mnoštvo ćelija sličnih odontoblastima koje su odgovorne za stvaranje dentinskog mostića. Nekroza nije zabeležena ni u jednom slučaju, kao ni prisustvo gram-pozitivnih bakterija u pulpi. Zaključak Histološka analiza je ukazala na povoljne terapijske efekte novih nanostrukturnih materijala na bazi kalcijum-silikatnih sistema i hidroksiapatita u direktnom prekrivanju pulpe zuba vijetnamskih svinja.

Osnovni cilj terapije mladih stalnih zuba sa eksponiranom pulpom, koja nastaje kao posledica dentalne traume ili progresije karijesa, je očuvanje vitaliteta i funkcije oštećene pulpe. Terapijski postupak, uz pravilno postavljenu indikaciju, najčešće uključuje primenu metoda direktnog prekrivanja pulpe ili vitalne pulpotomije. Direktno prekrivanje pulpe (DPP) je terapijski postupak aplikacije leka na eksponiranu pulpu zuba sa ciljem da obezbedi zatvaranje pulpne komore i omogući proces zarastanja. Tretman obuhvata zatvaranje rane bioaktivnim materijalom koji pospešuje ozdravljenje pulpe formiranjem reparatornog dentina tj, dentinskog mosta na mestu povrede. Ozdravljenje pulpe podrazumeva migraciju stem/progenitor ćelija pulpe do mesta povrede i njihovu proliferaciju i diferencijaciju u ćelije slične odontoblastima. Ove ćelije sekretuju matriks tercijarnog dentina, sa posledičnim formiranjem reparatornog dentinskog mosta. Kako je uspeh terapije DPP često veoma neizvestan, a idealan materijal za DPP još uvek ne postoji, poslednjih decenija se ulažu veliki napori istraživača i kliničara u razvoj biomaterijala koji bi pored biokompatibilnosti, trebalo da odlikuje i bioaktivnost i bioinduktivnost. Iako danas MTA još uvek predstavlja zlatni standard u DPP, čine se napori kako bi se prevazišli nedostaci ovog materijala (dugo vreme vezivanja, teškoće u rukovanju i aplokaciji, visoka cena na tržištu) i uvođenjem novih materijala unapredila terapijska procedura DPP. Mogućnosti za to svakako postoje u biomimetičkim regenerativnim procedurama, tkivnom inžinjeringu i nanotehnologiji. Biomimetički terapijski pristup i moguća primena amelogenina-gleđnog proteina u tkivnoj regeneraciji, odnosno primena novih koncepata aktivne regeneracije i tkivnog inžinjeringa, može značajno unaprediti terapijske rezultate. Emdogain je materijal novije generacije koji u svom sastavu sadrži gleđne proteine i faktore rasta i kao takav se dugi niz godina uspešno upotrebljava u regenerativnoj terapiji, The purpose of treating permanent teeth with exposed pulp, which can be a result of trauma or dental caries progression, is to preserve the vitality and function of the damaged pulp. The therapeutic procedure, along with an adequate indication, most often involves the use of methods of direct pulp capping or vital pulpotomy. Direct pulp capping (DPC) is a therapeutic aplication of drug on exposed dental pulp in order to ensure the closure of the pulp chamber and allow healing process. The treatment includes wound closure with a bioactive material that accelerates healing of the pulp by forming a reparatory dentin or dentin bridge at the site of injury. Recovery of the pulp involves migration of stem/progenitor cells of the pulp to the site of the injury and their proliferation and differentiation into odontoblasts like cells. These cells secrete tertiary dentin matrix with subsequent formation of a reparatory dentin bridge. The success of DPC therapy is often very uncertain and the ideal material does not yet exist. Recent decades have seen a considerable effort by researchers and clinicians in the development of biomaterials which should be characterized not only by biocompatibility, but by bioactivity and bioinductivity. Although MTA still represents the gold standard in DPC today, efforts have been made to overcome the disadvantages of this material (long setting time, difficult handling and application, high market price) along with the introduction of new materials which improved the therapeutic procedure of DPC. Biomimetic regenerative procedures, tissue engineering and nanotechnology provide such possibilities. Biomimetic therapeutic approach and application of amelogenin-enamel proteins in tissue regeneration or the application of new procedures by active regeneration and tissue engineering, can significantly improve the therapeutic results. Emdogain is a newer generation material which consists of enamel proteins and growth factors. For many years it has be

The purpose of treating permanent teeth with exposed pulp, which can be a result of trauma or dental caries progression, is to preserve the vitality and function of the damaged pulp. The therapeutic procedure, along with an adequate indication, most often involves the use of methods of direct pulp capping or vital pulpotomy. Direct pulp capping (DPC) is a therapeutic aplication of drug on exposed dental pulp in order to ensure the closure of the pulp chamber and allow healing process. The treatment includes wound closure with a bioactive material that accelerates healing of the pulp by forming a reparatory dentin or dentin bridge at the site of injury. Recovery of the pulp involves migration of stem/progenitor cells of the pulp to the site of the injury and their proliferation and differentiation into odontoblasts like cells. These cells secrete tertiary dentin matrix with subsequent formation of a reparatory dentin bridge. The success of DPC therapy is often very uncertain and the ideal material does not yet exist. Recent decades have seen a considerable effort by researchers and clinicians in the development of biomaterials which should be characterized not only by biocompatibility, but by bioactivity and bioinductivity. Although MTA still represents the gold standard in DPC today, efforts have been made to overcome the disadvantages of this material (long setting time, difficult handling and application, high market price) along with the introduction of new materials which improved the therapeutic procedure of DPC. Biomimetic regenerative procedures, tissue engineering and nanotechnology provide such possibilities. Biomimetic therapeutic approach and application of amelogenin-enamel proteins in tissue regeneration or the application of new procedures by active regeneration and tissue engineering, can significantly improve the therapeutic results. Emdogain is a newer generation material which consists of enamel proteins and growth factors. For many years it has be, Osnovni cilj terapije mladih stalnih zuba sa eksponiranom pulpom, koja nastaje kao posledica dentalne traume ili progresije karijesa, je očuvanje vitaliteta i funkcije oštećene pulpe. Terapijski postupak, uz pravilno postavljenu indikaciju, najčešće uključuje primenu metoda direktnog prekrivanja pulpe ili vitalne pulpotomije. Direktno prekrivanje pulpe (DPP) je terapijski postupak aplikacije leka na eksponiranu pulpu zuba sa ciljem da obezbedi zatvaranje pulpne komore i omogući proces zarastanja. Tretman obuhvata zatvaranje rane bioaktivnim materijalom koji pospešuje ozdravljenje pulpe formiranjem reparatornog dentina tj, dentinskog mosta na mestu povrede. Ozdravljenje pulpe podrazumeva migraciju stem/progenitor ćelija pulpe do mesta povrede i njihovu proliferaciju i diferencijaciju u ćelije slične odontoblastima. Ove ćelije sekretuju matriks tercijarnog dentina, sa posledičnim formiranjem reparatornog dentinskog mosta. Kako je uspeh terapije DPP često veoma neizvestan, a idealan materijal za DPP još uvek ne postoji, poslednjih decenija se ulažu veliki napori istraživača i kliničara u razvoj biomaterijala koji bi pored biokompatibilnosti, trebalo da odlikuje i bioaktivnost i bioinduktivnost. Iako danas MTA još uvek predstavlja zlatni standard u DPP, čine se napori kako bi se prevazišli nedostaci ovog materijala (dugo vreme vezivanja, teškoće u rukovanju i aplokaciji, visoka cena na tržištu) i uvođenjem novih materijala unapredila terapijska procedura DPP. Mogućnosti za to svakako postoje u biomimetičkim regenerativnim procedurama, tkivnom inžinjeringu i nanotehnologiji. Biomimetički terapijski pristup i moguća primena amelogenina-gleđnog proteina u tkivnoj regeneraciji, odnosno primena novih koncepata aktivne regeneracije i tkivnog inžinjeringa, može značajno unaprediti terapijske rezultate. Emdogain je materijal novije generacije koji u svom sastavu sadrži gleđne proteine i faktore rasta i kao takav se dugi niz godina uspešno upotrebljava u regenerativnoj terapiji