Semirational engineering of Cytophaga hutchinsonii polyphosphate kinase for developing a cost-effective, robust, and efficient adenosine 5'-triphosphate regeneration system.

IMPORTANCE: The adenosine 5'-triphosphate (ATP) regeneration system can significantly reduce the cost of many biocatalytic processes. Numerous studies have endeavored to utilize the ATP regeneration system based on Cytophaga hutchinsonii PPK (ChPPK). However, the wild-type ChPPK enzyme possesses limitations such as low enzymatic activity, poor stability, and limited substrate tolerance, impeding its application in catalytic reactions. To enhance the performance of ChPPK, we employed a semi-rational design approach to obtain the variant ChPPK/A79G/S106C/I108F/L285P. The enzymatic kinetic parameters and the catalytic performance in the synthesis of nicotinamide mononucleotide demonstrated that the variant ChPPK/A79G/S106C/I108F/L285P exhibited superior enzymatic properties than the wild-type enzyme. All data indicated that our engineered ATP regeneration system holds inherent potential for implementation in biocatalytic processes.

Navigating the kidney organoid: insights into assessment and enhancement of nephron function.

Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care.NEW & NOTEWORTHY Kidney organoids are three-dimensional structures derived from stem cells, mimicking the major components of mammalian kidneys. Although they show great promise, their functional capacity has become a critical question. This review explores the advancements and challenges in evaluating and enhancing kidney organoid function, including the use of organ-on-chip technologies, multiomics data, and in vivo transplantation. Integrating these approaches to further enhance their physiological relevance will continue to advance disease modeling and regenerative medicine applications.

Association Between Urban Regeneration and Healthcare-Seeking Behavior of Affected Residents: A Natural Experiment in two Multi-Ethnic Deprived Housing Areas in Denmark.

Area regeneration of deprived neighborhoods is being used to reduce health inequality, socioeconomic deprivation and ethnic segregation. This quasi-experimental study examines if long-term graded exposure to urban regeneration is associated with primary healthcare-seeking behavior among residents. We compared general practitioner (GP) contacts from 2015-2020 in two adjacent, deprived social housing areas, one exposed to area regeneration. Populations were into Western and non-Western males and females aged 15 years and older (N = 3,960). Mean annual GP contact frequency for each group were estimated and a difference-in-difference (DiD) analysis was conducted with adjustments for propensity scores based on baseline characteristics. GP contact frequency increased for all groups across time with a systematically higher level and faster increase in the control groups. In particular, the mean difference between the exposed and control area for Western women increased from -4.67 to -5.76 annual contacts across the period. The mean differences in contact frequency increased for all groups but results of the DiD analyses were insignificant. In conclusion, an increasing gap in GP contact frequency, with the highest levels in the control area, was observed for all comparisons across time. More long-term research is needed to understand how the increasing gaps evolve.

Ploidy Status, Nuclear DNA Content and Start Codon Targeted (SCoT) Genetic Homogeneity Assessment in Digitalis purpurea L., Regenerated In Vitro.

Digitalis purpurea L. is a therapeutically important plant that synthesizes important cardiotonics such as digitoxin and digoxin. The present work reports a detailed and efficient propagation protocol for D. purpurea by optimizing various PGR concentrations in Murashige and Skoog (MS) medium. The genetic homogeneity of in vitro regenerants was assessed by the flow cytometric method (FCM) and Start Codon Targeted (SCoT) marker technique. Firstly, the seeds inoculated in full MS medium added with 0.5 mg/L GA3 produced seedlings. Different parts such as hypocotyl, nodes, leaves and apical shoots were used as explants. The compact calli were obtained on BAP alone or in combinations with 2, 4-D/NAA. The hypocotyl-derived callus induced somatic embryos which proliferated and germinated best in 0.75 mg/L BAP-fortified MS medium. Scanning electron microscopic (SEM) images confirmed the presence of various developmental stages of somatic embryos. Shoot regeneration was obtained in which BAP at 1.0 mg/L and 2.0 mg/L BAP + 0.5 mg/L 2,4-D proved to be the best treatments of PGRs in inducing direct and indirect shoot buds. The regenerated shoots showed the highest rooting percentage (87.5%) with 24.7 ± 1.9 numbers of roots/shoot in 1.0 mg/L IBA augmented medium. The rooted plantlets were acclimatized in a greenhouse at a survival rate of 85-90%. The genome size and the 2C nuclear DNA content of field-grown, somatic embryo-regenerated and organogenic-derived plants were estimated and noted to be 3.1, 3.2 and 3.0 picogram (pg), respectively; there is no alteration in ploidy status and the DNA content, validating genetic uniformity. Six SCoT primers unveiled 94.3%-95.13% monomorphic bands across all the plant samples analyzed, further indicating genetic stability among in vitro clones and mother plants. This study describes for the first time successful induction of somatic embryos from hypocotyl callus; and flow cytometry and SCoT marker confirmed the genetic homogeneity of regenerated plants.

Regenerative Approaches for Chronic Wounds.

Chronic skin wounds are commonly found in older individuals who have impaired circulation due to diabetes or are immobilized due to physical disability. Chronic wounds pose a severe burden to the health-care system and are likely to become increasingly prevalent in aging populations. Various treatment approaches exist to help the healing process, although the healed tissue does not generally recapitulate intact skin but rather forms a scar that has inferior mechanical properties and that lacks appendages such as hair or sweat glands. This article describes new experimental avenues for attempting to improve the regenerative response of skin using biophysical techniques as well as biochemical methods, in some cases by trying to harness the potential of stem cells, either endogenous to the host or provided exogenously, to regenerate the skin. These approaches primarily address the local wound environment and should likely be combined with other modalities to address regional and systemic disease, as well as social determinants of health.

Direct somatic embryogenesis and flow cytometric assessment of ploidy stability in regenerants of Caladium × hortulanum 'Fancy'.

Caladium × hortulanum 'Fancy' is an important ornamental plant grown in pots and landscapes and known for its colorful leaves often used for interior decorations. In this work, we present a method of in vitro regeneration from three explants source through direct somatic embryogenesis (DSE) wherein the regenerated plants were screened for ploidy changes through flow cytometry analysis. Tuber, leaf and petiole explants were cultured on MS basal medium supplemented with 1-napthalene acetic acid (NAA), 6-benzyl amino purine (BAP) and N-phenyl-N'-1, 2,3-thiadiazol-5-ylurea (TDZ) concentrations. Tuber explants induced highest direct somatic embryos on NAA (1 mg L- 1) + BAP (0.5 mg L- 1) with 55.6 mean number of embryos per explant while as leaf and petiole explants amended with 1 mg L- 1 TDZ developed 18.7 and 12.27 mean number of embryos per explant respectively. The highest embryo conversion frequency was achieved on BAP (2 mg L- 1) + NAA (0.2 mg L- 1) with 44.2, 18.7 and 7.5 mean number of plantlets produced per tuber, leaf and petiole explant respectively after 4 weeks of culture. Plantlets were later rooted and maximum number of roots (6.33) per shoot was achieved on 2 mg L- 1 indolebutyric acid amended medium. Description of the process of DSE is presented through the histological and SEM evidences. The 2C DNA content of field grown plants and the DSE regenerants evaluated under flow cytometric analysis were 8.06 pg and 8.28 pg respectively showing no ploidy changes. Hence, a successful protocol of inducing direct somatic embryos from three explant types with efficient embryo conversion frequency was obtained with regenerants showing similar DNA ploidy as that of their parent plants.

Comparative study of heat transfer and thermal damage assessment models for hyperthermia treatment.

Appropriate heating of the tumor can ablate tumor cells with minimal damage to healthy tissue and low side effects to the patient. Therefore, it is important to estimate power dissipation requirement and predict thermal damage in tumor before hyperthermia treatment. This work applied a mathematical model on heat transfer in two-layered spherical tissue to predict the temperature profile within hyperthermia domain. The present bioheat transfer problem was analyzed based on the Pennes equation, the thermal wave and dual-phase lag modes in order to explore the effect of analysis mode on the power dissipation requirement. The Arrenius equation, the modified thermal damage model with regeneration term, and the equivalent thermal dose equation were used to evaluate the thermal damage and discuss their effects on thermal damage prediction. The computation results show that the model of bioheat transfer and the non-Fourier effect significantly affects the power dissipation requirement. The damage parameter value predicted by the modified thermal damage model with regeneration term seems to have a limit value of Ω = 1. The results imply that the regeneration of biological tissue can prevent the tissue from thermal damage, the equivalent thermal dose equation is more related to heating time, and the Arrenius equation is more related to heating temperature.

Single Myofiber Culture Assay for the Assessment of Adult Muscle Stem Cell Functionality Ex Vivo.

Adult skeletal muscle tissue harbors a stem cell population that is indispensable for its ability to regenerate. Upon muscle damage, muscle stem cells leave their quiescent state and activate the myogenic program ultimately leading to the repair of damaged tissue concomitant with the replenishment of the muscle stem cell pool. Various factors influence muscle stem cell activity, among them intrinsic stimuli but also signals from the direct muscle stem cell environment, the stem cell niche. The isolation and culture of single myofibers with their associated muscle stem cells preserves most of the interaction of the stem cell with its niche and is, therefore, the closest possibility to study muscle stem cell functionality ex vivo. Here, a protocol for the isolation, culture, siRNA transfection and immunostaining of muscle stem cells on their respective myofibers from mouse EDL (extensor digitorum longus) muscles is provided. The experimental conditions outlined here allow the study and manipulation of muscle stem cells ex vivo including investigation of myogenic activity without the inherent need for in vivo animal experiments.

The loss of regeneration competency in the animal kingdom at the expense of immunity: A journey in retrospect.

Regeneration refers to the structural growth of damaged organs or tissues and their functional integration into the existing system. Injury induced regenerative response is extremely variable across the animal kingdom. On one hand the early acoelomates can reform the entire animal even from dissociated cells, on the other; the capacity in humans is mostly restricted to wound healing. A general trend of regenerative ability is the existence of an inverse relationship between the robustness of immune system and the degree of regeneration throughout the animal kingdom. This review summarizes the evolutionary advancement of immune system in different groups and gives an account of their respective regenerative competency.

Effects of an urban regeneration program on related social determinants of health in Chile: A pre-post intervention study.

Urban regeneration programs, such as "Programa Quiero mi Barrio" (PQMB) that is carried out in neighborhoods with greater deprivation across Chile, can improve health and quality of life in socio-economically deprived neighborhoods. The aim of this study was to analyze the effects of this program on the physical, social, and safety environments of neighborhoods intervened between 2011 and 2018, according to gender and socioeconomic position. Four indices and six sub-indices were constructed to measure physical, social, and safety environments of the neighborhoods. We conducted a pre- and post-intervention analysis with 2095 people using linear models adjusted for repeated measurements. After the intervention, participants had an improved perception of physical, social, and safety environments, as well as the use of spaces, particularly among women and people with higher levels of education. Therefore, the PQMB program is a form of public policy that can improve the quality of life and health of people living in underprivileged areas.

Mass propagation through direct and indirect organogenesis in three species of genus Zephyranthes and ploidy assessment of regenerants through flow cytometry.

Genus Zephyranthes consists of economically important plant species due to their high ornamental value and presence of valuable bioactive compounds. However, this genus propagates by asexual division only which gives slow propagation rate. Plant tissue culture has the potential to provide efficient techniques for rapid multiplication and genetic improvement of the genus. In this work, a dual in vitro regeneration system through callus mediated shoot regeneration and direct shoot regeneration in species Zephyranthes candida, Zephyranthes grandiflora and Zephyranthes citrina was investigated. Bulb, leaf and root explants were cultured on Murashige and Skoog (MS) medium amended with different plant growth regulators (PGR's) viz. 2,4-dichlorophenoxyacetic acid (2,4-D), 1-Naphthalene acetic acid (NAA), 6-benzyl amino purine (BAP), N-phenyl-N'-1,2,3 -thiadiazol-5-ylurea (TDZ), 6-Furfuryl- aminopurine (KIN) alone or in combinations for callus induction and regeneration. Only bulb explants showed callus induction and regeneration response on different PGR combinations with a varied response in callus induction percentage, callus color and callus texture. Creamish compact callus (CC) was induced on 2 mg L[Formula: see text] 2,4-D, brown friable callus (BF) on 2 mg L[Formula: see text] NAA + 1 mg L[Formula: see text] BAP and green friable callus (GF) callus on 1 mg L[Formula: see text] KIN + 3 mg L[Formula: see text] NAA. The maximum shoot multiplication from different callus types (indirect organogenesis) was achieved on 2 mg L[Formula: see text] BAP alone without combinations. Bulb explants of Z. grandiflora induced maximum callus induction percentage (86.4%) and shoot regeneration percentage (83.5%) with the maximum 08 shoots per 150 mg callus mass. The induction and regeneration response was followed in the order of Z. grandiflora > Z. candida > Z. citrina. Similarly, maximum direct organogenesis from bulb explants was obtained in Z. grandiflora (93.3%) followed by Z. candida (91.5%) and Z. citrina (90.4%) on 3 mg L[Formula: see text] TDZ amended MS media. Adventitious root induction was achieved on 2 mg L[Formula: see text] IBA with a maximum of 8 roots per shoot. The in vitro raised plantlets were successfully acclimatized in the field with 85% survival efficiency. The genome size (2C DNA content) of the field-grown plants and in vitro regenerated plants, evaluated through flow cytometry technique, were similar and showed no ploidy changes. An efficient mass propagation protocol was established for obtaining plants with unaltered genome size in the three species of Zephyranthes.

Cardiac MRI Assessment of Mouse Myocardial Infarction and Regeneration.

Small animal models are indispensable for cardiac regeneration research. Studies in mouse and rat models have provided important insights into the etiology and mechanisms of cardiovascular diseases and accelerated the development of therapeutic strategies. It is vitally important to be able to evaluate the therapeutic efficacy and have reliable surrogate markers for therapeutic development for cardiac regeneration research. Magnetic resonance imaging (MRI), a versatile and noninvasive imaging modality with excellent penetration depth, tissue coverage, and soft-tissue contrast, is becoming a more important tool in both clinical settings and research arenas. Cardiac MRI (CMR) is versatile, noninvasive, and capable of measuring many different aspects of cardiac functions, and, thus, is ideally suited to evaluate therapeutic efficacy for cardiac regeneration. CMR applications include assessment of cardiac anatomy, regional wall motion, myocardial perfusion, myocardial viability, cardiac function assessment, assessment of myocardial infarction, and myocardial injury. Myocardial infarction models in mice are commonly used model systems for cardiac regeneration research. In this chapter, we discuss various CMR applications to evaluate cardiac functions and inflammation after myocardial infarction.

An Increase in Medial Joint Space Width After Medial Open-Wedge High Tibial Osteotomy Is Associated With an Increase in the Postoperative Weight-Bearing Line Ratio Rather Than With Cartilage Regeneration: Comparative Analysis of Patients Who Underwent Second-Look Arthroscopic Assessment.

PURPOSE: To investigate relevant factors influencing increases in medial joint space width (JSW) after medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Between January 2010 and December 2018, the electronic medical records of consecutive patients who underwent MOWHTO and subsequent second-look arthroscopic assessment at least 12 months after MOWHTO were retrospectively evaluated. The patients were classified into 2 groups according to changes in the medial JSW of the knee at the time of the second-look operation compared with that at baseline before the initial surgical procedure. Various radiographic parameters, arthroscopic findings, and clinical scores were compared between the groups, and regression analysis was performed to identify factors related to increases in medial JSW. RESULTS: A total of 114 patients were analyzed. In a bivariate analysis, patients who experienced an increase in medial JSW showed a significantly higher postoperative weight-bearing line ratio (WBLR) (P = .008) and a greater proportion of severe preoperative cartilage lesions in the medial compartment of the knee compared with patients with a maintained or reduced medial JSW (P = .035). In terms of clinical scores, patients with an increased medial JSW showed relatively favorable clinical outcomes at the time of the second-look operation. Regression analysis indicated only postoperative WBLR as a relevant factor associated with an increase in medial JSW after MOWHTO (odds ratio, 1.057; P = .01). Additional analysis with patients reclassified according to the postoperative WBLR showed that as the postoperative WBLR increased, the medial JSW increased, without a significant change in the lateral JSW. CONCLUSIONS: An increase in the medial JSW of the knee joint after MOWHTO appears to be associated with an increase in the postoperative WBLR, not with cartilage regeneration. Obtaining adequate correction so that the postoperative WBLR is within 60% to 70% would be desirable in terms of postoperative changes in the medial JSW, as well as clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

A Rabbit Femoral Condyle Defect Model for Assessment of Osteochondral Tissue Regeneration.

Osteochondral tissue repair represents a common clinical need, with multiple approaches in tissue engineering and regenerative medicine being investigated for the repair of defects of articular cartilage and subchondral bone. A full thickness rabbit femoral condyle defect is a clinically relevant model of an articulating and load bearing joint surface for the investigation of osteochondral tissue repair by various cell-, biomolecule-, and biomaterial-based implants. In this protocol, we describe the methodology and 1.5- to 2-h surgical procedure for the generation of a reproducible, full thickness defect for construct implantation in the rabbit medial femoral condyle. Furthermore, we describe a step-by-step procedure for osteochondral tissue collection and the assessment of tissue formation using standardized histological, radiological, mechanical, and biochemical analytical techniques. This protocol illustrates the critical steps for reproducibility and minimally invasive surgery as well as applications to evaluate the efficacy of cartilage and bone tissue engineering implants, with emphasis on the usage of histological and radiological measures of tissue growth. Impact statement Although multiple surgical techniques have been developed for the treatment of osteochondral defects, repairing the tissues to their original state remains an unmet need. Such limitations have thus prompted the development of various constructs for osteochondral tissue regeneration. An in vivo model that is both clinically relevant and economically practical is necessary to evaluate the efficacy of different tissue engineered constructs. In this article, we present a full thickness rabbit femoral condyle defect model and describe the analytical techniques to assess the regeneration of osteochondral tissue.

Inotropic assessment in engineered 3D cardiac tissues using human induced pluripotent stem cell-derived cardiomyocytes in the BiowireTM II platform.

To develop therapeutics for cardiovascular disease, especially heart failure, translational models for assessing cardiac contractility are necessary for preclinical target validation and lead optimization. The availability of stem cell-derived cardiomyocytes (SC-CM) has generated a great opportunity in developing new in-vitro models for assessing cardiac contractility. However, the immature phenotype of SC-CM is a well-recognized limitation in inotropic evaluation, especially regarding the lack of or diminished positive inotropic response to ß-adrenergic agonists. Recent development of 3D engineered cardiac tissues (ECTs) using human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CM) in the BiowireTM II platform has shown improved maturation. To evaluate their suitability to detect drug-induced changes in cardiac contractility, positive inotropes with diverse mechanisms, including ß-adrenergic agonists, PDE3 inhibitors, Ca2+-sensitizers, myosin and troponin activators, and an apelin receptor agonist, were tested blindly. A total of 8 compounds were evaluated, including dobutamine, milrinone, pimobendan, levosimendan, omecamtiv mecarbil, AMG1, AMG2, and pyr-apelin-13. Contractility was evaluated by analyzing the amplitude, velocity and duration of contraction and relaxation. All tested agents, except pyr-apelin-13, increased contractility by increasing the amplitude of contraction and velocity. In addition, myosin and troponin activators increase contraction duration. These results indicate that ECTs generated in the BiowireTM II platform can identify inotropes with different mechanisms and provides a human-based in-vitro model for evaluating potential therapeutics.

Measuring the Costs of Limb Regeneration and Their Transgenerational Consequences in Two Nearctic Lady Beetles (Coleoptera: Coccinellidae).

We examined the ability of Coleomegilla maculata DeGeer and Hippodamia convergens Guerin-Meneville to regenerate, during pupation, a foreleg amputated in the fourth instar. Leg regeneration was complete for 80.7% of amputated H. convergens larvae, with 12.5% regenerating partially, and 6.8% showing no regeneration. Regeneration in C. maculata was 72.2% complete, 20.5% partial, and 7.2% none, but mortality following ablation was slightly higher than for H. convergens (7.4 vs. 0.6%). Ablation/regeneration caused a slight delay in pupation, but pupation time, fresh mass at emergence, and reproductive performance remained unaffected in either species. Reciprocal crosses were made between regenerated and unoperated beetles, and 12 progeny reared from the second clutch of each female in all treatments. Mating treatment affected eclosion time in H. convergens, whereas in C. maculata, larval development and pupation time were also affected. Considering all treatments, larval mortality was higher in H. convergens than in C. maculata, but lower when both H. convergens parents regenerated. Parental mating treatment did not affect adult weight in either species, but development of C. maculata progeny was faster when only the sire regenerated, and slower when the only the dame regenerated, whereas progeny of regenerated sires completed pupated faster than those sired by controls. We infer that genes activated during regeneration have pleiotropic effects with subtle, gender-specific, epigenetic consequences. If these pleiotropic effects are genetically linked to important traits, regenerative genetic elements could be conserved in coccinellids via natural selection acting on these traits, rather than on regenerative ability per se.

The movement dynamics of autotomized lizards and their tails reveal functional costs of caudal autotomy.

Autotomy has evolved independently several times in different animal lineages. It frequently involves immediate functional costs, so regeneration evolved in many instances to restore the functionality of that body part. Caudal autotomy is a widespread antipredator strategy in lizards, although it may affect energy storage, locomotion dynamics, or survival in future encounters with predators. Here, we assessed the effect of tail loss on the locomotor performance of wall lizards (Podarcis muralis), as well as the recovery of locomotor functionality of lizards with regenerated tails, and the movement dynamics of shed tails that were either intact or having regenerated portions. Tail loss had no effect on locomotion over unhindered spaces, possibly due to compensation between a negative effect on the stride of front limbs, and a positive effect of losing mass and friction force. We found a clear negative impact of tail loss on locomotion in spaces with interspersed obstacles, in which tailed lizards jumped larger distances when leaving the obstacles. Besides, lizards that used the tail to push off the ground were able to approach the obstacles from further, so that the tail seemed to be useful when used during jumping. Regeneration fully restores lizard's locomotor capacities, but tail antipredator value, as indicated by the intensity of post-autotomic movements, is only partially retrieved. From these results, we propose that, together with the recovery of post-autotomy antipredator capacities, the restoration of the organismal locomotor performance may have been an important, yet frequently neglected factor in the evolution of lizard's regeneration ability.

Periodontal regeneration versus extraction and dental implant or prosthetic replacement of teeth severely compromised by attachment loss to the apex: A randomized controlled clinical trial reporting 10-year outcomes, survival analysis and mean cumulative cost of recurrence.

BACKGROUND: Periodontal regeneration can change tooth prognosis and represents an alternative to extraction in teeth compromised by severe intra-bony defects. The aim of this study was to compare periodontal regeneration (PR) with tooth extraction and replacement (TER) in a population with attachment loss to or beyond the apex of the root in terms of professional, patient-reported and economic outcomes. METHODS: This was a 10-year randomized controlled clinical trial. 50 stage III or stage IV periodontitis subjects with a severely compromised tooth with attachment loss to or beyond the apex were randomized to PR or TER with either an implant- or a tooth-supported fixed partial denture. Subjects were kept on a strict periodontal supportive care regimen every 3 months and examined yearly. Survival and recurrence analysis were performed. RESULTS: 88% and 100% survival rates were observed in the PR and TER groups. Complication-free survival was not significantly different: 6.7-9.1 years for PR and 7.3-9.1 years for TER (p = .788). In PR, the observed 10-year attachment gain was 7.3 ± 2.3 mm and the residual probing depths were 3.4 ± 0.8 mm. Recurrence analysis showed that the 95% confidence interval of the costs was significantly lower for PR compared with TER throughout the whole 10-year period. Patient-reported outcomes and oral health-related quality-of-life measurements improved in both groups. CONCLUSIONS: Periodontal regeneration can change the prognosis of hopeless teeth and is a less costly alternative to tooth extraction and replacement. The complexity of the treatment limits widespread application to the most complex cases but provides powerful proof of principle for the benefits of PR in deep intra-bony defect.

Histological assessment of human regenerative endodontic procedures (REP) of immature permanent teeth with necrotic pulp/apical periodontitis: A systematic review.

The aim of this study was to systematically review the histological evidence of the neo-formed tissues inside the root canals of human teeth having previously received regenerative endodontic treatment. An electronic research was performed in the MEDLINE, Web of Science, Scopus and Cochrane Library databases using controlled vocabulary. The retrieved studies were screened by two reviewers according to the predetermined inclusion and extrusion criteria and were full-text-evaluated. Research resulted in 160 studies. Among them, twelve fitted the inclusion criteria and were critically appraised. The tissues formed in the root canals of immature human teeth treated with REP indicate repair or a combination of repair and regeneration. Pulp remnants and healthy periapical tissues seem to improve regeneration. The level of available evidence was low. Further clinical studies are needed in order to establish the appropriate treatment protocol related to the pretreatment status of the dental pulp and the periapical tissues.