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Anterior cruciate ligament (ACR) rupture is a frequent injury in professional sports players. We conducted a retrospective cohort study, including 41 professional female handball players, undergoing ACR reconstruction surgery, using a Ligament Advanced Reinforcement System (LARS) graft (n = 12) or a Soft Tissue (ST) graft (n = 29). After return-to-play, the patients were asked to take a survey, reporting subjective and objective performance indexes before the injury and after return-to-play. Time from surgery to first practice and to return-to-play were significantly shorter in the LARS group (3.92 ± 1.14 vs. 6.93 ± 2.19 months, p < 0.001 and 4.71 ± 1.2 vs. 8.81 ± 2.9, respectively). While there was no difference between postoperative mean time on court, number of goals/match, number of matches played at 6 months return-to-play and 50 m, 100 m and gate-to-gate sprint times, there was a significantly greater increase in preoperative times in the ST group than in the LARS group (1.45 ± 1.05 s vs. 0.21 ± 0.58 s slower than preoperatively, p < 0.001 for 50 m; 1.09 ± 0.95 s vs. 0.08 ± 1 s, p = 0.01 for 100 m; 1.66 ± 1 s vs. 0.21 ± 0.66 s for gate-to-gate). In conclusion, LARS grafts provide a faster recovery time and better functional outcome, significantly impacting the performance of professional handball players.

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Lesions of the articular cartilage are frequent in all age populations and lead to functional impairment. Multiple surgical techniques have failed to provide an effective method for cartilage repair. The aim of our research was to evaluate the effect of two different compression forces on three types of cartilage repair using finite element analysis (FEA). Initially, an in vivo study was performed on sheep. The in vivo study was prepared as following: Case 0-control group, without cartilage lesion; Case 1-cartilage lesion treated with macro-porous collagen implants; Case 2-cartilage lesion treated with collagen implants impregnated with bone marrow concentrate (BMC); Case 3-cartilage lesion treated with collagen implants impregnated with adipose-derived stem cells (ASC). Using the computed tomography (CT) data, virtual femur-cartilage-tibia joints were created for each Case. The study showed better results in bone changes when using porous collagen implants impregnated with BMC or ASC stem cells for the treatment of osseocartilaginous defects compared with untreated macro-porous implant. After 7 months postoperative, the presence of un-resorbed collagen influences the von Mises stress distribution, total deformation, and displacement on the Z axis. The BMC treatment was superior to ASC cells in bone tissue morphology, resembling the biomechanics of the control group in all FEA simulations.

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Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 µm and 86.9 µm) at the peri-implant area, compared to control (43.2 µm and 39.2 µm), enoxaparin (39.6 µm and 24 µm), and fondaparinux (36.2 µm and 32.7 µm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.

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Background and aim: Despite the great success of primary total hip arthroplasty (THA), the number of revisions has significantly increased over the past years. The objectives of the study were to investigate the main causes that lead to revision of THA, the time interval between primary THA and revision, and the results of the revision surgery. We also assessed whether there was any correlation between the patients' age, BMI, diagnosis for primary THA and the cause of failure. Methods: This paper retrospectively analyzed 189 patients with THA revision surgery performed over a six-year period, between 2015 and 2020. Patients' charts were reviewed to collect data on patient's demographics, patient's primary THA and revision procedures, and the time interval between primary THA and revision surgery. Patients were divided into 3 groups according to the time interval THA-revision: group I (<5 years), group II (5-10 years) and group III (>10 years). Results: The patients' mean age (82 men/107 women) was 69.59±7.85 years (range 31-92 years). The most frequent revision cause was aseptic loosening (52%), followed by periprosthetic fractures (18%), infection (17%) and persistent hip instability (12%). Patients' age (r=0.43) and BMI (r=-0.4) had low correlation with the time interval between THA and revision. Conclusions: The main causes for revision THA within less than five years are infection and instability, while revision for aseptic loosening is performed especially after five years from the primary THA. Osteonecrosis, post-traumatic osteoarthritis and femoral neck fracture are correlated with a higher incidence of revision at less than five years from the primary THA.

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Innovative nanomaterials are required for the coatings of titanium (Ti) implants to ensure the activation of Ti surfaces for improved osseointegration, enhanced bone fracture healing and bone regeneration. This paper presents a systematic investigation of biomimetic composite (BC) coatings on Ti implant surfaces in a rat model of a diaphyseal femoral fracture. Methodological approaches of surface modification of the Ti implants via the usual joining methods (e.g., grit blasting and acid etching) and advanced physicochemical coating via a self-assembled dip-coating method were used. The biomimetic procedure used multi-substituted hydroxyapatite (ms-HAP) HAP-1.5 wt% Mg-0.2 wt% Zn-0.2 wt% Si nanoparticles (NPs), which were functionalized using collagen type 1 molecules (COL), resulting in ms-HAP/COL (core/shell) NPs that were embedded into a polylactic acid (PLA) matrix and finally covered with COL layers, obtaining the ms-HAP/COL@PLA/COL composite. To assess the osseointegration issue, first, the thickness, surface morphology and roughness of the BC coating on the Ti implants were determined using AFM and SEM. The BC-coated Ti implants and uncoated Ti implants were then used in Wistar albino rats with a diaphyseal femoral fracture, both in the absence and the presence of high-frequency pulsed electromagnetic shortwave (HF-PESW) stimulation. This study was performed using a bone marker serum concentration and histological and computer tomography (micro-CT) analysis at 2 and 8 weeks after surgical implantation. The implant osseointegration was evaluated through the bone-implant contact (BIC). The bone-implant interface was investigated using FE-SEM images and EDX spectra of the retrieved surgical implants at 8 weeks in the four animal groups. The obtained results showed significantly higher bone-implants contact and bone volume per tissue volume, as well as a greater amount of newly formed bone, in the BC-coated Ti implants than in the uncoated Ti implants. Direct bone-implant contact was also confirmed via histological examination. The results of this study confirmed that these biomimetic composite coatings on Ti implants were essential for a significant enhancement of osseointegration of BC-coated Ti implants and bone regeneration. This research provides a novel strategy for the treatment of bone fractures with possible orthopedic applications.

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INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia-ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia-ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. OBJECTIVES: The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. METHODS: The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7th postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O2 for 90 minutes) and some groups to hypothermia. RESULTS: In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon's Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. CONCLUSION: The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment.

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PURPOSE: The purpose of this article is to describe the novel technique of arthroscopic-assisted reduction and internal fixation (ARIF) of talar neck fractures, presenting also the outcomes of this treatment method in a series of four patients. METHODS: Between 2011 and 2019, we have treated in our service a number of four patients with talar neck fractures, by the arthroscopic technique. The surgical intervention consists in arthroscopic exploration of tibiotalar and subtalar joints, arthroscopic lavage and debridement, reduction, and osteosynthesis with two cannulated screws under both arthroscopic and fluoroscopic control. Post-operative care consists in non-weightbearing immobilization for 6 weeks, followed by partial loading under the protection of a walking brace for the next six weeks and ROM exercises. The patients were followed up at three  months, when a CT scan was performed, and at one year, when X-ray images showed the consolidation of fractures. RESULTS: Normal or slightly reduced ROM of the ankle and hindfoot was noted in three out of four patients, absence of any pain, or disability (3 patients). The AOFAS' Ankle-Hindfoot scale showed good and excellent results; mean score was 92.75 points (86-98p) at one year after the surgery. CONCLUSION: Arthroscopic-assisted management of talar fractures offers the advantages of minimally invasive surgery combined with good visualization of the fracture, good control of anatomic reduction, and the possibility to treat associated lesions. Main disadvantages of the method are technical difficulties, requires a prolonged learning curve, and offers limited fixation alternatives.

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OBJECTIVES: The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement. MATERIALS AND METHODS: Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers. RESULTS: Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant. CONCLUSION: The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

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Thyroid hormones are important factors that regulate metabolism and cell differentiation throughout the human body. A complication of thyroid pathology is represented by an alteration of the bone metabolism which can lead to osteoporosis and fragility fractures, known to have a high mortality rate. Although there is a consensus on the negative impact of hyperthyroidism on bone metabolism, when referring to hypothyroidism, subclinical hypothyroidism, or subclinical hyperthyroidism, there is no general agreement. The aim of our review was to update clinicians and researchers about the current data regarding the bone health in hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism patients. Thyroid disorders have an important impact on bone metabolism and fracture risk, such that hyperthyroidism, hypothyroidism, and subclinical hyperthyroidism are associated with a decreased bone mineral density (BMD) and increased risk of fracture. Subclinical hypothyroidism, on the other hand, is not associated with osteoporosis or fragility fractures, and subclinical hyperthyroidism treatment with radioiodine could improve bone health.

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Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered pharmacological agents have been proved to improve the anabolic response in the case of cartilage lesions. Alendronate, glucosamine, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, vitamin C, vitamin D, aspirin and strontium ranelate have shown positive results in clinical trials. On the other hand, calcitonin, risedronate, doxycycline, and celecoxib did not slow the progression of cartilage lesions in clinical trials. Other systemic drugs or supplements such as teriparatide, leptin, zoledronic acid, bevacizumab, atorvastatin, omega-3 fatty acid, naringin, MSM, selenium, zinc, magnesium, resveratrol, donepezil, naproxen, etodolac, ursodeoxycholic acid (UDCA), lithium chloride, and rebamipide showed positive results in in vitro and animal studies but clinical trials are needed to confirm the positive impact on cartilage repair. A number of molecules, not currently available on the market, have also shown promising results in cartilage healing, such as licofelone, sclerostin, cyclopamine, cyclodextrin polysulfate, AG-041R, osteoprotegerin, rhMK, ß-cryptoxanthine, NF-κb essential modulator binding domain (NBD), TGF-ß-neutralizing antibody, osteogenic protein-1 (BMP-7), fibroblast growth factor 2 (FGF2), and RhBMP-2. Currently available systemic drugs that impair cartilage healing are represented by corticosteroids, vitamin A, and fluoroquinolones.

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PURPOSE: Bone consolidation after severe trauma is the most challenging task in orthopedic surgery. This study aimed to develop biomimetic composite for coating Ti implants. Afterwards, these implants were tested in vivo to assess bone consolidation in the absence or the presence of high-frequency pulsed electromagnetic short-waves (HF-PESW). MATERIALS: Biomimetic coating was successfully developed using multi-substituted hydroxyapatite (ms-HAP) functionalized with collagen (ms-HAP/COL), embedded into poly-lactic acid (PLA) matrix (ms-HAP/COL@PLA), and subsequently covered with self-assembled COL layer (ms-HAP/COL@PLA/COL, named HAPc). METHODS: For in vivo evaluation, 32 Wistar albino rats were used in four groups: control group (CG) with Ti implant; PESW group with Ti implant+HF-PESW; HAPc group with Ti implant coated with HAPc; HAPc+PESW group with Ti implant coated with HAPc+HF-PESW. Left femoral diaphysis was fractured and fixed intramedullary. From the first post-operative day, PESW and HAPc+PESW groups underwent HF-PESW stimulation for 14 consecutive days. Biomimetic coating was characterized by XRD, HR-TEM, SEM, EDX and AFM. RESULTS: Osteogenic markers (ALP and osteocalcin) and micro-computed tomography (CT) analysis (especially bone volume/tissue volume ratio results) indicated at 2 weeks the following group order: HAPc+PESW>HAPc≈PESW (P>0.05) and HAPc+PESW>control (P<0.05), indicating the higher values in HAPc+PESW group compared to CG. The fracture-site bone strength showed, at 2 weeks, the highest average value in HAPc+PESW group. Moreover, histological analysis revealed the most abundant COL fibers assembled in dense bundles in HAPc-PESW group. At 8 weeks, micro-CT indicated higher values only in HAPc+PESW group vs CG (P<0.05), and histological results showed a complete-healed fracture in groups: HAPc+PESW, HAPc and PESW, but with more advanced bone remodeling in HAPc+PESW group. CONCLUSION: Using Ti implants coated by HAPc jointly with HF-PESW stimulation positively influenced the bone consolidation process, especially in its early phase, thus potentially providing a superior strategy for clinical applications.

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In vitro studies showed that high-frequency pulsed electromagnetic fields (HF-PEMFs) increase the activity/expression of early and late osteogenic markers and enhance bone mineralization. The main aim of this study was to investigate the in vivo effects of HF-PEMFs on fracture healing using a rat model. A femur fracture was established by surgery in 20 male Wistar rats. Titanium nails were implanted to reduce and stabilize the fracture. After surgery, 20 rats were equally divided into untreated control and treated group (from the first postoperative day HF-PEMFs at 400 pulses/sec [pps] were applied for 10 minutes/day, for two weeks). Quantitative and qualitative assessment of bone formation was made at two and eight weeks following surgery and included morphological and histological analysis, serological analysis by ELISA, micro-computed tomography (micro-CT), and three-point bending test. At two weeks in HF-PEMF group, soft callus was at a more advanced fibrocartilaginous stage and the bone volume/total tissue volume (BV/TV) ratio in the callus area was significantly higher compared to control group (p = 0.047). Serum concentration of alkaline phosphatase (ALP) and osteocalcin (OC) was significantly higher in HF-PEMF group (ALP p = 0.026, OC p = 0.006) as well as the mechanical strength of femurs (p = 0.03). At eight weeks, femurs from HF-PEMF group had a completely formed woven bone with dense trabeculae, active bone marrow, and had a significantly higher BV/TV ratio compared to control (p = 0.01). HF-PEMFs applied from the first postoperative day, 10 minutes/day for two weeks, enhance bone consolidation in rats, especially in the early phase of fracture healing.

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Bone is a complex tissue with unique properties such as high strength and regeneration capabilities while carrying out multiple functions. Bone regeneration occurs both in physiological situations (bone turnover) and in pathological situations (e.g. fractures), being performed by osteoblasts and osteoclasts. If this process is inadequate, fracture nonunion or aseptic loosening of implants occurs and requires a complex treatment. Exogenous factors are currently used to increase bone regeneration process when needed, such as bisphosphonates and vitamin D, but limitations do exist. Cannabinoid system has been shown to have positive effects on bone metabolism. Cannabinoids at bone level mainly act on two receptors called CB-1 and CB-2, but GPR55, GPR119, TPRV1, TPRV4 receptors may also be involved. The CB-2 receptors are found in bone cells at higher levels compared to other receptors. Endocannabinods represented by anandamide and 2-arachidonoylglycerol, can stimulate osteoblast formation, bone formation and osteoclast activity. CB-2 agonists including HU-308, HU-433, JWH133, and JWH015 can stimulate osteoblast proliferation and activity, while CB-2 antagonists such as AM630 and SR144528 can inhibit osteoclast differentiation and function. CB-1 antagonist AM251 has been shown to inhibit osteoclast differentiation and activity, while GPR55 antagonist cannabidiol increases osteoblast activity and decreases osteoclast function. An optimal correlation of dose, duration, moment of action, and affinity can lead to an increased bone regeneration capacity, with important benefits in many pathological situations which involve bone tissue. As adverse reactions of cannabinoids have not been described in patients under controlled medication, cannabinoids can represent future treatment for bone regeneration.

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BACKGROUND: The aim was to assess the effects of periodontal disease in promoting liver fibrosis in a rat model of ligature-induced periodontitis. METHODS: Twenty-four Wistar rats were divided into four groups: control (CTRL), experimental periodontitis group at day 7 (PER7), at day 14 (PER14), at day 21 (PER21). Experimental periodontitis was induced by the placement of a silk ligature around mandibular incisors. The following parameters were assessed: gingival index, tooth mobility; liver status, and portal vein caliber by ultrasound examination; bone retraction, bone mineral density (BMD), bone volume/tissue volume (BV/TV) by micro-CT analysis; aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT); oxidative stress (malondialdehyde [MDA], reduced glutathione/oxidative glutathione ratio [GSH/GSSG]), and matrix metalloproteinase-8 (MMP-8) levels; and histopathological evaluation of periodontal and liver tissues. RESULTS: Periodontal parameters showed the development of periodontitis in experimental groups. Micro-CT results indicates an increase of bone retraction and BMD values and a decrease of BV/TV value in PER groups. Liver fibrosis could not be diagnosed with ultrasound examination in any of the groups. Elevated levels of ASAT and ALAT in PER groups compared with CTRL group were found. MDA have indicated elevated levels and a decrease of GSH/GSSG ratio in PER group compared with the CTRL group. Levels of MMP-8 have indicated high values in PER21 compared with the other groups. Histological analysis of the periodontal and liver tissues sustains the link between periodontal and hepatic injury. CONCLUSION: This study demonstrates a positive correlation between periodontal lesions and liver disease. Periodontitis may be an independent risk factor for liver fibrosis.

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