Physico-chemical behavior of magnesium-doped hydroxyapatite/chitosan composite layers in simulated physiological conditions.

Hybrid additive-subtractive manufacturing of surface-modified CF/PEEK porous implants with high-low temperature assistance.

Direct ink writing (DIW) followed by debinding and sintering processes offers unique advantages for fabricating biodegradable porous metallic scaffolds while avoiding several key issues associated with powder bed fusion additive manufacturing. Although DIW has been successfully applied to Mg, Fe, and their alloys, Zn-based scaffolds fabricated by DIW remain largely unexplored. Here, we fabricated, for the first time, porous Zn-based scaffolds with a Zn@ZnO core-shell structure using DIW printing combined with debinding and high-temperature oxidation. Their microstructure, degradation behavior, electrochemical response, evolution of mechanical properties, and in vitro biocompatibility were systematically evaluated. Furthermore, the sintering and corrosion mechanisms of the scaffolds were analyzed. High-temperature oxidation produced ZnO shells with thicknesses of 0.5-9.2 μm and induced the formation of needle- or flake-like ZnO, enabling stable bonding among Zn@ZnO spheres. Specimens prepared at oxidation temperatures between 500 °C and 650 °C exhibited similar yield strength and elastic modulus, while the compressive strength increased significantly with higher oxidation temperatures. Throughout the 28 days of in vitro biodegradation, the mechanical properties of the scaffolds remained within the range of cancellous bone, with mass losses between 2.8% and 7.4%. During the 7-day direct culture, all specimens exhibited good cytocompatibility, as indicated by cell viabilities above 75% and elevated alkaline phosphatase (ALP) activity. Overall, this study demonstrates the great potential of DIW-fabricated Zn@ZnO scaffolds for biodegradable bone-substituting biomaterials. STATEMENT OF SIGNIFICANCE: Direct ink writing (DIW) has emerged as a promising technique for fabricating porous biodegradable metallic scaffolds due to its low energy consumption and broad material compatibility. However, the application of DIW to biodegradable Zn-based bone implants remains largely unexplored. In this study, a fabrication strategy combining DIW with high-temperature oxidation is proposed to produce porous Zn-based scaffolds with a unique Zn@ZnO core-shell architecture. Controlled oxidation enables the formation of a multiscale hierarchical pore structure and allows effective regulation of degradation behavior, mechanical performance, and cytocompatibility. This work provides insights into the DIW processing of Zn-based biodegradable metals and highlights the potential of Zn@ZnO scaffolds for biofunctional bone substitute applications.

Pathological microenvironments linked to aging, trauma, malignancies, and metabolic disorders significantly hinder bone fractures and frequently result in fracture nonunion, posing substantial worldwide clinical difficulties. Widely prevalent therapies encounter difficulties in addressing diverse anatomical defects and variable illness conditions due to their inflexible designs and limitations in empirical optimization. Efficient strategies are critical to restore mechanics, improve pathological microenvironments, enhance neovascularization, and adapt to anatomical defects and clinical conditions. Deep learning networks (DLN) excel at analyzing extensive nonlinear relationships, enabling predictions of biomaterial‑biological interactions, hence accelerating biomaterial development. This study presents a synergistic DLN and 4D printing approach to fabricate a microenvironment-adaptive bioactive scaffold (MABS) for enhanced osteogenesis and angiogenesis. The scaffold integrates bioactive glass and a shape-memory PgP matrix, with a multilayer perceptron (MLP) neural network optimizing its design via nonlinear parameter-performance analysis. In vivo investigations revealed that the DLN-optimized scaffold enhanced shape-morphing adaptability and promoted the formation of dense bone tissue and vascular networks. This paradigm shift-employing DLN to integrate 4D printing dynamics, degradation kinetics, and multi-scale biological responses-transforms bone implants from static entities to dynamically adaptive systems, offering a scalable, intelligent framework for precise bone repair that rectifies the deficiencies of current strategies.

3D bone printing via ultrasound-mediated osteogenic differentiation of stem cells (3DBonUS).

Introduction and AimThe aim of this study was to compare the influence of zirconia dioxide nanoparticles (ZrO2‐NPs) and titanium dioxide nanoparticles (TiO2‐NPs) on the functionality of osteocytes in vitro.MethodsMLO‐Y4 osteocytic cells were treated with varying concentrations of ZrO2‐NPs or TiO2‐NPs for viability studies. Apoptosis assays following treatment with 100 and 500 µg/mL of ZrO2‐NPs or TiO2‐NPs for 72 h were performed. Sclerostin (SOST) levels were assessed at 24 and 72 h, while receptor activator of nuclear factor kappa‐B ligand (RANKL) and osteoprotegerin (OPG) were measured at 72 h by ELISA and real‐time PCR analysis.ResultsViability assays revealed a dose‐dependent cytotoxicity for both types of nanoparticles, with TiO2‐NPs reducing cell viability at 100 µg/mL within 24 h, while ZrO2‐NPs promoted proliferation at lower concentrations but showed similar cytotoxicity at higher doses. Apoptosis and necrosis assays revealed a dose‐dependent cytotoxic response, with TiO2‐NPs inducing significant cell death at 100 µg/mL, while ZrO2 NPs showed minimal effects at the same concentration; at 500 µg/mL, both nanoparticles markedly increased apoptosis, with TiO2‐NPs eliciting higher apoptosis. SOST gene expression and SOST release were significantly enhanced following exposure to both ZrO2‐NPs and TiO2‐NPs, with TiO2‐NPs inducing significantly higher levels. TiO2‐NPs upregulated RANKL while downregulating OPG both at the gene and protein levels. Although ZrO2‐NPs exhibited a similar trend, their impact on SOST expression, RANKL, and OPG release was notably lower, suggesting a potentially less disruptive impact on bone remodeling.ConclusionThe findings offer valuable insights into the osteocyte‐mediated effects of implant‐related nanoparticles. ZrO2‐NPs are a less disruptive alternative to TiO2‐NPs for bone implants, offering insights into osteocyte‐mediated remodeling and guiding biomaterial selection for implant longevity.

Rat caudal vertebrae are widely used in bone regeneration and spinal fusion research as convenient sites for testing bone graft materials and implants. Prior rat tail fusion models have achieved intervertebral fusion through disc removal and bone grafting, or with external fixation devices. Nonetheless, no such small-animal model has been developed that uses an interbody fusion cage analogous to that used clinically. It was hypothesized that an evaluable bone fusion environment could be established without neurological complications by performing a posterior cage insertion mimicking clinical procedures, supplemented with plate fixation, in the rat caudal vertebrae. This preliminary pilot study (n = 1) was designed to evaluate technical feasibility. A surgical approach was developed in which a miniaturized titanium cage was precisely inserted into the resected disc space between the adjacent caudal vertebrae, closely mirroring the human surgical procedure. Titanium was selected for the cage owing to its widespread clinical use and biocompatibility. The initial results demonstrated the technical feasibility of this approach. The implanted cage maintained disc height and spinal alignment. Progressive bone ingrowth through the cage was observed, culminating in confirmed continuous bone bridging across the intervertebral space by 12 weeks postoperatively. The presence of continuous trabecular structure and the absence of intervening fibrous tissue were confirmed radiologically and histologically. Overall, this cage-based rat tail fusion model provides a promising platform for evaluating novel biomaterials and investigating mechanisms of intervertebral bone fusion. However, the lack of a control group and statistical analysis, due to the single-subject design, limits the generalizability of these findings and necessitates further validation.

High-throughput synthesis of zinc-functionalized bio-ceramics propels the rational design of bone implants

Introduction: Primary implant stability is a critical factor in successful osseointegration. It is influenced by several variables such as bone density, implant design, and the surgical technique employed. The surgical technique plays a particularly crucial role in low-density bone. Aim: To evaluate the primary stability of implants placed using the proposed drilling technique, the osseodensification technique, and the standard drilling technique in low-density bone. Materials and Methods: This randomised clinical study was conducted in the Department of Implantology, Rajarajeswari Dental College and Hospital, Bengaluru Karnataka, India, from March 2022 to February 2023. A total of 57 participants (75 dental implants - 40 in maxilla and 35 in mandible) were enrolled and randomly assigned to one of the three drilling protocol groups, group I- Proposed drilling protocol (n=25 implants) were placed and group II- Osseodensification technique (n=25 implants) and group III- Standard drilling technique (n=25 implants). Insertion Torque (IT) and Implant Stability Quotient (ISQ) were measured as a measure of primary stability. Descriptive statistics were used to measure IT, Resonance Frequency Analysis (RFA) value in terms of mean and standard deviation for each group. One-way Analysis of Variance (ANOVA) test followed Tukey’s post-hoc test was used to compare the mean IT and RFA between the three groups. The level of significance was set at p-value <0.05. Results: This study included 57 patients, of whom 34 were females and 23 were males, with an age range of 20–62 years and a mean age of 41 years. The mean Insertion Torque (IT) value in group I was 46.75±4.94 Ncm, in group II was 43.25±3.73 Ncm, and in group III was 31.50±4.01 Ncm. Group I demonstrated a significantly higher mean IT compared to group II (p=0.03) and group III (p<0.001). Additionally, group II showed a significantly higher mean IT compared to group III (p<0.001). The mean Implant Stability Quotient (ISQ) in group I was 65.90±3.74, in group II was 60.83±3.29, and in group III was 56.78±3.25. Group I demonstrated a significantly higher mean ISQ compared to both group II and group III (p<0.001). Conclusion: Primary stability of implants placed in lowdensity bone was enhanced with the proposed drilling and osseodensification techniques when compared to the conventional drilling technique.

Fatigue performance of additively manufactured porous titanium for orthopaedic applications.

4D scaffolds offer transformative potential for bone implants. Yet their application to metallic materials is constrained by the scarcity of suitable alloys and the requirement for harsh external stimuli to trigger shape change. Here, we introduce 4D metallic metamaterials driven by controlled biodegradation that combine biodegradable constraints with biometals of higher corrosion potential. We show that upon electrochemical degradation of the constraint, the metamaterials recover their original geometry-via stretching, bending, or expansion-generating programmable recovery forces tuned through structural design parameters. We demonstrate that when turned into scaffolds for bone implants, the 4D metallic metamaterials are cytocompatible and promote bone regeneration through the synergistic effects of bioactivity and mechanical stimulation in vivo. This strategy establishes a paradigm in 4D shape transformation of metal via metamaterial design, enabling bioactive, self-recovering implants with broad applicability across biomedical engineering.

Chondroblastoma of the capital femoral epiphysis (CHCFE) in children is a rare benign bone tumor that poses significant therapeutic challenges due to its unique anatomic location adjacent to the physeal plate and femoral head articular cartilage. This study aimed to evaluate the clinical efficacy and safety of a cartilage fenestration approach combined with artificial bone implantation for the treatment of CHCFE. A retrospective analysis was conducted on 25 consecutive pediatric patients (14 boys and 11 girls; mean age, 10.5y; range, 6 to 14y) diagnosed with CHCFE and treated at our institution between January 2011 and October 2021. All patients underwent cartilage fenestration plus curettage and artificial bone (calcium sulfurphosphorus composite) implantation. Lesions were classified into 4 types based on anatomic involvement: medial (n=8), central (n=10), lateral (n=5), and medial-central (n=2). The mean follow-up duration was 67.5 months (range, 24 to 145mo). Clinical outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) functional score, with recurrence, complications [eg, avascular necrosis (AVN), physeal premature closure], and radiologic findings recorded. All patients had open epiphyseal plates preoperatively. The mean MSTS score improved significantly from 18.56 preoperatively to 27.40 postoperatively (P<0.001). At final follow-up, only 1 case (4%) of tumor recurrence was observed, and no AVN of the femoral head was detected. Among 16 patients with preoperative physeal plate invasion, 7 (43.75%) developed mild-to-moderate proximal femoral epiphyseal premature closure, predominantly in the lateral lesion group. Multivariate analysis identified preoperative femoral head involvement location as the only independent factor affecting postoperative MSTS scores (P=0.026), with lateral involvement associated with the lowest functional scores (mean, 23.00) compared with medial (27.88), central (28.10), and medial-central (27.00) involvement. The cartilage fenestration approach combined with artificial bone implantation is a safe and effective minimally invasive treatment for CHCFE in children, offering thorough tumor clearance, significant functional improvement, and low rates of recurrence and AVN. However, lateral involvement of the femoral head indicates a relatively poor prognosis, requiring more meticulous surgical planning and postoperative rehabilitation to optimize outcomes. Level IV-case series.

In situ engineered silicon-magnesium implants orchestrate sequential immunomodulation, angiogenesis, and osteogenesis for bone repair

The adoption of biodegradable synthetic polymers in biomedical and tissue engineering becomes a focal point, offering alternative solutions to organ transplantation and conventional permanent restoration. The key principle in developing scaffold-based for physiological implantation is the synchronisation of polymer’s degradation kinetics with the regeneration timeline of host tissues. Different implantation lesions exhibit vastly different healing durations, ranging from a few weeks to several months or years. A mismatch timeline can be detrimental where premature degradation will remove the physical framework needed for cell integration, whereas overly slow degradation will restrict spaces for new tissue growth. This review study provides a comprehensive discussion on the degradation mechanisms of biodegradable synthetic polymers in physiological environments. Four widely studied polymers—polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), and polyurethane (PU)—were reviewed in depth on the degradation mechanisms and influencing factors. Scientific experimental data from the previous studies were summarised, including degradation percentage, experimental conditions, degradation timeline, and estimated complete degradation period. Specifically, four degradation mechanisms are associated with the degradation of synthetic polymers in physiological environments including chemical hydrolysis, enzymatic-mediated metabolism, oxidative degradation, and pH-dependent degradation. Each of the mechanisms may act independently or synergistically under different biological conditions. The degradation of polymers is accordingly influenced by the chemical structures, fabrication routes, degradation pathways, and physicochemical factors. These data are correlated with their optimal use in biomedical and TE applications for fast regenerating tissues to slow-healing or load-bearing structures. Comprehensively, PVA is aligned well with short-to-intermediate healing tissues such as the skin and the cornea due to its high degradation capability, while PLA, PCL, and PU that degrade from weeks to years are suitable for mediate-healing soft tissues to long-term implantations such as load-bearing bone, cartilage, ligament, neural, and vascular implantations. By aligning polymer degradation profiles with the biological timelines of tissue regeneration, this review provides a translational framework for synthetic polymer selection to enable optimum scaffold’s functionalities and clinical outcomes.

Osteoclasts and foreign body giant cells (FBGCs) are multinucleated cells derived from monocytes, but they have distinct functions. Osteoclasts resorb bone while FBGCs form in response to foreign material. Regarding bone implants, osteoclasts are responsible for implant integration, but also for bone resorption associated to implant loosening, while FBGCs play a role in the immune response to the foreign material. Little is known about which proteins in the local environment fine-tune the multinucleation of osteoclasts or FBGCs. One candidate is Activin A (ActA). It has been shown to induce larger, more active osteoclasts, but its effect on FBGC differentiation is unknown. We investigated the effect of ActA on the differentiation of osteoclasts and FBGCs from human CD14-positive monocytes. The number of multinucleated cells and the cell area was measured. qPCR was performed to assess the effect of ActA on gene expression. ActA's influence on osteoclast and FBGC formation was studied on plastic, bone and hydroxyapatite coated Titanium discs (ALD-HA). ActA induced fewer, but bigger and more active osteoclasts on plastic and bone. In contrast, ActA did not have an effect on FBGC number. On ALD-HA, ActA reduced the number of FBGCs, but did not influence osteoclast numbers. qPCR showed that ActA upregulated the expression of several genes such as TRAcP, CIITA, OLR1, RHOBTB1 and ALK4, but mainly in osteoclasts. These results show that ActA has a different effect on osteoclasts compared to FBGCs. This difference could be caused by a difference in the expression in the canonical ActA receptor ALK4.

Advanced gentamicin-loaded chitosan/hydroxyapatite/mesoporous SiO2 scaffold: A comprehensive investigation of drug delivery and cellular interactions.

Finite element analysis (FEA) is a technique for obtaining a solution to a complex mechanical problem by dividing the problem domain into a collection of much smaller and simpler domains (elements) in which the field variables can be interpolated with the use of shape functions. Load transfer from implants to surrounding bone depends on the type of loading, the bone-implant interface, the length and diameter of the implants, the shape and characteristics of the implant surface, the prosthesis type and the quantity and quality of the surrounding bone. FEA allows researchers to predict stress distribution in the contact area of the implants with the cortical bone and around the apex of the implants in trabecular bone. This study aimed to compare the stress and strain on a single implant and its surrounding bone for various implant lengths and diameters, both before and after osseointegration. An initial model of a single implant substituting a second premolar was developed with reference to a posterior cross-sectional area of both cortical and cancellous bone on a personal computer using ANSYS software. The length and diameter of the implant were assumed to be L = 11.5 mm and D = 4 mm. The loading condition was performed by the application of the static vertical force of 118.2 N to the node of the implant. Increased implant length results in stress reduction on the implant in both immediate and delayed implant loading. In the present study, the Von Miss Stress are reduced. Furthermore, increased implant diameter results in stress reduction on the implant in both immediate and delayed implant loading. The present study indicates that implant length prior to and after osseointegration is not the sole factor affecting stress/strain distribution pattern. There are other influencing factors like type of loading, the bone-implant interface, the length and diameter of the implants, the shape and characteristics of the implant surface, the prosthesis type and the quantity and quality of the surrounding bone.

Pro-osteogenic implants inhibit local excessive B cell maturation via neutrophils-derived CD52 signaling to enhance osseointegration.

Background and objectivePercutaneous screw fixation (PSF) technique is widely used in treating displaced intra-articular calcaneal fractures (DIACFs), the optimal screw configuration remains controversial. In this study, a finite element analysis (FEA) was conducted to compare the biomechanical properties of five different screw configurations in the fixation of Sanders type ⅡB calcaneal fractures, aiming to provide a reference for clinical strategy selection.MethodsIn this study, models of five different screw configurations for the fixation of Sanders type IIB calcaneal fractures were constructed. After assigning material properties and applying stress, the maximum displacement and von Mises stress distribution of bone fragments and implants in each group were recorded and compared through FEA.ResultsAfter loading, the maximum displacement and von Mises stress of the bone fragments in the five models were recorded as follows: Model 1 (0.369 mm, 39.803 MPa), Model 2 (0.335 mm, 42.283 MPa), Model 3 (0.297 mm, 39.079 MPa), Model 4 (0.315 mm, 33.770 MPa), and Model 5 (0.415 mm, 41.095 MPa). The maximum displacement and stress of the screws were recorded as: Model 1 (0.286 mm, 34.439 MPa), Model 2 (0.277 mm, 35.489 MPa), Model 3 (0.233 mm, 60.152 MPa), Model 4 (0.247 mm, 38.725 MPa), and Model 5 (0.330 mm, 46.806 MPa), Model 3 exhibiting the best mechanical performance, while Model 5 showed the least favorable performance.ConclusionsFEA results demonstrate that the use of multiple sustentaculum tali screws and a “kickstand” screw to enhance fixation of the posterior articular surface, along with longitudinal screws inserted superior to the Achilles tendon insertion contributed to stability. The longitudinal screws inserted from the calcaneal tuberosity provide relatively poor stability. Additionally, reinforcing the fixation of the medial column of the calcaneus enhances stability.

The manuscript details the influence of high-temperature and high-shear processing, as well as radiation sterilization, on properties of bioresorbable and osteoconductive, patient-tailored alloplastic scaffolds for guided bone regeneration. Functionalized poly(l-lactide-co-d,l-lactide) copolymer filled with hydroxyapatite was used to produce two personalized implants for upper and lower jaw reconstruction via 3D printing. Morphology analysis (SEM, µCT), gel permeation chromatography, and thermal analysis quantified the effects of melt processing and sterilization on chain structure. Physical properties of sterilized parts, such as hardness and density, proved suitable for bone implants. Removal of the upper jaw implant after 4 months and of the lower jaw substitute after 18 months enabled monitoring of bioresorption and tissue regrowth over time. Gradual overgrowth of the implants with human tissue, initiated by the osteoconductive filler, was observed, along with time-dependent polylactide degradation, showing up to 92% molar mass reduction. The medical procedures confirmed safety, nontoxicity, non-allergenicity, and, most importantly, the tissue-forming properties of the polylactide-based formulation.