The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - β-tricalcium phosphate (β-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.

BACKGROUND: Calcium hydroxylapatite (CaHA) dermal filler is used for a variety of aesthetic treatments; however, the safety and effectiveness of diluted CaHA for the treatment of décolleté wrinkles have not been established.
OBJECTIVE: To demonstrate the effectiveness and safety of diluted CaHA (Radiesse; 1:2 CaHA:saline) injection for the improvement of décolleté wrinkles in females.
METHODS: Eligible females with moderate or severe ratings on the Merz Aesthetic Scale (MAS) Decollete Wrinkles - At Rest received up to 3 injection cycles of diluted CaHA either 8 weeks apart (3 injection cycles) or 16 weeks apart (2 injection cycles). Effectiveness was evaluated by improvement on the MAS. Adverse events were recorded over a 52 week period.
RESULTS: Sixteen weeks after the last treatment, the response rate (1-point improvement or greater) on the MAS Decollete Wrinkles - At Rest was 73.5% (P<0.0001; pooled sample) for all patients. The use of diluted CaHA in the decollete also demonstrated a favorable safety profile.
CONCLUSIONS: Diluted CaHA is a safe and effective treatment for the improvement of decollete wrinkles in females.J Drugs Dermatol. 2024;23(7):551-556.  doi:10.36849/JDD.8261.

BACKGROUND: This study evaluated the clinical benefits of adding NanoBone® with split-crest technique and simultaneous implant placement covered with platelet-rich fibrin membrane in horizontally deficient maxillary ridges in terms of crestal and horizontal bone changes and patient morbidity.
METHODS: Forty patients indicated for maxillary ridge splitting and simultaneous implant placement were assigned randomly to the study groups: control group (Platelet Rich Fibrin membrane) and test group (Platelet Rich Fibrin membrane + Nanobone®). The Cone Beam Computed Tomography Fusion technique was utilized to assess crestal and horizontal bone changes after five months of the surgical procedure. Patient morbidity was recorded for one week post-surgical.
RESULTS: Five months post-surgical, buccal crestal bone resorption was 1.26 ± 0.58 mm for the control group and 1.14 ± 0.63 mm for the test group. Lingual crestal bone resorption was 1.40 ± 0.66 mm for the control group and 1.47 ± 0.68 mm for the test group. Horizontal bone width gain was 1.46 ± 0.44 mm for the control group and 1.29 ± 0.73 mm for the test group. There was no significant statistical difference between study groups regarding crestal and horizontal bone changes and patient morbidity.
CONCLUSIONS: The tomographic assessment of NanoBone® addition in this study resulted in no statistically significant difference between study groups regarding crestal and horizontal bone changes and patient morbidity. More randomized controlled clinical trials on gap fill comparing different bone grafting materials versus no grafting should be conducted.
RESULTS:
UNASSIGNED: NCT02836678, 13th January 2017.

OBJECTIVE: This study evaluated the implant stability, volumetric changes, and patient-reported outcome measures (PROMs) of hydroxyapatite (HA) nano-coated sandblasted/acid-etched (SLA) implants compared to uncoated SLA implants.
METHODS: Forty patients were recruited and randomly allocated to HA nano-coated SLA group (test, n = 20) and uncoated SLA group (control, n = 20) using single-blinded/block randomization. Implants were immediately placed in maxillary posterior region using a digital surgical guide. Insertion torque and implant stability quotient (ISQ) were measured at implant surgery and 1, 2, 3, and 4 months postoperatively. Intraoral scans, PROMs and soft tissue inflammation data were collected, and multivariable linear regression analysis of ISQ was performed.
RESULTS: In total, 48 implants (test; n = 24, control; n = 24) in 37 patients (test; n = 19, control; n = 18) were analyzed. Despite no significant between-group difference at surgery, the test group showed higher ISQ values than the control group at 2 (76.53 ± 4.17 vs. 71.32 ± 4.79, p < 0.01), 3 (77.45 ± 4.41 vs. 73.85 ± 4.69, p < 0.05), and 4 months (79.08 ± 2.96 vs. 73.43 ± 3.52, p < 0.0001) postoperatively. There were no significant differences in linear and volumetric changes, PROMs, and soft tissue inflammation analysis between two groups. The ISQ at implant surgery was influenced by age and diabetes mellitus (DM) at the implant level and DM and predicted total bone-to-implant contact area at the patient level.
CONCLUSIONS: HA nano-coated SLA implants promoted favorable immediate implants stability during early osseointegration phase compared to uncoated SLA implants, but displayed similar dimensional changes, PROMs, and soft tissue inflammation outcomes.
BACKGROUND: Clinical Research Information Service (CRIS), KCT0006364. Registered 21 July 2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24221&search_page=L .

This study investigates the safety and efficacy of 3D-printed polycaprolactone/hydroxyapatite (PCL/HA) scaffolds for patient-specific cranioplasty surgeries, employing liquid deposition modeling (LDM) technology. This research is pioneering as it explores the impact of gamma radiation on PCL/HA scaffolds and utilizes printing ink with the highest content of HA known in the composite. The mechanical, morphological, and macromolecular stability of the gamma-sterilized scaffolds were verified before implantation. Subsequent research involving animal subjects was conducted to explore the effects of sterilized implants. Eventually, three clinical cases were selected for the implantation studies as part of a phase 1 non-randomized open-label clinical trial. It was shown that a 25 kGy gamma-ray dose for sterilizing the printed implants did not alter the required geometrical precision of the printed implants. The implants exhibited well-distributed HA and strength comparable to cancellous bone. Gamma radiation reduced hydrophobicity and water uptake capacity without inducing pyrogenic or inflammatory responses. Personalized PCL/HA substitutes successfully treated various craniomaxillofacial defects, including trauma-induced facial asymmetry and congenital deformities. HA nanoparticles in the ink stimulated significant osteoconductive responses within three months of implantation. Moreover, the results revealed that while larger implants may exhibit a slower bone formation response in comparison to smaller implants, they generally had an acceptable rate and volume of bone formation. This clinical trial suggests the application of a sterilized PCL/HA composite for craniomaxillofacial surgery is safe and could be considered as a substitute for autologous bone.

The objective of this study was to evaluate the synergistic effect of eggshell-derived nanohydroxyapatite (EnHA) and carboxymethyl chitosan (CMC) in remineralizing artificially induced dentinal lesions. EnHA and CMC were synthesized using simple chemical processes and characterized using FTIR, XRD, HRSEM-EDX, TEM, DLS and TGA/DTA analyses. A total of 64 pre-demineralized coronal dentin specimens were randomly subjected to following treatments (n = 16):artificial saliva (AS), EnHA, CMC, and EnHA-CMC, followed by pH cycling for 7 days. HRSEM-EDX, Vickers-indenter, and micro-Raman analyses were used to assess surface-topography, microhardness, and chemical analysis, respectively. All tested materials demonstrated non-cytotoxicity when assessed on hDPSCs using MTT assay. FTIR, XRD and thermal analyses confirmed the characteristics of both EnHA and CMC. EnHA showed irregular rod-shaped nanoparticles (30-70 nm) with the presence of Ca,P,Na, and Mg ions. Dentin treated with EnHA-CMC exhibited complete tubular occlusion and highest microhardness whereas the AS group revealed the least mineral deposits (p < 0.05). No significant differences were observed between EnHA and CMC groups (p > 0.05). In addition, molecular conformation analysis revealed peak intensities in collagen\'s polypeptide chains in dentin treated with CMC and EnHA-CMC, whereas other groups showed poor collagen stability. The results highlighted that EnHA-CMC aided in rapid and effective biomineralization, suggesting its potential as a therapeutic solution for treating dentin caries.

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

OBJECTIVE: To evaluate the adhesion of mono and duospecies biofilm on a commercially available dental implant surface coated with hydroxyapatite nanoparticles (nanoHA).
METHODS: Titanium discs were divided into two groups: double acid-etched (AE) and AE coated with nanoHA (NanoHA). Surface characteristics evaluated were morphology, topography, and wettability. Mono and duospecies biofilms of Streptococcus sanguinis (S. sanguinis) and Candida albicans (C. albicans) were formed. Discs were exposed to fetal bovine serum (FBS) to form the pellicle. Biofilm was growth in RPMI1640 medium with 10% FBS and 10% BHI medium for 6 h. Microbial viability was evaluated using colony-forming unit and metabolic activity by a colorimetric assay of the tetrazolium salt XTT. Biofilm architecture and organization were evaluated by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM).
RESULTS: AE surface had more pores, while NanoHA had even nanoHA crystals distribution. Roughness was similar (AE: 0.59 ± 0.07 µm, NanoHA: 0.69 ± 0.18 µm), but wettability was different (AE: Θw= 81.79 ± 8.55°, NanoHA: Θw= 53.26 ± 11.86°; P = 0.01). NanoHA had lower S. sanguinis viability in monospecies biofilm (P = 0.007). Metabolic activity was similar among all biofilms. In SEM both surfaces on C. albicans biofilm show a similar distribution of hyphae in mono and duospecies biofilms. AE surface has more S. sanguinis than the NanoHA surface in the duospecies biofilm. CLSM showed a large proportion of live cells in all groups.
CONCLUSIONS: The nanoHA surface reduced the adhesion of S. sanguinis biofilm but did not alter the adhesion of C. albicans or the biofilm formed by both species.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.