Augmenting osteoporotic bone regeneration through a hydrogel-based rejuvenating microenvironment.

Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period. To address this issue, this study introduces a hydrogel that creates a rejuvenating microenvironment, thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery. The hydrogel, named GelHFS, was created through host-guest polymerization of gelatin and acrylated ß-cyclodextrin. Incorporation of the human fetal mesenchymal stem cell secretome (HFS) formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche. Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrin ß1-induced focal adhesion pathway. Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrin ß1-expressing cells and enhanced new bone formation and bone strength. Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect. These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.

The Rejuvenation Effect of Bio-Oils on Long-Term Aged Asphalt.

Generally, rejuvenators are used to supply missing components of aged asphalt, reverse the aging process, and are widely used in asphalt maintenance and recycling. However, compared with traditional rejuvenators, bio-oil rejuvenators are environmentally friendly, economical and efficient. This study looks into the effect of the three different bio-oils, namely sunflower oil, soybean oil, and palm oil, on the physical properties, rheological properties and chemical components of aged asphalt at different dosages. The asphalt physical properties and Dynamic Shear Rheological (DSR) test results show that with the increase in bio-oil, the physical properties and rheological properties of rejuvenated asphalt are close to those of virgin asphalt, but the high-temperature rutting resistance needs to be further improved. The results of Fourier Transform Infrared Spectroscopy (FTIR) show that the carbonyl and sulfoxide indices of rejuvenated asphalt are much lower than those of aged asphalt. Moreover, the rejuvenation efficiency of aged asphalt mixed with sunflower oil is better than that with soybean oil and palm oil at the same dosage.

Relationships of GDF8 and 11 and Their Antagonists With Decline of Grip Strength Among Older Adults in the Baltimore Longitudinal Study of Aging.

Although growth/differentiation factor 11 (GDF11), growth/differentiation factor 8 (GDF8), and their circulating antagonists, which include GDF11 and GDF8 propeptides, follistatin (FST), WAP, Follistatin/Kazal, Immunoglobulin, Kunitz And Netrin Domain Containing (WFIKKN)1, and WFIKKN2, have been shown to influence skeletal muscle and aging in mice, the relationship of these circulating factors with human phenotypes is less clear. This study aimed to characterize the relationship between plasma GDF8, GDF11, FST, WFIKKN1, and WFIKKN2 concentrations with the decline of grip strength in 534 adults, ≥65 years, who participated in the Baltimore Longitudinal Study of Aging and had grip strength measured over time. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST (isoform FST315 and cleaved form FST303), WFIKKN1, and WFIKKN2 concentrations were measured using selected reaction monitoring-tandem mass spectrometry at baseline. Grip strength was measured at baseline and at follow-up visits (median follow-up 8.87 years). Mean (standard deviation) grip strength declined in men and women by -0.84 (2.45) and -0.60 (1.32) kg/year, respectively. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST315, FST303, WFIKKN1, and WFIKKN2 concentrations were not independently predictive of the decline of grip strength in men or women in multivariable linear regression analyses that adjusted for potential confounders. In conclusion, circulating GDF8, GDF11, and their antagonists do not appear to influence the decline of grip strength in older men or women.

Rejuvenating the aging upper periorbita.

PURPOSE: To investigate the efficacy of a comprehensive surgical approach in rejuvenating the aging upper periorbita. METHODS: Three hundred and twenty eyes of 160 patients who were treated for dermatochalasis(D), eyebrow ptosis (EP) and blepharoptosis (BP) were included in the study. One hundred and ninety-eight patients had only dermatochalasis, 74 patients had D and EP, 39 patients had D and BP, 7 patients had D, EP and BP and 2 patients had D, EP and blepharospasm. The patients were evaluated before surgery, at 1 week, 1 month and 6 months after surgery. Dermatochalasis was scored between 0 and 3 points according to upper lid laxity and IP drooping. EP was scored between 0 and 2 points as normal, lateral EP and total EP. Aging was classified as mild in those with a total score of less than 3 points, moderate in those with a score of 3-6 and severe in those above 6 points. RESULTS: Of the patients, 121 were female and 39 were male, with a mean age of 52 (40-87) years. The surgeries were performed as follows: upper eyelid blepharoplasty (UEB) 197(61.6%) patients, UEB + browpexy(B) 77(24.1%) patients, UEB + B + levator resection(LR) 7(2.2%) and UEB + LR 39 (12.2%) patients. While a statistically significant improvement was observed in patients who underwent UEB + B (p < 0.001), postoperative improvements were not found statistically significant compared to preoperative scores in other surgeries. The postsurgical scores showed statistically significant improvement in all age groups (p < 0.001). CONCLUSIONS: A comprehensive surgical treatment can provide effective results in upper periorbital rejuvenation for patients with varying degrees of upper periorbital aging.

In Vitro, In Vivo, and In Silico Analyses of Molecular Anti-Pigmentation Mechanisms of Selected Thai Rejuvenating Remedy and Bioactive Metabolites.

Thai rejuvenating remedies are mixed herbal formulas promoting longevity. Due to the complexity, the biological activities of these remedies are minimal. Therefore, in this study, the authors evaluated the anti-pigmentation effect at the molecular level of the selected Thai rejuvenating remedy to fulfill the knowledge gap. First, the authors found that the selected remedy showed promising activity against the tyrosinase enzyme with an IC50 value of 9.41 µg/mL. In the comparison, kojic acid (positive control) exhibited an IC50 value of 3.92 µg/mL against the same enzyme. Later, the authors identified glabridin as a bioactive molecule against tyrosinase with an IC50 value of 0.08 µg/mL. However, ethyl p-methoxycinnamate was the most abundant metabolite found in the remedy. The authors also found that the selected remedy and glabridin reduced the melanin content in the cell-based assay (B16F1) but not in the zebrafish larvae experiment. Finally, the authors conducted a computational investigation through molecular docking proposing a theoretical molecular interplay between glabridin, ethyl p-methoxycinnamate, and target proteins (tyrosinase and melanocortin-1 receptor, MC1R). Hence, in this study, the authors reported the molecular anti-pigmentation mechanism of the selected Thai rejuvenating remedy for the first time by combining the results from in silico, in vitro, and in vivo experiments.

Growth differentiation factor 11: A proangiogenic drug as a potential antiaging regulating molecule.

Organs and tissues are subjected to numerous alterations during aging, as a result of complex biochemical changes. Aging is certainly associated with the accumulation of "antiaging" and "proaging" factors in the systemic circulation. The effects of young blood on rejuvenation of regenerative capacity suggest the existence of multiple "proyouthful" factors, such as growth differentiation factor 11 (GDF11), in the young blood of animals. GDF11 is a member of the transforming growth factor beta (TGFß) superfamily of cytokines, and appears to be a critical rejuvenation factor in aging organs. In the context of aging, GDF11 promotes vascular and neural plasticity of the central nervous system. Parabiosis, the surgical linking of circulations between old and young mice, was employed to identify GDF11 as an antihypertrophic factor that appears to rejuvenate the aging murine heart. Current theories suggest that GDF11 in young blood has beneficial effects on cognitive and cardiovascular functions and wound healing. The cellular mechanisms of GDF11 in cardiovascular, neurological, skin and skeletal muscle diseases are not clearly defined, but evidence indicates that it may function as a proneurogenic and proangiogenic drug. GDF11 binds and activates specific receptor complexes, which transmit signals by two procedures: the TGFß-Smad pathway and the bone morphogenic protein (BMP)-Smad pathway. GDF11 is perhaps only the first in a series of circulating molecules that will be found to influence the aging of different tissues, and it may be a potential candidate for therapeutic intervention against angiogenesis-related disorders.

The long and winding road: homeostatic and disordered haematopoietic microenvironmental niches: a narrative review.

Haematopoietic microenvironmental niches have been described as the 'gatekeepers' for the blood and immune systems. These niches change during ontogeny, with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state conditions. To determine the structure and function of different haematopoietic microenvironmental niches, it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning. A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell niches. The latter is reported to include endothelial cells and mesenchymal stromal cells (MSCs), skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations, which form crucial components of these microenvironments under homeostatic conditions. Dysregulation or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process. A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research review. In the context of haematopoiesis, clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants, the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019 (COVID-19) infections, and, given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing, the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this knowledge for rejuvenating the age-compromised bone marrow haematopoietic niches and restoring haematopoiesis.

Rejuvenating the human gut microbiome.

Industrial advances have caused significant loss of diversity in our gut microbiome, potentially increasing our susceptibility to many diseases. Recently, rewilding the human gut microbiome - that is, bringing it back to an ancestral or preindustrial state (e.g., by transplanting stool material from donors in nonindustrial societies) - has been hotly debated from medical, ethical, and evolutionary perspectives. Here we propose an alternative solution: rejuvenating the human gut microbiome by stool banking and autologous fecal microbiota transplantation, that is, collecting the hosts' stool samples at a younger age when they are at optimal health, and cryopreserving the samples in a stool bank for the hosts' own future use. In this article we discuss the motivation, applications, feasibility, and challenges of this solution.

Evaluation of the effect of age of the younger mice on the rejuvenation of the older mice by heterochronic parabiosis.

Heterochronic parabiosis is used to study the systemic effects of aging and involves surgically connecting two animals of different ages such that they have common blood circulation. Although this technique has been prevalent for a long time, there is no scientific consensus on the age of the animals that should be used. We hypothesized that the younger the animal, the greater would be its rejuvenating effect. Hence, to test this hypothesis, we created parabiosis of 67-week-old mice with younger mice of different ages (4-week-old and 8-week-old). We evaluated the changes in appearance and the expression IL-1A, IL-6, and Cdkn2a (p16) in the liver, kidney, brain, and skin. These cytokines belong to the senescence-associated secretory phenotype (SASP) factors, and are indicators of aging. Although we did not find any significant changes in the appearance of the mice, we found statistically significant differences in some SASP factors between the liver of the 4-week-old and 8-week-old pairs. However, overall, compared to the 8-week-old mice, the 4-week-old does not exert a significantly higher rejuvenation effect on the older mice. Hence, we concluded that the rejuvenation of older mice during heterochronic parabiosis might not be affected by the exact age of the younger mice.

A new approach to regenerative medicine in gynecology.

OBJECTIVE: To evaluate the efficacy of the injection of microfragmented adipose tissue in the treatment of women with genitourinary syndrome of menopause (GSM). METHODS: This observational cohort study included 12 women who received one session of multiple injections of microfragmented adipose tissue using the SEFFIGYN™ medical device. Symptoms such as burning, itching, dryness, pain on penetration, pain during deep intercourse, and pain on urination were assessed before the patient's treatment (T0), after 15 days (T15), and after 5 months (5Mo) using the Numerical Rating Scale (NRS). RESULTS: An improvement of vulvar trophism was clinically evident already 2 weeks after treatment; all symptoms were notably attenuated compared with the initial visit, as demonstrated by statistically significant reductions of the NRS scores (P = 0.003 for itching, P = 0.008 for pain on urination, and P < 0.001 for the other symptoms, Sign test). Moreover, all symptoms continued to improve over time. All patients reported a positive change in their quality of life and a resumption of sexual life. CONCLUSION: The use of microfragmented adipose tissue in GSM is promising. Nevertheless, more studies will be fundamental to exclude a potential placebo effect and better understand the underlying molecular mechanism of action.

Age-Related Changes in the Inflammatory Status of Human Mesenchymal Stem Cells: Implications for Cell Therapy.

Human mesenchymal stem/stromal cell (hMSC)-based cell therapies are promising for treating a variety of diseases. The unique immunomodulatory properties of hMSCs have extended their therapeutic potential beyond tissue regeneration. However, extensive pre-clinical culture expansion inevitably drives cells toward replicative "aging" and a consequent decline in quality. These "in vitro-aged" hMSCs resemble biologically aged cells, which have been reported to show senescence signatures, diminished immunosuppressive capacity, and weakened regenerative potential as well as pro-inflammatory features. In this review, we have surveyed the literature to explore the intimate relationship between the inflammatory status of hMSCs and their in vitro aging process. We posit that a shift from an anti-inflammatory to a pro-inflammatory phenotype of culture-expanded hMSCs contributes to a deterioration in their therapeutic efficacy. Potential molecular and cellular mechanisms underpinning this phenomenon have been discussed. We have also highlighted studies that leverage these mechanisms to make culture-expanded hMSCs more amenable for clinical use.

Effective Locations for Injecting Botulinum Toxin into the Mentalis Muscle; Cadaveric and Ultrasonographic Study.

The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed to rejuvenate the lower face. Forty-four adult hemifaces from five Thai cadavers and 21 Korean cadavers were dissected to identify the locations of the mentalis muscle. Sixty-six hemifaces from 33 healthy young Korean subjects were included in an ultrasonographic study. The depth of the mentalis muscle below the skin surface, the thickness of the mentalis muscle, and the distance from the bone to the mentalis muscle were measured at the two points that were 5 mm lateral to the most-prominent point of the chin. The mentalis muscle was classified into two types based to its shape: in type A (86.4%, 38 of the 44 cases) it was dome shaped in three dimensions, while in type B (13.6%, 6 of the 44 cases) it was flat. The mentalis muscle was present mostly at the area 5-10 mm from the midsagittal line and 20-30 mm from a horizontal line connecting the mouth corners. The mentalis muscle was present between depths of 6.7 to 10.7 mm below the skin. This new information about the location of the mentalis muscle may help when identifying the most effective and safe botulinum toxin injection points and depths during esthetic procedures for weakened facial rhytides on the lower face.

Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner.

Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging.

Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.

Neuroprotective Potential of GDF11: Myth or Reality?

In the brain, aging is accompanied by cellular and functional deficiencies that promote vulnerability to neurodegenerative disorders. In blood plasma from young and old animals, various factors such as growth differentiation factor 11 (GDF11), whose levels are elevated in young animals, have been identified. The blood concentrations of these factors appear to be inversely correlated with the age-related decline of neurogenesis. The identification of GDF11 as a "rejuvenating factor" opens up perspectives for the treatment of neurodegenerative diseases. As a pro-neurogenic and pro-angiogenic agent, GDF11 may constitute a basis for novel therapeutic strategies.

In search of a universal and objective method to assess facial aging: The new face objective photo-numerical assessment scale.

Most patients who undergo cosmetic rejuvenation treatment hope to appear younger and healthier. Although a number of scales have been put forward to assess facial aging, to date none has focused on predicting patients' age. The purpose of our study was to validate a more complete version of the face - Objective assessment scale previously developed by the authors. Since patients with a photo-damaged skin can look older than others we created a new sub-scale: the facial photo-aging scale, in order to provide a more comprehensive method for the overall assessment of facial aging. The Rasch model was used as part of the validation process. We assigned a score to each patient based on the scales we have developed. The correlation between a patient's actual age and the obtained scores was analyzed; we also analyzed the inter-rater reliability and test-retest reliability. All the scales exceeded criteria for acceptability, reliability and validity. The facial aging scale we have developed may prove to be a valuable tool to assess patients before and after facial rejuvenation treatment or surgery, as well as for clinical research in the field of facial skin regeneration.

Evaluating the Effects of High RAP Content and Rejuvenating Agents on Fatigue Performance of Fine Aggregate Matrix through DMA Flexural Bending Test.

High percentage reclaimed asphalt pavement (RAP) is prevailing in pavement engineering for its advantages in sustainability and environmental friendliness, however, its fatigue resistance remains a major concern. Fine aggregate matrix (FAM) is a crucial part in the fatigue resistance of asphalt mixtures with high RAP content. Hence, the linear amplitude sweep (LAS) test of FAM has been developed to study the fatigue resistance of asphalt mixtures. However, the torsional loading mode of the LAS test with a dynamic shear rheometer (DSR) is a limitation to simulate traffic load. In this paper, an alternative LAS test for FAM with high RAP content was proposed. Beam FAM specimens were tested using a dual-cantilever flexural loading fixture in a dynamic mechanical analyzer (DMA). To investigate the influence of RAP content and the rejuvenating agent (RA), four kinds of FAM mixes were tested with this method to study their fatigue resistance. The test results suggested that the repeatability of this alternative approach was reliable. A fatigue failure criterion based on maximum C × N was defined. Then, fatigue life prediction models based on viscoelastic continuum damage (VECD) analysis were established according to the LAS test results and validated by a strain-controlled time sweep (TS) test. It turned out that as RAP content increased, the modulus of FAM would be significantly raised, accompanied with a drop in the phase angle. The fatigue life of FAM would be greatly shortened when the RAP binder replacement rate reached 50%. Adding RA could considerably improve the dynamic properties of FAM mixes with high RAP content, resulting in a decrease in modulus, increase in phase angle and elongating fatigue life, but could not recover to the level of virgin binder.

Assessment on Physical and Rheological Properties of Aged SBS Modified Bitumen Containing Rejuvenating Systems of Isocyanate and Epoxy Substances.

Styrene⁻butadiene copolymer (SBS)-modified bitumen (SMB) is widely applied in pavement construction. With yearly services, many SMB wastes urgently need to be reclaimed for repaving roads based on the objectives of environmental protection, landfill saving, as well as resource utilization. The present work is focused on the investigation of the physical and rheological properties of aged SMB incorporated with rejuvenating systems consisting of fluid catalytic cracking slurry (FCC slurry), C12⁻14 aliphatic glycidyl ether (AGE), diphenylmethane diisocyanate (MDI), and other additives. The rejuvenating systems containing the main components of 10% FCC slurry, 10%FCC/3%AGE, and 10%FCC/3%AGE/1% MDI were respectively recorded as Ra, Rb, and Rc. The results indicate that both Rb and Rc have obvious workability that make contributions for improving comprehensive physical properties while slightly reducing the softening point, which were also proven to be effective for the re-rejuvenation of re-aged binder. The higher viscous-elastic temperature caused by the agglomeration of binder molecules in aged SMB could be dropped to a lower value with rejuvenating systems, while improving the low-temperature crack resistance. With the use of the Rb and Rc rejuvenating systems, the high-temperature deformation resistance of aged SMB fell, approaching the performance of fresh SMB. Vibration noise consumption could be improved for aged SMB incorporated with Rb and Rc in the form of viscous loss, while the effects for re-aged SMB containing the same rejuvenating systems were weakened but still effective.

Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease.

BACKGROUND: Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. PATIENTS AND METHODS: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. RESULTS: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11. CONCLUSION: Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11.

Use of platelet-rich fibrin as an autologous biologic rejuvenating media for avulsed teeth - an in vitro study.

AIM: The prognosis of replanted avulsed tooth depends on the existence of viable cells in the periodontal ligament and also on those cells which are able to proliferate on the damaged areas of the root. The purpose of this study was to evaluate the survival of periodontal ligament cells (PDL) when soaked in an autologous biologic rejuvenating media after an extra-oral dry time of 40 min. METHOD: Thirty teeth were selected with intact crown which were advised for Orthodontic extraction having healthy PDL. They were divided into two experimental and two control groups. The positive and negative controls corresponded to 0-min and 1-h dry time, respectively. The experimental teeth were stored dry for 40 min and then immersed in one of the two media, combination of platelet-rich fibrin and platelet poor plasma (PRF+PPP) and PPP for 45 min. The teeth in each group were treated with dispase II and collagenase for 30 min and later centrifuged for 5 min at 50.17 g. The supernatant was removed with sterile micropipette, the cells labelled with 0.4% trypan blue, and the number of viable PDL cells was counted with a haemocytometer, under a light microscope. RESULTS: anova and Mann-Whitney U-test demonstrated statistically significant differences in the viability of PDL cells among experimental groups. CONCLUSION: Within the parameters of this study, a combination of platelet-rich fibrin and PPP demonstrated higher number of viable PDL cells and hence could be a good biologic rejuvenating media for avulsed teeth.