The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient-friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available. However, these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remain high. This paper describes three infected tibial defect nonunions with a segmental defect over 10 centimeters long treated with a three-dimensional (3D)-printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the ages of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than 10 centimeters (range 11-15cm). First-stage MPs consisted of extensive debridement, external fixation, and placement of anterior lateral thigh flaps. Positive cultures were obtained from all patients during this first stage, which were treated with specific systemic antibiotics for 12 weeks. The second-stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure, a custom 3D-printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA-derived autograft, iFactor, and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT scans six months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight bearing. This case report shows that 3D-printed PCL-TCP cages in combination with biological adjuncts are a novel addition to the surgical treatment of very large bone defects in (infected) post-traumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication.

This review aimed to answer the general question of whether autologous platelet concentrates (APCs, an autologous blood-derivative) can improve the outcome of alveolar bone augmentation. Three clinical scenarios were assessed: horizontal/vertical bone augmentation in combination with implant placement (simultaneous approach), horizontal bone augmentation in a staged approach, and vertical bone augmentation in a staged approach. An electronic literature search strategy was conducted for each review from the outset to July 1st, 2023. The titles and abstracts (when available) of all identified studies were screened and imported into a database. If articles appeared to meet the inclusion criteria or their title and abstract had insufficient data, the full text was obtained to make the final decision. All studies that met the inclusion criteria underwent data extraction. Moreover, the references of the identified papers were screened for additional studies. After title and abstract screening and selection criteria application, 14 clinical studies were included for the qualitative analysis: seven for horizontal/vertical bone augmentation in a simultaneous approach, five for horizontal bone augmentation in a staged approach, and two for vertical bone augmentation in a staged approach. There is scarce literature regarding the added value of APCs in bone augmentation, and most studies had small sample sizes, a lack of standardized protocols, and different outcome variables, which makes comparisons between studies difficult. Out of the 14 studies, four were well-designed randomized clinical trials, where we could find better results for the APCs groups. Most studies, particularly comparative and well-designed studies, demonstrated beneficial and promising results of using APCs in alveolar bone augmentation. However, before high-level evidence-based conclusions can be drawn, more randomized clinical trials must compare the benefits of adding APCs to the gold-standard approach.

OBJECTIVE: The aim of this systematic review and meta-analysis was to assess possible histomorphometric differences in new bone formation and in remaining graft particles when hyaluronic acid (HA) was added and mixed with graft materials in bone regeneration.
METHODS: This review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) of the National Institute of Health Research (registration number CRD42024530030). Electronic research was performed, and involved studies published up to 29 February 2024 using a specific word combination. The primary outcome was to assess possible histomorphometric differences in new bone formation and in remaining graft particles when HA was added and mixed with graft materials in bone regeneration. The search resulted in 138 potential studies. Meta-analyses were performed using the fixed and random effects model to identify significant changes in new bone formation and in the remaining graft particles.
RESULTS: After screening procedures, only three randomized controlled trials fulfilled the inclusion criteria and were selected for qualitative and quantitative analysis. The effect size of HA in the new bone formation was not statistically significant at 95% CI (Z = 1.734, p-value = 0.083, 95 % CI -,399; 6516). The effect size of HA in the remaining graft particles was not statistically significant at 95% CI (Z = -1.042, p-value = 0.297, CI -,835; 255).
CONCLUSIONS: Within the limitations of the present systematic review and meta-analysis, the addition of HA to bone graft did not result in significant changes in bone regeneration procedures in terms of new bone formation and residues, even if the included studies showed encouraging and promising results.

BACKGROUND: Marine ecosystems, covering 70% of Earth\'s surface, hold immense biodiversity and potential for biomaterials. Cuttlefish bone (CB) and marine resources have gained attention as eco-friendly biomaterials.
OBJECTIVE: We aim to comprehensively study biomedical applications of CB-derived materials. By evaluating both in vivo and in vitro investigations, the review seeks to uncover the diverse potential of CB in the biomedical field.
METHODS: A comprehensive search of electronic databases yielded 51 articles from 2408 studies. These studies encompassed in vivo animal studies and in vitro investigations.
RESULTS: In vivo studies employed for bone repair, dorsal subcutaneous defects, thermal wound healing, muscle injections, and avian blood testing. In vitro studies focused on HAp synthesis, scaffold development, dental material enhancement, and antimicrobial properties. Risk of bias assessments revealed varying degrees of methodological quality in both animal and in vitro studies, underscoring the need for standardised reporting and rigorous study design in future research.
CONCLUSIONS: This review fills a gap in the literature by providing a comprehensive overview of the applications of CB-derived materials in the biomedical field. Additionally, it offers valuable insights for researchers, clinicians, and policymakers interested in sustainable and effective biomaterials for diverse medical purposes, advancing the fields of regenerative medicine and dentistry.

Autogenous dentin matrix (ADM), derived from a patient\'s extracted tooth, can be repurposed as an autologous grafting material in reconstructive dentistry. Extracted teeth provide a source for ADM, which distinguishes itself with its low rejection rate, osteoinductive capabilities and ease of preparation. Consequently, it presents a viable alternative to autogenous bone. Animal studies have substantiated its effective osteoinductive properties, while its clinical applications encompass post-extraction site preservation, maxillary sinus floor augmentation, and guided bone tissue regeneration. Nevertheless, the long-term efficacy of ADM applied in bone regeneration remains underexplored and there is a lack of standardization in the preparation processes. This paper comprehensively explores the composition, mechanisms underlying osteoinductivity, preparation methods, and clinical applications of ADM with the aim of establishing a fundamental reference for future studies on this subject.

Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.

Fracture healing is a dynamic process essential for the restoration of bone integrity and function. However, factors such as patient age, comorbidities, and the severity of the fracture can impede this process, leading to delayed healing or nonunion. Platelet-rich plasma (PRP) has emerged as a promising therapeutic option for enhancing fracture healing. PRP is an autologous blood product containing a concentrated mixture of platelets, growth factors, and cytokines known to promote tissue regeneration and repair. This comprehensive review provides an overview of the fracture healing process, emphasizing the importance of timely and efficient bone repair. We discuss the mechanisms underlying the purported efficacy of PRP in fracture healing, drawing upon both preclinical and clinical evidence. Preclinical studies in animal models have demonstrated the ability of PRP to accelerate fracture healing, stimulate osteogenesis, and enhance bone regeneration. Clinical studies have yielded mixed results, with some reporting positive outcomes in terms of accelerated healing and improved functional outcomes, while others have shown no significant benefits over standard treatments. Factors influencing the efficacy of PRP, such as timing of administration, PRP concentration, and patient-specific variables, are also examined. Furthermore, safety considerations and potential adverse effects associated with PRP therapy are discussed. Despite the promising preclinical findings, challenges remain in standardizing PRP formulations, optimizing administration protocols, and addressing unanswered questions regarding its long-term efficacy and safety. This review aims to provide insights into the therapeutic potential of PRP in fracture healing, informing future research directions and guiding clinical practice.

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 search to optimize the healing and bone repair processes in oral and maxillofacial surgeries reflects the constant evolution in clinical practice, driven by the demand for increasingly satisfactory results and the need to minimize postoperative complications.
OBJECTIVE: To evaluate the efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing and bone repair process in oral and maxillofacial surgeries.
METHODS: The systematic review protocol for this study included the definition of the research question, the domain of the study, the databases searched, the search strategy, the inclusion and exclusion criteria, the types of studies to be included, the measures of effect, the methods for screening, data extraction and analysis, and the approach to data synthesis. Systematic literature searches were carried out on Cochrane databases, Web of Science, PubMed, ScienceDirect, Embase and Google Scholar.
RESULTS: The strategic search in the databases identified 1,159 studies. After removing the duplicates with the Rayyan© software, 946 articles remained. Of these, 30 met the inclusion criteria. After careful evaluation based on the inclusion and exclusion criteria, 8 studies were considered highly relevant and included in the systematic review.
CONCLUSIONS: Platelet and Leukocyte Rich Fibrin (L-PRF) has a positive effect on the healing process and bone repair in oral and maxillofacial surgeries.