Complex Bone Defects Research Articles

Cisplatin-functionalized dual-functional bone substitute granules for bone defect treatment after bone tumor resection

Invasive bone tumors pose a significant healthcare challenge, often requiring systemic chemotherapy and limb salvage surgery. However, these strategies are hampered by severe side effects, complex post-resection bone defects, and high local recurrence rates. To address this, we developed dual-functional bone substitute biomaterials by functionalizing commercially available bone substitute granules (Bio-Oss® and MBCP®+) with the established anticancer agent cisplatin. Physicochemical characterization revealed that Bio-Oss® granules possess a higher surface area and lower crystallinity compared to MBCP®+ granules, which enhances their capacity for cisplatin adsorption and release. In co-cultures with metastatic breast and prostate cancer cells (MDA-MB-231 and PC3) and bone marrow stromal cells (hBMSCs), cisplatin-functionalized granules and their releasates exhibited dose-dependent cytotoxic effects on cancer cells while having less impact on hBMSCs. Furthermore, investigations on the mechanism of action indicated that cisplatin induced significant cell cycle arrest and apoptosis in MDA-MB-231 and PC3 cells, contrasting with minimal effects on hBMSCs. In a rat femoral condyle defect model, cisplatin-functionalized granules did not evoke adverse effects on bone tissue ingrowth or new bone formation. Importantly, local application of cisplatin-functionalized granules resulted in negligible cisplatin accumulation without signs of apoptotic damage in kidneys and livers. Taken together, we here provide hard evidence that cisplatin-functionalized granules maintain a favorable balance between biosafety, anticancer efficacy, and bone regenerative capacity. Consequently, loading granular bone substitutes with cisplatin holds promise for local treatment of bone defects following bone tumor resections, presenting a safe and potentially more effective alternative to systemic cisplatin administration. Statement of SignificanceCurrent treatments in combating malignant bone tumors are hampered by severe side effects, high local tumor recurrence, and complex bone defects after surgery. This study explores a facile manufacturing method to render two types of commercially available bone substitute granules (Bio-Oss® and MBCP®+) suitable for local delivery of cisplatin. The use of cisplatin-functionalized granules has shown promising results both in killing cancer cells in a dose-dependent manner and in aiding bone regeneration. Importantly, this local treatment strategy avoids the systemic toxicity associated with traditional chemotherapy to excretory organs. This dual-functional strategy represents a significant advancement in bone cancer treatment, offering a safe and more efficient alternative that could improve outcomes for patients following bone tumor resection.

Innovative approaches to cage reconstructions in orthopedic limb surgery: Advances and insights with two cases

BackgroundLimb tumors, though rare, pose significant challenges to surgical management due to their impact on limb function and quality of life. Effective treatment requires precise tumor resection alongside advanced reconstructive techniques to restore limb function, particularly in cases of compromised bone healing. Titanium cages, traditionally used in spinal surgeries, have recently gained attention for their potential in limb reconstruction within orthopedic oncology, offering a novel approach to managing complex bone defects. Case PresentationThis retrospective case series presents two patients treated with titanium cages for limb reconstruction following tumor resection.Case 1: A 53-year-old female with a solitary plasmacytoma of the femur experienced a pathological fracture and nonunion after initial treatment. A titanium cage was employed to bridge the resected bone segment, leading to successful callus formation at the six-month follow-up and restored limb function.Case 2: A 31-year-old female with a giant cell tumor and hemangioma of the foot underwent en bloc resection followed by reconstruction using a vertebral cage and iliac corticospongious graft. Six months postoperatively, the patient had resumed full weight-bearing with no complications. ConclusionTitanium cages offer a promising solution for limb reconstruction in patients with tumors, particularly for large bone defects where traditional methods may be inadequate. This case series demonstrates successful outcomes in limb preservation and functional recovery using titanium cages. Their use in the adult population shows potential for broader application in orthopedic oncology, warranting further clinical investigation.

Shape Memory Polymer Bioglass Composite Scaffolds Designed to Heal Complex Bone Defects.

An off-the-shelf scaffold with requisite properties could enable the viable treatment of irregular craniomaxillofacial bone defects. Notably, the scaffold should be conformally fitting, innately bioactive, and bioresorbable. In prior work, we developed a series of shape memory polymer (SMP) scaffolds based on cross-linked poly(ε-caprolactone) (PCL). These were capable of "self-fitting" into complex bone defects when exposed to temperatures above the melt transition of the constituent PCL, either linear-PCL-diacrylate (linear-PCL-DA, Tm ∼55 °C) or star-PCL-tetraacrylate (star-PCL-TA, Tm ∼45 °C) for the potential to improve tissue safety. To achieve favorably increased degradation rates versus PCL-only scaffolds, semi-interpenetrating networks (semi-IPNs) were formed by including linear- or star-poly(l-lactic acid) (PLLA). A potential limitation of these self-fitting scaffolds is the lack of bioactivity, which is essential to osteoinductivity and osseointegration. Herein, analogous composite scaffolds were formed with 45S5 bioglass (BG) to impart bioactivity. The solvent-cast particulate leaching fabrication method was adapted to introduce BG to the fused salt template, resulting in composites with BG concentrated on the pore wall surfaces rather than within pore struts. Composite scaffolds with good pore wall integrity were produced with 2.5, 5, and 10 wt % BG. All composite scaffolds exhibited non-brittle behavior and did not fracture with 85% strain. For semi-IPN composite scaffolds, PLLA crystallinity was lost, and mechanical properties were not appreciably altered versus the non-BG controls. Sufficient retention of PCL crystallinity led to excellent shape memory behavior. The inclusion of 5 and 10 wt % BG led to hydroxyapatite mineralization after 1 day of exposure to simulated body fluid, as well as increased rates of in vitro degradation.

3D chitosan scaffolds loaded with ZnO nanoparticles for bone tissue engineering

Bone defect has always been a difficult problem in clinical work. According to the current research results, tissue engineered scaffolds with a single function, structure, and composition are not sufficient to repair complex bone defects. In this work, a three-dimensional (3D) chitosan degradable composite scaffold loaded with zinc oxide (ZnO) was constructed, and the effect of ZnO content on scaffold performance and osteogenesis was explored. The 3D composite scaffold was prepared by freeze-drying technology. The microstructure, porosity, degradation performance, release performance, swelling performance, cytotoxicity, cell adhesion and osteogenic ability of ZnO nanoparticles and chitosan (ZnONPs/CS) composite scaffolds were measured. The results show that an appropriate amount of ZnO may be helpful to regulate the stability and degradation characteristics of the scaffold to a certain extent. Moreover, the composite scaffold could release ZnO into the simulated body fluid environment. The appropriate amount of ZnO helps to promote the proliferation, adhesion, and osteogenic differentiation of MC3T3-E1 cells. At a ZnO content of 3wt%, both in vitro and vivo results showed relatively optimal biocompatibility and bioactivity of the scaffolds. This work could at least provide some positive insights for the selection of ZnO dosage, construction of chitosan-based 3D scaffolds, tissue engineering applications, and clinical treatment.

ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.

Fabrication Strategies for Bioceramic Scaffolds in Bone Tissue Engineering with Generative Design Applications.

The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic-polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering.

Microbiological challenges in the treatment of war injuries

The treatment of war injuries represents a continuing and recurrent challenge in modern reconstructive surgery. Previously, tumor resections and sepsis-related resections were mainly responsible for lengthy bone defects in Germany. In recent years another picture has increasingly emerged, particularly caused by the medical support of Ukraine. Aspects of military surgery are also becoming more important in civil hospitals, especially in the treatment of gunshot and explosion injuries. In Germany, war injuries are currently secondarily treated, as the distribution of patients is carried out according to the cloverleaf principle, weeks or months after the occurrence of the primary injury. In addition to complex bone and soft tissue defects of the extremities following such injuries, which often affect neural and vascular structures, reconstruction is often complicated by an increasing spectrum of multidrug-resistant pathogens. The definition of microbiological terms, such as contamination, colonization, critical colonization, local and systemic infections are important in the clinical routine in order to initiate a targeted treatment, especially in treatment with antibiotics. Wound swabs for determination of the spectrum of pathogens and the optimal testing of resistance are important for selecting the appropriate antibiotic agents. The concept of antibiotic stewardship (ABS) is established in many hospitals to improve the quality of antibiotic treatment and to minimize the formation of resistance. The selection of the method of reconstruction depends on the condition of the patient, the overall clinical constellation and the function to be expected after completion of treatment. The treatment of injuries due to violence and terrorism necessitates clear concepts and an interdisciplinary approach, especially with respect to microbiological challenges and increasing resistance situations.

Integration of BMP-2/PLGA microspheres with the 3D printed PLGA/CaSO4 scaffold enhances bone regeneration

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.

Treatment of open fracture bone defect of distal femur with antibiotic cement column and bone graft

To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treatment of open fracture with bone defect of distal femur. From October 2014 to March 2021, 16 patients of open fracture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft, including 12 males and 4 females. The age ranged from 28 to 68 years old. There were 11 cases of traffic accident injury, 5 cases of falling injury, 3 cases as Gustilo type Ⅰ, 5 cases as type Ⅱ and 8 cases as type ⅢA. AO classification was used:9 cases of C2 type and 7 cases of C3 type. The time from injury to final bone grafting ranged from 4 to 119 days. The length of bone defect ranged from 2 to10 cm. Fractures healing time, complications and knee function Merchan score were recorded. All the 16 patients were followed up from 9 to 29 months. The incisions of 16 patients healed in one stage without postoperative infection, plate fracture, limb shortening and valgus and varus deformity. The healing time randed from 4 to 10 months . Knee joint function according to the Merchant scoring standard, showed that 8 cases were excellent, 4 cases were good, 3 cases were fair, and 1 case was poor. The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection, assist fracture reduction, increase fixation strength and significantly reduce the amount of bone grafting.

Matrix Metalloproteinase-Responsive Hydrogel with On-Demand Release of Phosphatidylserine Promotes Bone Regeneration Through Immunomodulation.

Inflammation-responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)-responsive injectable hydrogel is constructed by integrating an MMP-cleavable peptide (pp) into a covalent tetra-armed poly-(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro-regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG-pp-PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG-pp-PS to transform macrophages into the anti-inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell-free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Suitability of Gelatin Methacrylate and Hydroxyapatite Hydrogels for 3D-Bioprinted Bone Tissue.

Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects; however, its limitations include donor-site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. In this experiment, gels composed of varying levels of gelatin methacrylate (GelMA) and hydroxyapatite (HA) and gelatin concentrations are explored. The objective was to increase the hydroxyapatite content and find the upper limit before the printability was compromised and determine its effect on the mechanical properties and cell viability. Design of Experiments (DoE) was used to design 13 hydrogel bioinks of various GelMA/HA concentrations. These bioinks were assessed in terms of their pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Three bioinks, one with the DoE-designed maximal stiffness, one with the experimentally defined maximal stiffness, and a literature-based control, were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. The DoE ANOVA analysis indicated that the augmented three-level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% gelatin. There were no significant differences in the cell viability within the hydrogels from day 2 to day 7 (p > 0.05). There was, however, a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with a lower HA concentration (p < 0.05), showing that a higher HA content or print pressure may be cytotoxic within hydrogels. Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates that it is possible to create printable bone-like grafts from GelMA and HA with an increased HA content, favorable mechanical properties (145 kPa), and a greater than 80% cell viability.

A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration

BackgroundCoordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities.ResultsHerein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-β (TGF-β) signaling pathway.ConclusionOverall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.Graphical

Guided Customization and Fixation of Allogenic Cortical Lamina in Alveolar Bone Regeneration. A Case Report.

Bone reconstruction surgeries such as the autogenous and allogenic shell techniques where cortical laminates are used to regenerate bone defects, requires time and expertise to adapt and fix the laminated cortical blocks onto the defect area. This case report illustrates the process of customizing and fixing an allogenic cortical laminate (ACL) to reconstruct a horizontal bone defect with guided surgical stents. Two types of surgical stents were designed: one to aid in cutting a prefabricated ACL into the desired shape for the defect to be regenerated, and the other type of stent, was used to assist in the positioning and fixation of the resulting laminates. These stents enabled the clinician to regenerate a horizontal defect with reduced surgical time, increased precision and safety during laminate fixation. After 5 months of healing a dental implant could be placed in the regenerated site. The use of surgical stents in this type of bone regeneration surgeries can be helpful specially in more complex bone defects where precision is key. Further clinical studies are needed to validate this technique.

Research progresses on mitochondrial-targeted biomaterials for bone defect repair.

In recent years, the regulation of the cell microenvironment has opened up new avenues for bone defect repair. Researchers have developed novel biomaterials to influence the behavior of osteoblasts and immune cells by regulating the microenvironment, aiming to achieve efficient bone repair. Mitochondria, as crucial organelles involved in energy conversion, biosynthesis and signal transduction, play a vital role in maintaining bone integrity. Dysfunction of mitochondria can have detrimental effects on the transformation of the immune microenvironment and the differentiation of stem cells, thereby hindering bone tissue regeneration. Consequently, targeted therapy strategies focusing on mitochondria have emerged. This approach offers a wide range of applications and reliable therapeutic effects, thereby providing a new treatment option for complex and refractory bone defect diseases. In recent studies, more biomaterials have been used to restore mitochondrial function and promote positive cell differentiation. The main directions are mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial quality control. In this review, we investigated the biomaterials used for mitochondria-targeted treatment of bone defect repair in recent years from the perspective of progress and strategies. We also summarized the micro-molecular mechanisms affected by them. Through discussions on energy metabolism, oxidative stress regulation and autophagy regulation, we emphasized the opportunities and challenges faced by mitochondria-targeted biomaterials, providing vital clues for developing a new generation of bone repair materials.

Injectable in situ gelling methylcellulose-based hydrogels for bone tissue regeneration.

Injectable bone substitutes (IBSs) represent a compelling choice for bone tissue regeneration, as they can be exploited to optimally fill complex bone defects in a minimally invasive manner. In this context, in situ gelling methylcellulose (MC) hydrogels may be engineered to be free-flowing injectable solutions at room temperature and gels upon exposure to body temperature. Moreover, incorporating a suitable inorganic phase can further enhance the mechanical properties of MC hydrogels and promote mineralization, thus assisting early cell adhesion to the hydrogel and effectively guiding bone tissue regeneration. In this work, thermo-responsive IBSs were designed selecting MC as the organic matrix and calcium phosphate (CaP) or CaP modified with graphene oxide (CaPGO) as the inorganic component. The resulting biocomposites displayed a transition temperature around body temperature, preserved injectability even after loading with the inorganic components, and exhibited adequate retention on an ex vivo calf femoral bone defect model. The addition of CaP and CaPGO promoted the in vitro mineralization process already 14 days after immersion in simulated body fluid. Interestingly, combined X-ray diffraction and solid state nuclear magnetic resonance characterizations revealed that the formed biomimetic phase was constituted by crystalline hydroxyapatite and amorphous calcium phosphate. In vitro biological characterization revealed the beneficial impact of CaP and CaPGO, indicating their potential in promoting cell adhesion, proliferation and osteogenic differentiation. Remarkably, the addition of GO, which is very attractive for its bioactive properties, did not negatively affect the injectability of the hydrogel nor the mineralization process, but had a positive impact on cell growth and osteogenic differentiation on both pre-differentiated and undifferentiated cells. Overall, the proposed formulations represent potential candidates for use as IBSs for application in bone regeneration both under physiological and pathological conditions.

Advances in the Application of Bone Transport Techniques in the Treatment of Bone Nonunion and Bone Defects.

Bone nonunion and bone defects frequently occur following high-energy open injuries or debridement surgeries, presenting complex challenges to treatment and significantly affecting patients' quality of life. At present, there are three primary treatment options available for addressing bone nonunion and bone defects: vascularized bone grafts, the Masquelet technique, and the Ilizarov technique. The Ilizarov technique, also known as distraction osteogenesis, is widely favored by orthopedic surgeons because of several advantages, including minimal soft tissue requirements, low infection risk, and short consolidation time. However, in recent years, the application of the Masquelet technique has resulted in novel treatment methods for managing post-traumatic bone infections when bone defects are present. Although these new techniques do not constitute a panacea, they continue to be the most commonly employed options for treating complex large bone nonunion and bone defects. This review evaluates the currently available research on the Ilizarov and Masquelet bone transport techniques applied at various anatomical sites. Additionally, it explores treatment durations and associated complications to establish a theoretical foundation that can guide clinical treatment decisions and surgical procedures for the management of bone nonunion and bone defects.

Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds.

Current treatments for craniomaxillofacial (CMF) defects motivate the design of instructive biomaterials that can promote osteogenic healing of complex bone defects. We report methods to promote in vitro osteogenesis of human mesenchymal stem cells (hMSCs) within a model mineralized collagen scaffold via the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization. An addition of 5 w/v% ascorbic acid into the base mineralized collagen scaffold significantly changes key morphology characteristics including porosity, macrostructure, and microstructure. This modification promotes hMSC metabolic activity, ALP activity, and hMSC-mediated deposition of calcium and phosphorous. Additionally, the incorporation of ascorbic acid influences osteogenic gene expression (BMP-2, RUNX2, COL1A2) and delays the expression of genes associated with osteoclast activity and bone resorption (OPN, CTSK), though it reduces the secretion of OPG. Together, these findings highlight ascorbic acid as a relevant component for mineralized collagen scaffold design to promote osteogenic differentiation and new bone formation for improved CMF outcomes.

Ion incorporation into bone grafting materials.

The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.

Customized partial pelvis replacement: three-dimensional planning and management concepts

The planning and implantation of acustomized partial pelvis replacement places high demands on both the surgeon and the entire team (engineer, assistants, surgical team). Thanks to careful preoperative planning and meticulous perioperative execution, customized partial pelvic replacement represents a complex but reliable procedure for defect reconstruction even with highly complex acetabular bone defects or after multiple previous surgeries.

Cortical Mandibular Bone Blocks Grafts and Piezoelectric Surgery in Complex Anterior Maxillary Alveolar Defects: A Case Report and Literature Review

The aim of this study is to assess the indication and efficacy of alveolar ridge reconstructions for complex horizontal and vertical augmentation procedures in the maxillary anterior area with Cortical Mandibular Bone Block Grafts (CMBBG). Localized alveolar three-dimensional bone defects are among the most challenging problems in surgical implant dentistry. Treatment protocols, such as short implants or small diameter implants are not always offering the desired clinical and esthetic results. The autogenous augmentation procedure can serve as an option, which allows a more biological reconstruction of the vertical and horizontal dimension of a complex bone defect in order to obtain sound replicas of natural teeth. The clinical case of a cortical autogenous block graft in an anterior complex maxillary defect is presented along with a literature review. The presented case and the selected articles demonstrate that cortical ramus bone block grafts show relatively low graft resorption, low donor site morbidity and high implant success rates.