Spinal fusion is a prevalent surgical intervention for degenerative spinal diseases, with increasing demand driven by ageing populations. The coexistence of multiple chronic conditions, termed multimorbidity, often complicates surgical outcomes, making advanced bone grafts crucial for successful fusions. This paper reviews the development, clinical application, and controversies surrounding the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal fusion surgeries. A comprehensive narrative review was conducted, focusing on literature from January 1980 to January 2024, sourced from PubMed and Google Scholar. Studies included those examining rhBMP-2 specifically in spinal fusion contexts, excluding other bone morphogenetic proteins (BMPs) and non-spinal applications. This review presents an overarching synopsis of rhBMP-2, its development history and clinical efficacy, the emergence of side effects, and evolving patterns of clinical use. As discussed in this review, clinical practice has adjusted usage and dosages to mitigate adverse effects, yet the need for safer delivery mechanisms persists. rhBMP-2 remains a potent osteoinductive agent with comparable fusion success, as measured by radiographic fusion and good clinical outcomes, to autologous grafts but poses unique risks. This review sets out how further research is essential to optimise the delivery of rhBMP-2 to reduce side effects. Enhanced understanding and innovation of spatio-temporal presentation relative to endogenous BMP could significantly improve patient outcomes in spinal fusion surgeries. The review contributes to the growing body of literature on the use of rhBMP-2 in spine surgery and discusses changing patterns of clinical use over time.

Reconstruction of craniomaxillofacial bone defects using 3D-printed hydroxyapatite (HA) bioceramic patient-specific implants (PSIs) is a new technique with great potential. This study aimed to investigate the advantages, disadvantages, and clinical outcomes of these implants in craniomaxillofacial surgeries. The PubMed and Embase databases were searched for patients with craniomaxillofacial bone defects treated with bioceramic PSIs. Clinical outcomes such as biocompatibility, biomechanical properties, and aesthetics were evaluated and compared to those of commonly used titanium or poly-ether-ether-ketone (PEEK) implants and autologous bone grafts. Two clinical cases are presented to illustrate the surgical procedure and clinical outcomes of HA bioceramic PSIs. Literature review showed better a biocompatibility of HA PSIs than titanium and PEEK. The initial biomechanical properties were inferior to those of autologous bone grafts, PEEK, and titanium but improved when integrated. Satisfactory aesthetic results were found in our two clinical cases with good stability and absence of bone resorption or infection. Radiological signs of osteogenesis were observed in the two clinical cases six months postoperatively. HA bioceramic PSIs have excellent biocompatible properties and imitate natural bone biomechanically and radiologically. They are a well-suited alternative for conventional biomaterials in the reconstruction of load-sharing bone defects in the craniomaxillofacial region.

UNASSIGNED: Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla.
UNASSIGNED: Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool).
UNASSIGNED: Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): -0.01-0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): -1.24, 95% CI: -1.91- -0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: -0.02-0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: -0.14-0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes.
UNASSIGNED: This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

BACKGROUND: Cranioplasty corrects cranial bone defects using various bone substitutes or autologous bone flaps created during a previous craniectomy surgery. These autologous bone flaps can be preserved through subcutaneous preservation (SP) or cryopreservation (CP).
OBJECTIVE: We aim to compare outcomes and complications for both SP and CP techniques to enhance the current evidence about autologous bone flap preservation.
METHODS: Five electronic databases were searched to collect all relevant studies. Records were screened for eligibility. Data were extracted from the included studies independently. We categorized surgical site infection (SSI) as either due to Traumatic brain injury (TBI) or not to reveal potential variations in SSI incidence. The double-arm meta-analysis utilized risk ratios (RR) and mean differences (MD) with corresponding confidence intervals (CI) to pool categorical and continuous outcomes, respectively. Proportions with their respective 95% CIs were pooled for single-arm meta-analyses to determine outcomes related to SP technique.
RESULTS: Seventeen studies involving 1169 patients were analyzed. No significant difference in SSI rates was observed between SP and CP methods in patients with or without TBI. SP was linked to shorter hospital stays in two studies (194 patients). Single-arm analysis showed a 17% revision surgery rate across five studies (375 patients) and infection rates in 17 studies for SP. New bone formation occurred in 13.2% of patients, with 19.9% showing resorption.
CONCLUSIONS: SP and CP methods showed similar SSI rates post-craniectomy in TBI and non-TBI patients. SP was associated with reduced hospitalization time, low infection rates, and a moderate need for revision surgery.

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.

BACKGROUND: Patients with dysplastic bone diseases, including fibrous dysplasia (FD), represent a particular challenge for placement of dental implants. This is due to structural bony changes that may compromise the bone blood supply and plasticity, thus potentially affecting the process of osseointegration. This case report describes a novel approach for dental-implant-based rehabilitation of the posterior maxilla affected by craniofacial fibrous dysplasia (CFD), with 7 years of treatment follow-up.
METHODS: A 35-year-old female patient was referred due to a suspected unidentified bone lesion affecting the left side of the maxilla. A clinical and radiographic diagnosis of fibrous dysplasia was confirmed through a wedge bone biopsy. Particulate bone substitute was packed into a box-shaped ostectomy area of the lesion in the affected maxillary alveolar ridge. This was followed by the placement of four implants 6 months post operation. The implants were successfully integrated, as confirmed by clinical examination over 7 years of follow up.
CONCLUSIONS: this treatment approach may be considered as a predictable and efficient treatment modality for dental implant rehabilitation in patients with a variety of fibro-osseous lesions, including fibrous dysplasia, which affect the alveolar bone.

OBJECTIVE: Bone augmentation techniques show a relatively high complication rate, which might be due to graft non-union and resorption. It is unclear which augmentation techniques demonstrate the highest amount of non-union and resorption and whether this leads to worse clinical or functional outcomes. Therefore, the aim of this review was (i) to compare non-union and resorption rates between surgical approaches, procedures, graft types, donor sites and fixation methods regarding clinical and functional outcomes and (ii) determine whether high non-union or resorption rates lead to less favorable clinical or functional outcomes.
METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements were followed. PubMed, EMBASE (Ovid) and Cochrane Library were searched on December 15th 2021 for studies examining bone graft non-union or resorption using radiograph or CT following glenoid augmentation to treat anterior shoulder dislocation.
RESULTS: The search resulted in 103 inclusions, comprising 5,128 glenoid augmentations. When comparing pooled proportions of bony union, graft fracture rate, hardware failure rate, recurrence rate, return to sports and Rowe score, most results were similar between approaches, procedures, graft types, donor sites and fixation methods. High resorption rates were seen for allograft augmentation (74.3; 95% CI: 39.8-92.7) compared to autograft augmentation (15.5; 95% CI 10.1-23.2), but this was not associated with higher recurrence rates or worse clinical outcomes. Meta-analyses (8 studies; 494 patients) demonstrated no difference in incomplete and complete non-union rates between arthroscopic and open procedures; however, both analyses showed substantial heterogeneity. Higher partial resorption rates were observed on CT (48.0; 95% CI 43.3-52.7) compared to radiograph (14.1; 95% CI 10.9-18.1). Three studies comprising 267 shoulders demonstrated a higher rate of non-union and recurrence in smokers, whereas one study comprising 38 shoulders did not.
CONCLUSIONS: Non-union and resorption rates were similar among procedures, grafts and fixation methods. Higher resorption rates were observed in allografts, but this was not associated with higher recurrence rates or worse clinical outcomes. Pooling data demonstrated substantial heterogeneity and definitions varied among studies, warranting more standardized measuring.
METHODS: IV.

A large variety of biomaterials, biologics and membranes have been utilized in the past 40 years for the regenerative treatment of periodontal infrabony defects. Biologic agents have progressively gained popularity among clinicians and are routinely used for periodontal regeneration. In alignment with the goals of the American Academy of Periodontology (AAP) Best Evidence Consensus (BEC) on the use of biologic mediators in contemporary clinical practice, the aim of this sytematic review was to evaluate the effect of biologic agents, specifically autogenous blood-dervied products (ABPs), enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB), on the regenerative outcomes of infrabony defects.
A detailed systematic search was conducted to identify eligible randomized control trials (RCTs) reporting the outcomes of periodontal regenerative therapy using biologics for the treatment of infrabony defects. A frequentist mixed-modeling approach to network meta-analysis (NMA), characterized by the assessment of three individual components for the treatment of an infrabony defect (the bone graft material [BG], the biologic agent, the application of a barrier membrane) was performed to evaluate and compare the relative efficacy of the different components, on the outcomes of different therapeutic modalities of periodontal regeneration.
A total of 153 eligible RCTs were included, with 150 studies contributing to the NMA. The quantitative analysis showed that the addition of biologic agents to bone graft significantly improves the clinical and radiographic outcomes, as compared to BG and flap procedures alone. Barrier membranes enhanced the regenerative outcomes of BG but did not provide further benefits in combination with biologics. The type of BG (autogenous, allogeneic, xenogeneic or alloplastic) and the biologic agent (EMD, platelet-rich fibrin [PRF], platelet-rich plasma [PRP] or rhPDGF-BB) played a significant role on the final outcomes of infrabony defects. Allogeneic and xenogeneic BGs exhibited statistically significantly superior clinical gain than synthetic and autogenous BGs (p < 0.05 in all the comparisons), while rhPDGF-BB and PRF demonstrated significantly higher stability of the gingival margin (p < 0.01) and radiographic bone fill/gain (p < 0.05), together with greater, although not statistically significant, clinical attachment level gain and pocket depth reduction, than EMD and PRP. Overall, rhPDGF-BB exhibited the largest effect size for most parameters, including clinical attachment level gain, pocket depth reduction, less gingival recession and radiographic linear bone gain. Considering the relatively high number of trials presenting an unclear or high risk of bias, the strength of recommendation supporting the use of PRP was judged weak, while the recommendation for EMD, PRF and rhPDGF-BB was deemed in favor.
Biologics enhance the outcomes of periodontal regenerative therapy. Combination therapies involving BGs + biologics or BGs + barrier membrane demonstrated to be superior to monotherapies. The choice of the type of BG and biologic agent seems to have significant impact on the clinical and radiographic outcomes of infrabony defects.

Periodontal infections are noncommunicable chronic inflammatory diseases of multifactorial origin that can induce destruction of both soft and hard tissues of the periodontium. The standard remedial modalities for periodontal regeneration include nonsurgical followed by surgical therapy with the adjunctive use of various biomaterials to achieve restoration of the lost tissues. Lately, there has been substantial development in the field of biomaterial, which includes the sole or combined use of osseous grafts, barrier membranes, growth factors and autogenic substitutes to achieve tissue and bone regeneration. Of these, bone replacement grafts have been widely explored for their osteogenic potential with varied outcomes. Osseous grafts are derived from either human, bovine or synthetic sources. Though the biologic response from autogenic biomaterials may be better, the use of bone replacement synthetic substitutes could be practical for clinical practice. This comprehensive review focuses initially on bone graft replacement substitutes, namely ceramic-based (calcium phosphate derivatives, bioactive glass) and autologous platelet concentrates, which assist in alveolar bone regeneration. Further literature compilations emphasize the innovations of biomaterials used as bone substitutes, barrier membranes and complex scaffold fabrication techniques that can mimic the histologically vital tissues required for the regeneration of periodontal apparatus.

OBJECTIVE: The purpose of this meta-analysis was to compare implant survival in irradiated and non-irradiated bone and to investigate potential risk factors for implant therapy in oral cancer patients.
METHODS: An extensive search in the electronic databases of the National Library of Medicine was performed. Systematic review and meta-analysis were conducted according to PRISMA statement. The meta-analysis was performed for studies with a mean follow-up of at least three and five years, respectively.
RESULTS: The systematic review resulted in a mean overall implant survival of 87.8% (34%-100%). The meta-analysis revealed a significantly higher rate of implant failure in irradiated bone compared to non-irradiated bone (p < .00001, OR 1.97, CI [1.63, 2.37]). The studies also showed that implants placed into irradiated grafted bone were more likely to fail than those in irradiated native bone (p < .0001, OR 2.26, CI [1.50, 3.40]).
CONCLUSIONS: Even though overall implant survival was high, radiotherapy proves to be a significant risk factor for implant loss. Augmentation procedures may also increase the risk of an adverse outcome, especially in combination with radiotherapy.
CONCLUSIONS: The treatment of patients receiving radiotherapy of any form requires precise individual planning and a close aftercare. Implants should be placed in local bone rather than in bone grafts, if possible.