Lateral Bone Augmentation Using a Three-Dimensional-Printed Polymeric Chamber to Compare Biomaterials.

The aim of this study was to test the suitability of calcium phosphate cement mixed with poly(lactic-co-glycolic acid) (CPC-PLGA) microparticles into a ring-shaped polymeric space-maintaining device as bone graft material for lateral bone augmentation. Therefore, the bone chambers were installed on the lateral portion of the anterior region of the mandibular body of mini-pigs. Chambers were filled with either CPC-PLGA or BioOss® particles for comparison and left for 4 and 12 weeks. Histology and histomorphometry were used to obtain temporal insight in material degradation and bone formation. Results indicated that between 4 and 12 weeks of implantation, a significant degradation of the CPC-PLGA (from 75.1% to 23.1%), as well as BioOss material, occurred (from 40.6% to 14.4%). Degradation of both materials was associated with the presence of macrophage-like and osteoclast-like cells. Furthermore, a significant increase in bone formation occurred between 4 and 12 weeks for the CPC-PLGA (from 0.1% to 7.2%), as well as BioOss material (from 8.3% to 23.3%). Statistical analysis showed that bone formation had progressed significantly better using BioOss compared to CPC-PLGA (p < 0.05). In conclusion, this mini-pig study showed that CPC-PLGA does not stimulate lateral bone augmentation using a bone chamber device. Both treatments failed to achieve "clinically" meaningful alveolar ridge augmentation.

Influence of bisphosphonate treatment on bone substitute performance in osteoporotic conditions.

OBJECTIVE: Considering the elevated number of osteoporotic patients in need of bone graft procedures, we here evaluated the effect of alendronate (ALN) treatment on the regeneration of bone defects in osteoporotic rats. Bone formation was histologically and histomorphometrically assessed in rat femoral condyle bone defects filled with bone graft (Bio-Oss®) or left empty. METHODS: Male Wistar rats were induced osteoporotic through orchidectomy (ORX) and SHAM-operated. The animals were divided into three groups: osteoporotic (ORX), osteoporotic treated with ALN (ORX + ALN) and healthy (SHAM). Six weeks after ORX or SHAM surgeries, bone defects were created bilaterally in femoral condyles; one defect was filled with Bio-Oss® and the other one left empty. Bone regeneration within the defects was analyzed by histology and histomorphometry after 4 and 12 weeks. RESULTS: Histological samples showed new bone surrounding Bio-Oss® particles from week 4 onward in all three groups. At week 12, the data further showed that ALN treatment of osteoporotic animals enhanced bone formation to a 10-fold increase compared to non-treated osteoporotic control. Bio-Oss® filling of the defects promoted bone formation at both implantation periods compared to empty controls. CONCLUSION: Our histological and histomorphometric results demonstrate that the enteral administration of alendronate under osteoporotic bone conditions leverages bone defect regeneration to a level comparable to that in healthy bone. Additionally, Bio-Oss® is an effective bone substitute, increasing bone formation, and acting as an osteoconductive scaffold guiding bone growth in both healthy and osteoporotic bone conditions. SIGNIFICANCE: Based on the results of this study, enteral use of ALN mitigates adverse effects of an osteoporotic condition on bone defect regeneration.

Repeated Application and Removal of Polyisocyanopeptide Hydrogel Wound Dressings in a Splinted Full-Thickness Wound Model.

Polyisocyanopeptide (PIC) hydrogels are proposed as promising wound dressings. These gels are thermo-sensitive, allow application as a cold liquid, and rely on gelation through body heat. It is supposed that the gel can be easily removed by reversing the gelation and washing it away with a cold irrigation solution. The impact on wound healing of the regular application and removal of PIC dressings is compared to a single application of PIC and the clinically used Tegaderm™ in murine splinted full-thickness wounds for up to 14 days. SPECT/CT analysis of 111In-labelled PIC gels showed that, on average, 58% of the PIC gel could be washed out of the wounds with the employed method, which is, however, heavily influenced by personal technique. Evaluation with photography and (immuno-)histology showed that wounds in which PIC dressings were regularly removed and replaced were smaller at 14 days post-injury but performed on par with the control treatment. Moreover, the encapsulation of PIC in wound tissue was less severe and occurred less often when PIC was regularly refreshed. In addition, no morphological damage related to the removal procedure was observed. Thus, PIC gels are atraumatic and perform similarly to currently employed wound dressing materials, offering possible future benefits for both clinicians and patients.

Repair of complex ovine segmental mandibulectomy utilizing customized tissue engineered bony flaps.

Craniofacial defects require a treatment approach that provides both robust tissues to withstand the forces of mastication and high geometric fidelity that allows restoration of facial architecture. When the surrounding soft tissue is compromised either through lack of quantity (insufficient soft tissue to enclose a graft) or quality (insufficient vascularity or inducible cells), a vascularized construct is needed for reconstruction. Tissue engineering using customized 3D printed bioreactors enables the generation of mechanically robust, vascularized bony tissues of the desired geometry. While this approach has been shown to be effective when utilized for reconstruction of non-load bearing ovine angular defects and partial segmental defects, the two-stage approach to mandibular reconstruction requires testing in a large, load-bearing defect. In this study, 5 sheep underwent bioreactor implantation and the creation of a load-bearing mandibular defect. Two bioreactor geometries were tested: a larger complex bioreactor with a central groove, and a smaller rectangular bioreactor that were filled with a mix of xenograft and autograft (initial bone volume/total volume BV/TV of 31.8 ± 1.6%). At transfer, the tissues generated within large and small bioreactors were composed of a mix of lamellar and woven bone and had BV/TV of 55.3 ± 2.6% and 59.2 ± 6.3%, respectively. After transfer of the large bioreactors to the mandibular defect, the bioreactor tissues continued to remodel, reaching a final BV/TV of 64.5 ± 6.2%. Despite recalcitrant infections, viable osteoblasts were seen within the transferred tissues to the mandibular site at the end of the study, suggesting that a vascularized customized bony flap is a potentially effective reconstructive strategy when combined with an optimal stabilization strategy and local antibiotic delivery prior to development of a deep-seated infection.

Fast Degradable Calcium Phosphate Cement for Maxillofacial Bone Regeneration.

The aim of this preclinical study was to test the applicability of calcium phosphate cement (CPC)-poly(lactic-co-glycolic acid) (PLGA)-carboxymethylcellulose (CMC) as a bone substitute material for guided bone regeneration (GBR) procedures in a clinically relevant mandibular defect model in minipigs. In the study, a predicate device (i.e., BioOss®) was included for comparison. Critical-sized circular mandibular bone defects were created and filled with either CPC-PLGA-CMC without coverage with a GBR membrane or BioOss covered with a GBR membrane and left to heal for 4 and 12 weeks to obtain temporal insight in material degradation and bone formation. Bone formation increased significantly for both CPC-PLGA-CMC and BioOss with increasing implantation time. Further, no significant differences were found for bone formation at either 4 or 12 weeks between CPC-PLGA-CMC and BioOss. Finally, bone substitute material degradation increased significantly for both CPC-PLGA-CMC and BioOss from 4 to 12 weeks of implantation, showing the highest degradation for CPC-PLGA-CMC (∼85%) compared to BioOss (∼12%). In conclusion, this minipig study showed that CPC-PLGA-CMC can be used as a bone-grafting material and stimulates bone regeneration to a comparable extent as with BioOss particles. Importantly, CPC-PLGA-CMC degrades faster compared to BioOss, is easier to apply into a bone defect, and does not need the use of an additional GBR membrane. Consequently, the data support the further investigation of CPC-PLGA-CMC in human clinical trials. Impact statement Guided bone regeneration (GBR) is a frequently used dental surgical technique to regenerate the alveolar ridge to allow stable implant installation. However, stabilization of the GBR membrane and avoidance of bone graft movement remain a challenge. Consequently, there is need for the development of alternative materials to be used in GBR procedures that are easier to apply and induce predictable bone regeneration. In this minipig study, we focused on the applicability of calcium phosphate cement-poly(lactic-co-glycolic acid)-carboxymethylcellulose as an alternative bone substitute material for GBR procedures without the need of an additional GBR membrane.

A Mini-Pig Mandibular Defect Model for Evaluation of Craniomaxillofacial Bone Regeneration.

Craniomaxillofacial bone defects represent a clinical challenge in the fields of maxillofacial surgery and (implant) dentistry. Regeneration of these bone defects requires the application of bone graft materials that facilitate new bone formation in a safe, reliable, and predictive manner. In addition to autologous bone graft, several types of (synthetic) bone substitute materials have become clinically available, and still major efforts are focused on improving such bone substitute materials by optimizing their properties. Given the regulatory necessity to evaluate the performance of new bone substitute materials for craniomaxillofacial bone regeneration in a large animal model with similarity to human bone before clinical application, we here describe a mini-pig mandibular bone defect model that allows for the creation of multiple (critical-size) bone defects within the mandibular body of a single animal. As examples of bone substitute materials, we utilize both the clinically used BioOss granules and an experimental calcium phosphate cement for filling the created defects. Regarding the latter, its advantages are the injectable application within the defect site, in which the material rapidly sets, and the tailorable degradation properties via the inclusion of hydrolytically degrading polymeric particles. For both bone substitute materials, we show the suitability of the bone defect model to assess bone regeneration via histology and micro-computed tomography. Impact statement Given the regulatory necessity to evaluate the performance of new bone substitute materials for craniomaxillofacial bone regeneration in a large animal model with similarity to the human bone before clinical application, we here describe a mini-pig mandibular bone defect model that allows for the creation of multiple (critical-size) bone defects within the mandibular body of a single animal that can be used for the evaluation of the bone regenerative capacity of new bone grafting materials as well as tissue-engineered products for alveolar bone regeneration.

Histological evaluation of titanium fiber mesh-coated implants in a rabbit femoral condyle model.

OBJECTIVES: This study was aimed to comparatively evaluate new bone formation into the pores of a flexible titanium fiber mesh (TFM) applied on the surface of implant. METHODS: Twenty-eight custom made cylindrical titanium implants (4 ×10 mm) with and without a layer of two different types of TFM (fiber diameter of 22 µm and 50 µm, volumetric porosity ~70%) were manufactured and installed bilaterally in the femoral condyles of 14 rabbits. The elastic modulus for these two TFM types was ~20 GPa and ~5 GPa respectively, whereas the solid titanium was ~110 GPa. The implants (Control, TFM-22, TFM-50) were retrieved after 14 weeks of healing and prepared for histological assessment. The percentage of the bone area (BA%), the bone-to-implant contact (BIC%) and amount were determined. RESULTS: Newly formed bone into mesh porosity was observed for all three types of implants. Histomorphometric analyses revealed significantly higher (~2.5 fold) BA% values for TFM-22 implants (30.9 ± 9.5%) compared to Control implants (12.7 ± 6.0%), whereas BA% for TMF-50 did not significantly differ compared with Control implants. Furthermore, both TFM-22 and TFM-50 implants showed significantly higher BIC% values (64.9 ± 14.0%, ~2.5 fold; 47.1 ± 14.1%, ~2 fold) compared to Control (23.6 ± 17.4%). Finally, TFM-22 implants showed more and thicker trabeculae in the peri-implant region. SIGNIFICANCE: This in vivo study demonstrated that implants with a flexible coating of TFM improve bone formation within the inter-fiber space and the peri-implant region.

Innovative implant design for continuous implant stability: A mechanical and histological experimental study in the iliac crest of goats.

OBJECTIVES: this in vivo study reports on mechanical torque data as well as the biological evaluation up to 6 weeks after placement of implants with a unique wide knife thread design in a goat iliac crest model. We hypothesized that implants with this thread design would show substantial primary stability at a continuous level toward secondary stability. METHODS: 64 MegaGen Anyridge® implants were used with diameters 3.5 mm, 4.0 mm, 5.0 mm and 6.0 mm (n = 8). Implants were placed monocortically in the iliac crest of 16 healthy female Saanen goats, both on the right (for torque measurements) and left side (for histology/-morphometry). Torque-in at implant installation and torque-out at 2 and 6 weeks of implantation was measured, as well as bone-to-implant contact (BIC) and bone-area between the screw threads (BA). RESULTS: Histology showed intimate bone-to-implant contact with a maturating trabecular structure between 2 and 6 weeks. Torque values showed a dependency on implant diameter. For all implant diameters, torque-in values were similar to torque-out values at 2 weeks. At 6 weeks however, all torque-out values were significantly increased. BIC and BA percentages showed similar values for all diameters at both 2 and 6 weeks. CONCLUSIONS: These results prove the absence of a lag-phase in implant stability for MegaGen Anyridge® implants in the goat iliac crest model. The increased torque-out values at 6 weeks without increasing BIC and BA percentages correlate with the observed maturation of bone-to-implant contact quality over time. CLINICAL SIGNIFICANCE: It is a challenge to optimize implants with continuous primary stability and rapid transition into secondary stability to minimize the duration of the lag-phase. The results of this study prove the absence of a lag-phase in implant stability for MegaGen Anyridge® implants. Consequently, the data from this work are important for the treatment of individual patients 'translating' these findings into clinical implant procedures.

Regenerating Critical Size Rat Segmental Bone Defects with a Self-Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP-2 Incorporation.

The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HABP -CaP) or hydrogel loaded with BMP-2 in two dosages (HABP -CaP-lowBMP2 or HABP -CaP-highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X-ray examination, micro-CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HABP -CaP gel alone. Loading of the HABP -CaP gel with low dose BMP-2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP-2 loading of the HABP -CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.

Electrophoretic deposition of silk fibroin coatings with pre-defined architecture to facilitate precise control over drug delivery.

The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved Bombyx mori SF (bmSF) molecules and pre-made bmSF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising Antheraea pernyi SF (apSF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved bmSF molecules or pre-loaded into pre-made bmSF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich apSF top-layer improved cell adhesion, spreading and proliferation compared with bmSF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery.

Bilayered, peptide-biofunctionalized hydrogels for in vivo osteochondral tissue repair.

Osteochondral defects present a unique clinical challenge due to their combination of phenotypically distinct cartilage and bone, which require specific, stratified biochemical cues for tissue regeneration. Furthermore, the articular cartilage exhibits significantly worse regeneration than bone due to its largely acellular and avascular nature, prompting significant demand for regenerative therapies. To address these clinical challenges, we have developed a bilayered, modular hydrogel system that enables the click functionalization of cartilage- and bone-specific biochemical cues to each layer. In this system, the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) was click conjugated with either a cartilage- or bone-specific peptide sequence of interest, and then mixed with a suspension of thermoresponsive polymer and mesenchymal stem cells (MSCs) to generate tissue-specific, cell-encapsulated hydrogel layers targeting the cartilage or bone. We implanted bilayered hydrogels in rabbit femoral condyle defects and investigated the effects of tissue-specific peptide presentation and cell encapsulation on osteochondral tissue repair. After 12 weeks implantation, hydrogels with a chondrogenic peptide sequence produced higher histological measures of overall defect filling, cartilage surface regularity, glycosaminoglycan (GAG)/cell content of neocartilage and adjacent cartilage, and bone filling and bonding compared to non-chondrogenic hydrogels. Furthermore, MSC encapsulation promoted greater histological measures of overall defect filling, cartilage thickness, GAG/cell content of neocartilage, and bone filling. Our results establish the utility of this click functionalized hydrogel system for in vivo repair of the osteochondral unit. STATEMENT OF SIGNIFICANCE: Osteochondral repair requires mimicry of both cartilage- and bone-specific biochemical cues, which are highly distinct. While traditional constructs for osteochondral repair have mimicked gross compositional differences between the cartilage and bone in mineral content, mechanical properties, proteins, or cell types, few constructs have recapitulated the specific biochemical cues responsible for the differential development of cartilage and bone. In this study, click biofunctionalized, bilayered hydrogels produced stratified presentation of developmentally inspired peptide sequences for chondrogenesis and osteogenesis. This work represents, to the authors' knowledge, the first application of bioconjugation chemistry for the simultaneous repair of bone and cartilage tissue. The conjugation of tissue-specific peptide sequences successfully promoted development of both cartilage and bone tissues in vivo.

Application of specialized pro-resolving mediators in periodontitis and peri-implantitis: a review.

Scaling and root planning is a key element in the mechanical therapy used for the eradication of biofilm, which is the major etiological factor for periodontitis and peri-implantitis. However, periodontitis is also a host mediated disease, therefore, removal of the biofilm without adjunctive therapy may not achieve the desired clinical outcome due to persistent activation of the innate and adaptive immune cells. Most recently, even the resident cells of the periodontium, including periodontal ligament fibroblasts, have been shown to produce several inflammatory factors in response to bacterial challenge. With increased understanding of the pathophysiology of periodontitis, more research is focusing on opposing excessive inflammation with specialized pro-resolving mediators (SPMs). This review article covers the major limitations of current standards of care for periodontitis and peri-implantitis, and it highlights recent advances and prospects of SPMs in the context of tissue reconstruction and regeneration. Here, we focus primarily on the role of SPMs in restoring tissue homeostasis after periodontal infection.

The molecular conformation of silk fibroin regulates osteogenic cell behavior by modulating the stability of the adsorbed protein-material interface.

Silk fibroin (SF) can be used to construct various stiff material interfaces to support bone formation. An essential preparatory step is to partially transform SF molecules from random coils to ß-sheets to render the material water insoluble. However, the influence of the SF conformation on osteogenic cell behavior at the material interface remains unknown. Herein, three stiff SF substrates were prepared by varying the ß-sheet content (high, medium, and low). The substrates had a comparable chemical composition, surface topography, and wettability. When adsorbed fibronectin was used as a model cellular adhesive protein, the stability of the adsorbed protein-material interface, in terms of the surface stability of the SF substrates and the accompanying fibronectin detachment resistance, increased with the increasing ß-sheet content of the SF substrates. Furthermore, (i) larger areas of cytoskeleton-associated focal adhesions, (ii) higher orders of cytoskeletal organization and (iii) more elongated cell spreading were observed for bone marrow-derived mesenchymal stromal cells (BMSCs) cultured on SF substrates with high vs. low ß-sheet contents, along with enhanced nuclear translocation and activation of YAP/TAZ and RUNX2. Consequently, osteogenic differentiation of BMSCs was stimulated on high ß-sheet substrates. These results indicated that the ß-sheet content influences osteogenic differentiation of BMSCs on SF materials in vitro by modulating the stability of the adsorbed protein-material interface, which proceeds via protein-focal adhesion-cytoskeleton links and subsequent intracellular mechanotransduction. Our findings emphasize the role of the stability of the adsorbed protein-material interface in cellular mechanotransduction and the perception of stiff SF substrates with different ß-sheet contents, which should not be overlooked when engineering stiff biomaterials.

Histological and Histomorphometric Analyses of Bone Regeneration in Osteoporotic Rats Using a Xenograft Material.

We evaluated the effect of osteoporotic induction after eight weeks of initial healing of bone defects grafted with a xenograft material in a rat model. Bone defects were created in the femoral condyles of 16 female Wistar rats (one defect per rat). The defects were filled with bovine bone (Inter-Oss) granules. After eight weeks of bone healing, rats were randomly ovariectomized (OVX) or sham-operated (SHAM). At 14 weeks of bone healing, all animals were euthanized. Bone specimens were harvested and processed for histological and histomorphometric analyses to assess new bone formation (N-BF%), remaining bone graft (RBG%) and trabecular bone space (Tb.Sp%) within the defect area. After 14 weeks of bone healing, histological evaluation revealed a significant alteration in trabecular bone in OVX rats compared to SHAM rats. There was lower N-BF% in OVX rats (22.5% ± 3.0%) compared to SHAM rats (37.7% ± 7.9%; p < 0.05). Additionally, the RBG% was significantly lower in OVX (23.7% ± 5.8%) compared to SHAM (34.8% ± 9.6%; p < 0.05) rats. Finally, the Tb.Sp% was higher in OVX (53.8% ± 7.7%) compared to SHAM (27.5% ± 14.3%; p < 0.05) rats. In conclusion, within the limitations of this study, inducing an osteoporotic condition in a rat model negatively influenced bone regeneration in the created bone defect and grafted with a xenograft material.

Impact of Single or Combined Drug Therapy on Bone Regeneration in Healthy and Osteoporotic Rats.

Complications in bone regeneration in patients with systemic impaired bone metabolism (e.g., osteoporosis) represent a rapidly increasing clinical challenge. Alendronate and simvastatin are drugs commonly used to promote bone metabolism in osteoporotic conditions. The aim of this study was to evaluate initial bone regeneration within osseous defects grafted with beta-tricalcium phosphate (ß-TCP) in adjunction with systemic coadministrations of alendronate and simvastatin (i.e., daily subcutaneous injection for 3 weeks) in healthy and osteoporotic rats. Eighty Wistar female rats were ovariectomized (OVX; n = 40) or sham operated (n = 40). Six weeks later, osseous defects (a 3-mm critical-sized defect) were created in the left femoral condyles and then grafted with ß-TCP. From the day following graft installation, OVX and sham animals received for 3 weeks a daily subcutaneous injection of alendronate (50 µg/kg of body weight) and simvastatin (5 mg/kg of body weight), alone or in combination. A control group was included, which received subcutaneous saline administration. At the end of the 3 weeks, rats were euthanized and specimens (femoral condyles) were retrieved for histological evaluation and histomorphometric measurements, that is, bone area (BA%) and remaining bone graft (RBG%). In osteoporotic rats, 3 weeks of daily subcutaneous injection of combined therapy (alendronate plus simvastatin) led to a significant (p < 0.05) increase in BA% and a significant decrease in RBG% compared to healthy controls in osseous defects grafted with ß-TCP (BA%: 28.6 ± 12.0 vs. 18.2 ± 7.6, RBG% 61.3 ± 11.1 vs. 70.7 ± 7.3). No significant differences in BA% and RBG% were found in the OVX rats for single treatments. Furthermore, healthy controls showed similar BA% and RBG% upon single or combined therapy compared to nontreated control rats. Daily coinjections (for 3 weeks) of alendronate plus simvastatin result in a significant enhancement of bone regeneration within osseous defects grafted with ß-TCP in osteoporotic rats. Despite the expected effects on osteoporotic bone, our study did not confirm the hypothesized benefit of alendronate and simvastatin on bone regeneration in osseous defects in healthy conditions. The efficacy of the combination drug therapy on bone regeneration demands further investigation to elucidate molecular and cellular aspects underlying this therapy.

The effect of lipoxin A4 on E. coli LPS-induced osteoclastogenesis.

OBJECTIVES: The objective of the present study was to investigate the effect of lipoxin-type A4 (LXA4) on bacterial-induced osteoclastogenesis. MATERIAL AND METHODS: Human periodontal ligament cells (PDLCs) in coculture with osteoclast precursors (RAW264.7 cells) were exposed to bacterial stimulation with lipopolysaccharide (LPS) to induce inflammation. After 24 h, cells were treated to 100 ng/ml of LXA4 and 50 ng/ml of forymul peptide receptor 2 (FPR2/ALX) receptor antagonist (Boc-2). After 5 days, osteoclastic resorptive activity was assessed on calcium phosphate (CaP) synthetic bone substitute. Additionally, osteoclastic differentiation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP enzymatic activity assay, and on the expression of osteoclast-specific genes. RESULTS: We found that stimulation of in the osteoclasts with LPS-stimulated PDLCs induced a significant increase in tartrate-resistant acid phosphatase (TRAP) positive cells, higher resorptive activity, and enhanced expression of specific genes. Meanwhile, LXA4-treatment exhibited strong anti-inflammatory activity, and was able to reverse these inflammatory effects. CONCLUSIONS: We conclude that (1) PDLCs are a potential target for treating bacterial-induced bone resorption in patients with periodontal disease, and (2) LXA4 is a suitable candidate for such therapy. CLINICAL RELEVANCE: The results prove that lipoxins have a protective role in bacterial-induced periodontal inflammation and alveolar bone resorption, which can be translated into a clinical beneficial alterative treatment.