NIR-responsive ROS generating core and ROS-triggered 5'-Deoxy-5-fluorocytidine releasing shell structured water-swelling microgel for locoregional combination cancer therapy.

Combination chemotherapy now becomes the most standard cancer treatment protocol. Here, we present a core-shell type polymeric microgel (CSPM) which combines photodynamic and chemo therapeutic modalities in one-pot system. CSPM localizes in the malignant lesion after intratumoral injection, releases reactive oxygen species (ROS) and anticancer drug (5'-deoxy-5-fluorocytidine; DFCR) under the near-infrared (NIR) laser treatment. Pheophorbide A (PheoA)-linked poly(hydroxyethyl methacrylate) (poly-HEMA) was designated to a ROS-generating core, and chemically covered with a chitosan shell. In addition, phenylboronic acid was employed in chitosan shells and linked to DFCR to form an ROS cleavable boronic ester. The core-shell structure of CSPM was determined by transmission electron microscopy. NIR-responsive photodynamic ROS generation was confirmed by the oxidative reduction of 9,10-dimethylanthracene (a fluorescent dye), and the cascadic release of DFCR by ROS was confirmed by a release study and a live and dead cell imaging study. Typically, poly-HEMA cored microgel increased its volume by 48.9-fold after absorption of body fluid. This swelling property ensured CSPM was retained in tumor tissues after subtumoral injection and the suitability of CSPM for locoregional phototherapy. The therapeutic effect of CSPM was attributed to the combined, cascadic deliveries of cytotoxic ROS and DFCR and confirmed by growth inhibition studies in in vitro pancreatic cancer cells and in vivo colon cancer mouse model.

Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release.

To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing ß-cyclodextrin (ß-CD) (pHEMA/MMA/ß-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/ß-CD copolymers containing different ratios of ß-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing ß-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering ß-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, ß-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/ß-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery.

Polvo de metacrilato en la cicatrización de heridas / Metacrylate powder for wound healing

Introducción. La estrategia terapéutica ideal para la resolución clínica de las heridas crónicas se basa en la promoción de la cicatrización. Un nuevo apósito de polvo de metacrilato ha mostrado resultados clínicos prometedores en el tratamiento de las úlceras cutáneas. Objetivo. Evaluar la eficacia del polvo de metacrilato estéril. Metodología. A través de un caso clínico de una paciente con ulcera crónica que había estado presente durante más de 6 meses después de una lesión accidental. Resultados. Se consigue una buena evolución de la herida y la epitelización completa de la úlcera, en 40 días del tratamiento. Discusión. Las úlceras crónicas de los miembros inferiores tienen un impacto importante en la calidad de vida de los pacientes y suponen una carga económica significativa para el sistema sanitario. El uso de polímeros de metacrilato en el cuidado de heridas no es reciente, pues se propuso hace treinta años. Conclusiones. La utilización de polvo liofilizado estéril proporciona un tratamiento seguro y muy efectivo para la mayoría de los pacientes con heridas de difícil epitelización. Este método disminuye el dolor y el exudado y acorta el periodo de cicatrización. Ha de ser la primera elección de tratamiento en estas lesiones. Es preciso un abordaje integral y multidisciplinar de los casos de difícil resolución, donde los enfermeros juegan un papel fundamental (AU)

Introduction. The ideal therapeutic strategy for the clinical resolution of chronic wounds is based on promoting healing. A new methacrylate powder dressing has shown promising clinical results in the treatment of skin ulcers. Objective. Evaluate the effectiveness of sterile methacrylate powder in the treatment of chronic skin ulcers. Methodology. Clinical case study of a patient with chronic leg ulcer, that remained unhealed 6 months after the accidental injury. Results. Within 40 days of treatment the wound had evolved positively, achieving the complete epithelialization of the ulcer. Discussion: Chronic lower-limb ulcerations have a negative impact on the quality of life of patients and pose a significant economic burden on healthcare systems. The use of methacrylate polymers in wound care is not recent; it was already proposed thirty years ago. Conclusions. The use of sterile lyophilized powder provides a safe and very effective treatment for the majority of patients’ wounds which show difficult epithelialization. This method reduces pain and exudation, shortens the healing period, and should be the first-choice treatment for these lesions. Nurses play a fundamental role in managing cases of chronic wounds, where a comprehensive and multidisciplinary approach is necessary (AU)

GelMA-Encapsulated hDPSCs and HUVECs for Dental Pulp Regeneration.

Pulpal revascularization is commonly used in the dental clinic to obtain apical closure of immature permanent teeth with thin dentinal walls. Although sometimes successful, stimulating bleeding from the periapical area of the tooth can be challenging and in turn may deleteriously affect tooth root maturation. Our objective here was to define reliable methods to regenerate pulp-like tissues in tooth root segments (RSs). G1 RSs were injected with human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) encapsulated in 5% gelatin methacrylate (GelMA) hydrogel. G2 RSs injected with acellular GelMA alone, and G3 empty RSs were used as controls. White mineral trioxide aggregate was used to seal one end of the tooth root segment, while the other was left open. Samples were cultured in vitro in osteogenic media (OM) for 13 d and then implanted subcutaneously in nude rats for 4 and 8 wk. At least 5 sample replicates were used for each experimental group. Analyses of harvested samples found that robust pulp-like tissues formed in G1, GelMA encapsulated hDPSC/HUVEC-filled RSs, and less cellularized host cell-derived pulp-like tissue was observed in the G2 acellular GelMA and G3 empty RS groups. Of importance, only the G1, hDPSC/HUVEC-encapsulated GelMA constructs formed pulp cells that attached to the inner dentin surface of the RS and infiltrated into the dentin tubules. Immunofluorescent (IF) histochemical analysis showed that GelMA supported hDPSC/HUVEC cell attachment and proliferation and also provided attachment for infiltrating host cells. Human cell-seeded GelMA hydrogels promoted the establishment of well-organized neovasculature formation. In contrast, acellular GelMA and empty RS constructs supported the formation of less organized host-derived vasculature formation. Together, these results identify GelMA hydrogel combined with hDPSC/HUVECs as a promising new clinically relevant pulpal revascularization treatment to regenerate human dental pulp tissues.

[LOXOCELES BITE WOUND TREATMENT WITH SYNTHETIC POLYMER MATRIX]. / Herida por picadura de loxosceles tratada con una matriz sintética de polímeros nueva perspectiva en la cura avanzada de heridas complejas.

Loxocelism is a toxic condition produces by the venom inoculated by the bit of the recluse spider (genus Loxosceles). In can appear in two clinical forms: cutaneous loxocelism and viscerocutaneous Ioxocelim. The species Loxoceles rufescens, found in Spain, is responsible of cases of cutaneous loxocelism. Cutaneous loxocelism starts with an itch, later giving rise to intense pain, and it later takes either a more or less severe necrotic form or an edematous form. The latter, with a better prognosis, is the one we focus on here. The diagnosis is clinical. The systemic treatment consists in analgesics, antihistamines, corticosteroids, broad-spectrum antibiotics, and dapsone in severe cases. The local treatment is based on the cleaning and debridement of the wound, and in advanced treatments for complex wounds. It is not uncommon that such wounds require skin grafting. We present the case of an 18-year female bitten by a loxosceles on the dorsal area of the foot. She developed a deep tissue necrosis in the area. She presented systemic complications such as leucocitosis, fever, local infection and cellulitis. Systemic treatment and hospitalization were required, as well as advanced therapeutic care. Finally, cutaneous integrity was restored after 84 days.

A comparison of portal vein embolization with poly(2-hydroxyethylmethacrylate) and a histoacryl/lipiodol mixture in patients scheduled for extended right hepatectomy.

To determine whether PHEMA [poly(2-hydroxyethylmethacrylate)] is suitable for portal vein embolization in patients scheduled to right hepatectomy and whether it is as effective as the currently used agent (a histoacryl/lipiodol mixture). Two groups of nine patients each scheduled for extended right hepatectomy for primary or secondary hepatic tumor, had right portal vein embolization in an effort to induce future liver remnant (FLR) hypertrophy. One group had embolization with PHEMA, the other one with the histoacryl/lipiodol mixture. In all patients, embolization was performed using the right retrograde transhepatic access. Embolization was technically successful in all 18 patients, with no complication related to the embolization agent. Eight patients of either group developed FLR hypertrophy allowing extended right hepatectomy. Likewise, one patient in each group had recanalization of a portal vein branch. Histology showed that both embolization agents reach the periphery of portal vein branches, with PHEMA penetrating somewhat deeper into the periphery. PHEMA has been shown to be an agent suitable for embolization in the portal venous system comparable with existing embolization agent (histoacryl/lipiodol mixture).

The use of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel to repair a T10 spinal cord hemisection in rat: a behavioural, electrophysiological and anatomical examination.

There have been considerable interests in attempting to reverse the deficit because of an SCI (spinal cord injury) by restoring neural pathways through the lesion and by rebuilding the tissue network. In order to provide an appropriate micro-environment for regrowing axotomized neurons and proliferating and migrating cells, we have implanted a small block of pHPMA [poly N-(2-hydroxypropyl)-methacrylamide] hydrogel into the hemisected T10 rat spinal cord. Locomotor activity was evaluated once a week during 14 weeks with the BBB rating scale in an open field. At the 14th week after SCI, the reflexivity of the sub-lesional region was measured. We also monitored the ventilatory frequency during an electrically induced muscle fatigue known to elicit the muscle metaboreflex and increase the respiratory rate. Spinal cords were then collected, fixed and stained with anti-ED-1 and anti-NF-H antibodies and FluoroMyelin. We show in this study that hydrogel-implanted animals exhibit: (i) an improved locomotor BBB score, (ii) an improved breathing adjustment to electrically evoked isometric contractions and (iii) an H-reflex recovery close to control animals. Qualitative histological results put in evidence higher accumulation of ED-1 positive cells (macrophages/monocytes) at the lesion border, a large number of NF-H positive axons penetrating the applied matrix, and myelin preservation both rostrally and caudally to the lesion. Our data confirm that pHPMA hydrogel is a potent biomaterial that can be used for improving neuromuscular adaptive mechanisms and H-reflex responses after SCI.

The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues.

BACKGROUND & AIMS: Copolymers of hydroxyethyl methacrylate and styrene sulfonate complex with isolated gliadin (the toxic fraction of gluten) and prevent damage to the intestinal barrier in HLA-HCD4/DQ8 mice. We studied the activity toward gluten and hordein digestion and biologic effects of poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS)). We also investigated the effect of gliadin complex formation in intestinal biopsy specimens from patients with celiac disease. METHODS: We studied the ability of P(HEMA-co-SS) to reduce digestion of wheat gluten and barley hordein into immunotoxic peptides using liquid chromatography-mass spectrometry. The biodistribution and pharmacokinetic profile of orally administered P(HEMA-co-SS) was established in rodents using tritium-labeled polymer. We assessed the capacity of P(HEMA-co-SS) to prevent the immunologic and intestinal effects induced by a gluten-food mixture in gluten-sensitized HLA-HCD4/DQ8 mice after short-term and long-term administration. We measured the effects of gliadin complex formation on cytokine release ex vivo using intestinal biopsy specimens from patients with celiac disease. RESULTS: P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein in vitro, thereby decreasing formation of toxic peptides associated with celiac disease. After oral administration to rodents, P(HEMA-co-SS) was predominantly excreted in feces, even in the presence of low-grade mucosal inflammation and increased intestinal permeability. In gluten-sensitized mice, P(HEMA-co-SS) reduced paracellular permeability, normalized anti-gliadin immunoglobulin A in intestinal washes, and modulated the systemic immune response to gluten in a food mixture. Furthermore, incubation of P(HEMA-co-SS) with mucosal biopsy specimens from patients with celiac disease showed that secretion of tumor necrosis factor-α was reduced in the presence of partially digested gliadin. CONCLUSIONS: The copolymer P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein and attenuated the immune response to gluten in a food mixture in rodents. It might be developed to prevent or reduce gluten-induced disorders in humans.

Bioinspired imprinted PHEMA-hydrogels for ocular delivery of carbonic anhydrase inhibitor drugs.

Hydrogels with high affinity for carbonic anhydrase (CA) inhibitor drugs have been designed trying to mimic the active site of the physiological metallo-enzyme receptor. Using hydroxyethyl methacrylate (HEMA) as the backbone component, zinc methacrylate, 1- or 4-vinylimidazole (1VI or 4VI), and N-hydroxyethyl acrylamide (HEAA) were combined at different ratios to reproduce in the hydrogels the cone-shaped cavity of the CA, which contains a Zn(2+) ion coordinated to three histidine residues. 4VI resembles histidine functionality better than 1VI, and, consequently, pHEMA-ZnMA(2) hydrogels bearing 4VI moieties were those with the greatest ability to host acetazolamide or ethoxzolamide (2 to 3 times greater network/water partition coefficient) and to sustain the release of these antiglaucoma drugs (50% lower release rate estimated by fitting to the square root kinetics). The use of acetazolamide as template during polymerization did not enhance the affinity of the network for the drugs. In addition to the remarkable improvement in the performance as controlled release systems, the biomimetic hydrogels were highly cytocompatible and possessed adequate oxygen permeability to be used as medicated soft contact lenses or inserts. The results obtained highlight the benefits of mimicking the structure of the physiological receptors for the design of advanced drug delivery systems.

Biocompatible hydrogels in spinal cord injury repair.

Spinal cord injury results in a permanent neurological deficit due to tissue damage. Such a lesion is a barrier for "communication" between the brain and peripheral tissues, effectors as well as receptors. One of the primary goals of tissue engineering is to bridge the spinal cord injury and re-establish the damaged connections. Hydrogels are biocompatible implants used in spinal cord injury repair. They can create a permissive environment and bridge the lesion cavities by providing a scaffold for the regeneration of neurons and their axons, glia and other tissue elements. The advantage of using artificial materials is the possibility to modify their physical and chemical properties in order to develop the best implant suitable for spinal cord injury repair. As a result, several types of hydrogels have been tested in experimental studies so far. We review our work that has been done during the last 5 years with various types of hydrogels and their applications in experimental spinal cord injury repair.

Poly(2-hydroxyethyl methacrylate) emboli with increased haemostatic effect for correction of haemorrhage of complex origin in endovascular surgery of children.

Poly(2-hydroxyethyl methacrylate) (PHEMA) embolization particles with enhanced haemostatic properties were prepared by bulk or suspension polymerisation of 2-hydroxyethyl methacrylate (HEMA) followed by particle soaking in ethamsylate solution. The particles accelerated thrombus formation as evidenced by blood analysis of rabbits with implanted emboli. Usefulness of both spherical and cylindrical PHEMA particles with enhanced haemostatic effect was demonstrated on the embolization of arterial anastomosis, fistulas of the lower extremity and abdominal cavity, haemangioma and arteriovenous malformation of the head of several children.

[Biological dressing with human hair keratin-collagen sponge-poly 2-hydroxyethyl methacrylate composite promotes burn wound healing in SD rats].

OBJECTIVE: To develop a composite material containing human hair keratin (HHK), collagen sponge (inner layer) and poly 2-hydroxyethyl methacrylate (PHEMA) film that allows sustained release of polydatin and test its effect as a biological dressing in promoting burn wound healing in SD rats. METHODS: Three HHK materials with fast, moderate, and low degradation rates were mixed at the ratio of 4:3:3 to prepare a reticular structure, which was processed into a composite material with bovine tendon-derived collagen sponge, and further complexed with HEMA film containing PD prepared by polymerization. Degree II burn wound was induced in SD rats by scalding and within postburn day 2-5, the wounds were cleansed and covered with the composite material or with glutaraldehyde-treated porcine skin (positive control). At week 1, 2, 4, 6 and 8 following wound dressing, 6 full-thickness skin samples were harvested from the wounds for histological observation and immunohistochemical detection of collagen and elastic fibers, and the wound healing time and healing rate were recorded. RESULTS: The prepared collagen sponge film was transparent and porous (50-300 microm in diameter) and allowed sustained PD release into normal saline within 48 h. Compared with the porcine skin, the composite material reduced exudation and maintained ideal moisture of the wound, and significantly shortened the wound healing time (P=0.000). On day 7, 14, and 21 following dressing, the composite material and porcine skin significantly increased the wound healing rate as compared with the negative control group (P=0.000), and on day 14, the composite achieved significantly greater healing rate than the porcine skin (P<0.05). CONCLUSION: HHK-collagen sponge-PHEMA/PD composite as a dressing material promotes burn wound healing in rats by allowing in vivo construction of tissue engineered epidermis. PHEMA is feasible for sustained drug delivery in this composite.

Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts.

Despite spontaneous sprouting of peripheral axons after transection injury, peripheral regeneration is incomplete and limited to short gaps, even with the use of autograft tissue, which is considered to be the "gold" standard. In an attempt to obviate some of the problems associated with autografts, including limited donor tissue and donor site morbidity, we aimed to synthesize a synthetic nerve guidance channel that would perform as well as the nerve autograft. Given that the patency of the nerve guidance channel is critical for repair, we investigated a series of nerve guidance channel designs where patency and the resulting regenerative capacity were compared in a transected rat sciatic nerve injury model. Three tube designs were compared to autograft tissue: plain, corrugated and coil-reinforced tubes of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate). Of the three designs, the coil-reinforced tubes demonstrated superior performance in terms of patency. By electrophysiology and histomorphometry, the coil-reinforced tubes demonstrated outcomes that were comparable to autografts after both 8 and 16 weeks of implantation. The nerve action potential (NAP) velocity and muscle action potential (MAP) velocity for the coil-reinforced PHEMA-MMA tube was 54.6+/-10.1 and 10.9+/-1.3 m/s, respectively at 16 weeks, which was statistically equivalent to those of the autograft at 37.5+/-7.9 and 11.3+/-2.0 m/s. The axon density in the coil-reinforced tube was 2.16+/-0.61x10(4) axons/mm2, which was statistically similar to that of the autograft of 2.41+/-0.62x10(4) axons/mm2 at 16 weeks. These coil-reinforced tubes demonstrated equivalence to autografts for nerve regeneration, demonstrating the importance of channel design to regenerative capacity and more specifically the impact of patency to regeneration.

Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection.

We have previously shown that a novel synthetic hydrogel channel composed of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (pHEMA-MMA) is biocompatible and supports axonal regeneration after spinal cord injury. Our goal was to improve the number and type of regenerated axons within the spinal cord through the addition of different matrices and growth factors incorporated within the lumen of the channel. After complete spinal cord transection at T8, pHEMA-MMA channels, having an elastic modulus of 263+/-13 kPa were implanted into adult Sprague Dawley rats. The channels were then filled with one of the following matrices: collagen, fibrin, Matrigel, methylcellulose, or smaller pHEMA-MMA tubes placed within a larger pHEMA-MMA channel (called tubes within channels, TWC). We also supplemented selected matrices (collagen and fibrin) with neurotrophic factors, fibroblast growth factor-1 (FGF-1) and neurotrophin-3 (NT-3). After channel implantation, fibrin glue was applied to the cord-channel interface, and a duraplasty was performed with an expanded polytetrafluoroethylene (ePTFE) membrane. Controls included animals that had either complete spinal cord transection and implantation of unfilled pHEMA-MMA channels or complete spinal cord transection. Regeneration was assessed by retrograde axonal tracing with Fluoro-Gold, and immunohistochemistry with NF-200 (for total axon counts) and calcitonin gene related peptide (CGRP, for sensory axon counts) after 8 weeks survival. Fibrin, Matrigel, methylcellulose, collagen with FGF-1, collagen with NT-3, fibrin with FGF-1, and fibrin with NT-3 increased the total axon density within the channel (ANOVA, p<0.05) compared to unfilled channel controls. Only fibrin with FGF-1 decreased the sensory axon density compared to unfilled channel controls (ANOVA, p<0.05). Fibrin promoted the greatest axonal regeneration from reticular neurons, and methylcellulose promoted the greatest regeneration from vestibular and red nucleus neurons. With Matrigel, there was no axonal regeneration from brainstem motor neurons. The addition of FGF-1 increased the axonal regeneration of vestibular neurons, and the addition of NT-3 decreased the total number of axons regenerating from brainstem neurons. The fibrin and TWC showed a consistent improvement in locomotor function at both 7 and 8 weeks. Thus, the present study shows that the presence and type of matrix contained within synthetic hydrogel guidance channels affects the quantity and origin of axons that regenerate after complete spinal cord transection, and can improve functional recovery. Determining the optimum matrices and growth factors for insertion into these guidance channels will improve regeneration of the injured spinal cord.

Restoration of enophthalmos in anophthalmic socket by HTR polymer.

A 2-year-old girl had undergone preoperative radiotherapy and enucleation without implantation for retinoblastoma in her right eye. She presented with supratarsal depression after secondary hydroxyapatite implantation. Computed tomography revealed insufficient right orbital volume, relative to left orbital volume. Injections of Bioplant hard tissue replacement synthetic bone filled the subperiosteal space of the orbital floor and lateral and medial wall for supratarsal augmentation. This had the desired effect: The filler lasted without sequela at least through 1.5 years of follow-up. Hard tissue replacement was also used to fill the remaining socket void and enhance the facial ridge width.

Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection.

Synthetic guidance channels or tubes have been shown to promote axonal regeneration within the spinal cord from brainstem motor nuclei with the inclusion of agents such as matrices, cells, or growth factors to the tube. We examined the biocompatibility and regenerative capacity of synthetic hydrogel tubular devices that were composed of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA). Two PHEMA-MMA channels, having a mean elastic modulus of either 177 or 311 kPa were implanted into T8-transected spinal cords of adult Sprague Dawley rats. The cord stumps were inserted into the channels and fibrin glue was applied to the cord-channel interface. An expanded polytetrafluoroethylene (ePTFE) membrane was used for duraplasty. Controls underwent cord transection alone. Gross and microscopic examination of the spinal cords showed continuity of tissue within the synthetic guidance channels between the cord stumps at 4 and 8 weeks. There was a trend towards an increased area and width of bridging neural tissue in the 311-kPa guidance channels compared to the 177-kPa channels. Neurofilament stained axons were visualized within the bridging tissue, and serotonergic axons were found to enter the 311-kPa channel. Retrograde axonal tracing revealed regeneration of axons from reticular, vestibular, and raphe brainstem motor nuclei. For both channels, there was minimal scarring at the channel-cord interface, and less scarring at the channel-dura interface compared to that observed next to the ePTFE. The present study is the first to show that axons from brainstem motor nuclei regenerated in unfilled synthetic hydrogel guidance channels after complete spinal cord transection.

La evolución de la adhesion a dentina / The history in dentinal adhesion

Se realiza una revisión a la historia de la adhesión comenzando en las culturas precolombinas ("era pre-adhesiva"), para continuar en la "era adhesiva" con las aportaciones de Buonocuore y la aparición del Bis-GMA, pasando por la incorporación al mercado dental de los fosfatos, los oxalatos, el sistema Gluma. Se analiza también la descripción de la capa híbrida por Nakabayashi, después aparecen los primeros acuosos y la hibridación de tejidos duros hasta llegar a los sistemas adhesivos autograbadores (AU)

An overview of dentin bonding history is done by the author since early south American cultures (pre-adhesive age) to continued in the adhesive age with Buonoccore's findings and the rise of Bis-GMA and the first dentin adhesives based on phosphate, oxalate and Gluma system. Nakabayashi's hybrid layer is described and the evolution of aqueous primers and hard tissues hybridation until arrival of newest self-etching adhesives (AU)