Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

Introduction: Many invasive and noninvasive neurotechnologies are being developed to help treat neurological pathologies and disorders. Making a brain implant safe, stable, and efficient in the long run is one of the requirements to conform with neuroethics and overcome limitations for numerous promising neural treatments. A main limitation is low biocompatibility, characterized by the damage implants create in brain tissue and their low adhesion to it. This damage is partly linked to friction over time due to the mechanical mismatch between the soft brain tissue and the more rigid wires. Methods: Here, we performed a short biocompatibility assessment of bio-inspired intra-cortical implants named \"Neurosnooper\" made of a microelectrode array consisting of a thin, flexible polymer-metal-polymer stack with microwires that mimic axons. Implants were assembled into poly-lactic-glycolic acid (PLGA) biodegradable needles for their intra-cortical implantation. Results and Discussion: The study of glial scars around implants, at 7 days and 2 months post-implantation, revealed a good adhesion between the brain tissue and implant wires and a low glial scar thickness. The lowest corresponds to electrode wires with a section size of 8 μm × 10 μm, compared to implants with the 8 μm × 50 μm electrode wire section size, and a straight shape appears to be better than a zigzag. Therefore, in addition to flexibility, size and shape parameters are important when designing electrode wires for the next generation of clinical intra-cortical implants.

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.

Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of -1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p = 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p = 0.166; average supination: 83.5° vs. 85.7°, p = 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p = 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusions: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries.

Currently, titanium and its alloys have emerged as the predominant metallic biomaterials for orthopedic implants. Nonetheless, the relatively high post-operative infection rate (2-5%) exacerbates patient discomfort and imposes significant economic costs on society. Hence, urgent measures are needed to enhance the antibacterial properties of titanium and titanium alloy implants. The titanium dioxide nanotube array (TNTA) is gaining increasing attention due to its topographical and photocatalytic antibacterial properties. Moreover, the pores within TNTA serve as excellent carriers for chemical ion doping and drug loading. The fabrication of TNTA on the surface of titanium and its alloys can be achieved through various methods. Studies have demonstrated that the electrochemical anodization method offers numerous significant advantages, such as simplicity, cost-effectiveness, and controllability. This review presents the development process of the electrochemical anodization method and its applications in synthesizing TNTA. Additionally, this article systematically discusses topographical, chemical, drug delivery, and combined antibacterial strategies. It is widely acknowledged that implants should possess a range of favorable biological characteristics. Clearly, addressing multiple needs with a single antibacterial strategy is challenging. Hence, this review proposes systematic research into combined antibacterial strategies to further mitigate post-operative infection risks and enhance implant success rates in the future.

UNASSIGNED: Socket preservation is a surgical procedure aimed at preserving the dimensions of the alveolar bone following tooth extraction. It is performed by filling the extraction socket with bone graft material with or without a barrier membrane. Recently, dentine obtained from extracted teeth has been tried as an autograft for socket preservation. Studies have compared the use of dentin to other bone grafts, however, systematic reviews evaluating the efficacy of dentin for socket preservation are limited. Hence, this systematic review protocol is proposed to generate evidence on the efficacy of dentin as a viable alternative to other bone graft materials for socket preservation.
UNASSIGNED: This systematic review protocol was prepared according to the Methodological Expectations of the Cochrane Intervention Reviews (MECIR) guidelines. It will be conducted using the Cochrane Handbook for Systematic Review of Interventions. PubMed, Scopus, Web of Science, EMBASE, Epistemonikos, Cochrane Central, and EBSCO databases and clinical trial registries, will be searched for all randomized controlled trials (RCTs) and non-randomized studies that have used autologous dentin graft (either in particulate/putty, or/matrix form) for socket preservation. The radiographic and clinical assessment of bone and soft tissue healing of the preserved sockets along with patient-related outcomes following surgery will be assessed. The risk of bias assessment of the RCTs and Non-RCTs will be assessed using the \'Cochrane Risk of Bias assessment tool (ROB II) and ROBINS-I respectively. The certainty of evidence will be assessed by the GRADE approach.
UNASSIGNED: This evidence is important for dental clinicians and the public to make an informed decision when choosing graft material for socket preservation. The extracted teeth are considered biological waste; however, this evidence provides scope for using a less invasive autograft for bone regenerative procedures.
UNASSIGNED: PROSPERO: CRD42021201958 (Registered on 15/02/2021).

BACKGROUND: This clinical study investigates platelet-rich fibrin\'s (PRF) impact on dental implant stability, addressing global oral health challenges and limitations of traditional methods. Emphasizing osseointegration\'s pivotal role, the study explores PRF\'s potential in enhancing implant stability, assessing it through resonance frequency analysis (RFA) and implant stability quotient (ISQ). The hypothesis suggests PRF may improve both primary and secondary stability, aiming to uncover clinical benefits in dental implant procedures Materials and methods: The study involved 24 subjects from the Department of Periodontics outpatient clinics with a meticulously designed methodology. This included a pre-surgical protocol with oral prophylaxis, impressions, and cone-beam computed tomography (CBCT) analysis. PRF preparation utilized a minimally invasive venipuncture technique. Implant placement followed a two-stage surgical protocol, assessing primary stability with MEGA ISQ (Ostell). Post-surgery, patients received instructions and underwent recall for secondary stability after three months. Clinical parameters such as plaque index (PI), gingival index (GI), implant probing pocket depth (IPPD), sulcus bleeding index (SBI), and implant stability (IS) were systematically recorded. Robust statistical analyses, using IBM SPSS Statistics for Windows v20.0 (IBM Corp., Armonk, USA) software, incorporated Mann-Whitney U and Wilcoxon signed-rank tests for group and within-time point comparisons, with a significance level of p<0.05. This comprehensive study yields nuanced insights into the impact of PRF and implant procedures on key clinical parameters, contributing significantly to the field.
RESULTS: This study compared dental implants with and without PRF in 24 patients. Both groups showed significant improvements in the PI, GI, and SBI. The PRF group exhibited higher IS in the third and sixth months, while IPPD was lower in the PRF group in the sixth month.
CONCLUSIONS: The findings of the study highlight a positive impact on implant stability contributing to better implant outcomes.

Implant-associated infections present a significant clinical obstacle for orthopedic practitioners, with bacterial biofilm formation serving as a pivotal factor in the initiation, progression, and management of such infections. Conventional approaches have proven inadequate in fully eradicating biofilm-related infections. Consequently, novel material-based therapeutic strategies have been developed, encompassing the utilization of antimicrobial agents, delivery vehicles, and synergistic antibacterial systems. In this review, we provide a succinct overview of recent advancements in anti-biofilm strategies, with the aim of offering insights that may aid in the treatment of intraosseous implant infections.

BACKGROUND: This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides.
METHODS: 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area.
RESULTS: BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group.
CONCLUSIONS: Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.