The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

OBJECTIVE: This study aimed to evaluate the intensity of the subacute local biological effects after implantation and osseoconductive potential of novel hydroxyapatite-based bone substitute coated with poly (lactide-co-glycolide), named ALBO-OS, in comparison to Bio-Oss®.
METHODS: Fifteen male Wistar rats, randomly assigned into groups: 10, 20, and 30 days (n꞊5), were subcutaneously implanted with ALBO-OS and Bio-Oss®. Furthermore, artificially made bone defects on both rat\'s tibias were implanted with experimental materials. Unimplanted defects represented negative control. After the animals\' euthanizing, tissue samples were prepared and analyzed histologically and histomorphometrically.
RESULTS: Normal healing of the epithelial tissue was observed, with no signs of infection or necrosis. Minimal vascular congestion was noted immediately around the graft, with no signs of tissue oedema, with a minimal capsule thickness. The applied material did not cause an inflammatory response (IR) of significant intensity, and 20 days after implantation, the IR was mainly assessed as minimal. The tibial specimen showed that ALBO-OS has good osseoconductive potential, similar to Bio-Oss®, as well as low levels of acute and subacute inflammation.
CONCLUSIONS: The tested material exhibits satisfying biocompatibility, similar to Bio-Oss®.

Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).

This study investigated the impact of adding hydroxyapatite nanoparticles to implant surfaces treated with zirconia blasting and acid etching (ZiHa), focusing on structural changes and bone healing parameters in low-density bone sites. The topographical characterization of titanium discs with a ZiHa surface and a commercially modified zirconia-blasted and acid-etched surface (Zi) was performed using scanning electron microscopy, profilometry, and surface-free energy. For the in vivo assessment, 22 female rats were ovariectomized and kept for 90 days, after which one implant from each group was randomly placed in each tibial metaphysis of the animals. Histological and immunohistochemical analyses were performed at 14 and 28 days postoperatively (decalcified lab processing), reverse torque testing was performed at 28 days, and histometry from calcified lab processing was performed at 60 days The group ZiHa promoted changes in surface morphology, forming evenly distributed pores. For bone healing, ZiHa showed a greater reverse torque, newly formed bone area, and bone/implant contact values compared to group Zi (p < 0.05; t-test). Qualitative histological and immunohistochemical analyses showed higher features of bone maturation for ZiHa on days 14 and 28. This preclinical study demonstrated that adding hydroxyapatite to zirconia-blasted and acid-etched surfaces enhanced peri-implant bone healing in ovariectomized rats. These findings support the potential for improving osseointegration of dental implants, especially in patients with compromised bone metabolism.

Background: Tooth infraocclusion is a process in which a completely or partially erupted tooth gradually moves away from the occlusal plane. Submerged teeth can lead to serious complications. Treating teeth with infraocclusion is very challenging. One of the procedures allowing for the replacement of a missing tooth is autotransplantation. The aim of this paper is to review the literature on teeth autotransplantation, supported by a case report involving the autotransplantation of a third mandibular molar into the site of an extracted infraoccluded first mandibular molar, as well as the utilization of advanced platelet-rich fibrin (A-PRF) alongside autogenous dentin grafts for bone tissue regeneration. Methods: A severely infraoccluded first permanent right mandibular molar was extracted and then ground to obtain the dentin graft. A-PRF clots (collected from the patient\'s peripheral blood) were added to the autogenous dentin graft, to create the A-PRF membrane. An atraumatic extraction of the lower left third molar was performed and then it was transplanted into the socket of tooth no. 46. Immediately after transplantation, tooth no. 38 was stabilized with orthodontic bracket splints for 3 months. The patient attended regular follow-up visits within 12 months. Results: After one year, the patient did not report any pain. In the clinical examination, the tooth and surrounding tissues did not show any signs of infection. However, radiographically, cervical inflammatory resorption, unchanged pulp canal dimensions, absent root growth, periapical radiolucency, and lack of apical and marginal healing were observed. Reconstruction of the bone defect was obtained and the alveolar ridge of the mandible was preserved. Due to poor stability of the tooth and severe resorption, the tooth needed to be extracted. Conclusions: This study is designed to critically evaluate the efficacy of autotransplantation, the application of growth factors, and the integration of autogenous dentin grafts in remedying dental deficiencies resulting from reinclusion. We aim to point out the possible causes of treatment failure.

Background: Maxillary sinus lift is a well-documented and accepted technique in the rehabilitation of the posterior maxilla. Schneiderian membrane perforation is the most common complication and may occur in between 7% and 56% of cases. Different materials and techniques have been described to achieve reparation of the perforation. The aim of this study was to establish whether the perforation of the Schneiderian membrane and its repair during maxillary sinus lift surgery results in a lower implant survival rate compared to those cases where the membrane has not been perforated. Materials and methods: A systematic review and meta-analysis of studies assessing the survival rate of implants placed in regenerated sinus using the lateral window approach, where the perforation of the Schneiderian membrane occur, was carried out. Statistical analysis was performed with Open Meta-Analyst, calculating the odds ratio of implants placed in perforated sinuses and non-perforated sinuses. Results: Ten articles were included in the qualitative analysis and seven articles in the quantitative analysis or meta-analysis. A total of 1224 maxillary sinus augmentation surgeries were performed without perforation of the Schneiderian membrane and 2725 implants were placed; 62 implants failed during the follow-up period with an overall survival rate of 97.7%. In 480 perforated sinuses, 1044 implants were placed, of which 30 failed; the overall survival rate was 97.1%. There were no significant differences between the implant survival rate of the implants in the two groups (OR = 0.78; CI = 0.49-2.23; p = 0.28 and I2 heterogeneity: 0%, p = 0.44). Conclusions: Schneiderian membrane perforation, as long as it is repaired, does not appear to negatively influence implant survival rate. Membrane perforation should not be considered a reason to abort the procedure or an absolute contraindication to implant placement.

Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft-hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double-network hydrogel and 3D-printed PCL was thus prepared and features highly extracellular matrix-mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near-infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on-demand release of Zn2+, which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro-regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft-hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on-demand ion delivery) cues for accelerated healing of diabetic bone defects.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

Bertolotti\'s syndrome is a syndrome in which the transverse process of the most caudal lumbar vertebra becomes enlarged and articulates with the sacral alar, causing back pain. Here, we report a case of an adolescent basketball player with Bertolotti\'s syndrome who was unable to resume playing despite conservative treatment and underwent an endoscopic partial transverse process and sacral alar resection. A 16-year-old male basketball player presented to our hospital with a chief complaint of left low back pain during exercise and prolonged sitting for over one month. No obvious neurological abnormality was found. X-rays and CT showed lumbosacral transitional vertebrae, and the left transverse process of the sixth lumbar vertebra articulated with the sacrum and iliac, which was the Castellvi classification IIA. A block injection into the articulated surface produced improvement in pain, but the effect was not sustained. Since the patient was refractory to conservative treatments, such as medication and physiotherapy, surgery was performed. During surgery, the articulated transverse process and sacral alar were partially resected endoscopically. Because of the proximity of the resection site to the S1 nerve root, intraoperative electromyography (free-run EMG) was used to detect nerve root irritation symptoms in real time. The patient had no postoperative complications, his low back pain improved immediately, and he returned to play basketball three months after surgery. One year after surgery, the bone resection site showed gradual bone regeneration, and two years after surgery, the transverse process and sacral alar showed a bony bridge. The transverse process was enlarged compared to immediately after surgery but remained smaller than that before surgery. The patient continued to play basketball for two years after surgery without back pain, and no symptoms due to bone regeneration appeared. In the present case, a partial resection of the transverse process and sacral alar was performed with good results. Because the bone resection site was close to the S1 nerve root, the use of an endoscope and intraoperative free-run EMG allowed for a safer procedure during the bone resection. In addition, the patient did not present with symptoms that would affect his basketball performance, although the bone regenerated and bridging occurred between the transverse process and sacral alar over a two-year postoperative course.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.