Osteoinductive Materials Research Articles

Osteoinductive biomaterials: Machine learning for prediction and interpretation

Biomaterials with osteoinductivity are widely used for bone defect repair due to their unique structures and functions. Machine learning (ML) is pivotal in analyzing osteoinductivity and accelerating new material design. However, challenges include creating a comprehensive database of osteoinductive materials and dealing with low-quality, disparate data. As a standard for evaluating the osteoinductivity of biomaterials, ectopic ossification has been used. This paper compiles research findings from the past thirty years, resulting in a robust database validated by experts. To tackle issues of limited data samples, missing data, and high-dimensional sparsity, a data enhancement strategy is developed. This approach achieved an area under the curve (AUC) of 0.921, a precision of 0.839, and a recall of 0.833. Model interpretation identified key factors such as porosity, bone morphogenetic protein-2 (BMP-2), and hydroxyapatite (HA) proportion as crucial determinants of outcomes. Optimizing pore structure and material composition through partial dependence plot (PDP) analysis led to a new bone area ratio of 14.7 ± 7 % in animal experiments, surpassing the database average of 10.97 %. This highlights the significant potential of ML in the development and design of osteoinductive materials. Statement of significanceThis study leverages machine learning to analyze osteoinductive biomaterials, addressing challenges in database creation and data quality. Our data enhancement strategy significantly improved model performance. By optimizing pore structure and material composition, we increased new bone formation rates, showcasing the vast potential of machine learning in biomaterial design.

Osteoinductive Properties of Autologous Dentin: An Ex Vivo Study on Extracted Teeth.

Over the last decades, a variety of biomaterials, ranging from synthetic products to autologous and heterologous grafts, have been recommended to conserve and regenerate bone tissue after tooth extraction. We conducted a biochemical study on ground extracted teeth that aimed to evaluate the osteoinductive and osteoconductive potential of dentin by assessing the releases of bone morphogenetic protein (BMP-2), osteocalcin (OC) and osteonectin (ON) over time (24 h, 10 days and 28 days). Twenty-six patients, who required the extraction of nonrestorable teeth, were enrolled in the study according to the inclusion criteria, as follows: thirteen young patients 18 to 49 years of age (UNDER 50), and thirteen patients of 50 to 70 years (OVER 50); a total of twenty-six teeth were extracted, ground and analyzed by enzyme-linked immunosorbent assays (ELISA). All ground teeth released BMP-2, OC and ON at each time point; no differences were observed between the UNDER-50 and OVER-50 patients. The results of the study support the use of autologous dentin as osteoinductive material for bone regeneration procedures, irrespective of patients' ages.

A novel Mg-Zn-Nd-Zr alloy lumbar interbody fusion cage: An in vitro and in vivo study

Interbody fusion is recognized as the golden standard of surgical intervention for degenerative disc disease (DDD). Interbody fusion cage made of polyetheretherketone (PEEK) is commonly used in lumbar interbody fusion surgery in the treatment of DDD worldwide. However, there are some limitations of PEEK including their bio-inert nature and impediment to host bone integration. This study aimed to evaluate the degradation profile and osteoinductive potential of biodegradable Mg-Zn-Nd-Zr cages with/without micro-arc oxidation (MAO) coatings. The Mg-Zn-Nd-Zr alloy cages, whether coated with MAO or not, demonstrated commendable biocompatibility and biomechanical properties. Immersion and electrochemical tests show better corrosion resistance of MAO coatings in vitro. mRNA sequencing, RT-qPCR and Western blotting revealed that Mg-Zn-Nd-Zr and Mg-Zn-Nd-Zr/MAO had a better effectiveness on osteoinductivity. In vivo evaluations in ovine models over 12 weeks and 24 weeks post-implantation revealed radiological and histological evidence of enhanced bone formation adjacent to the Mg-Zn-Nd-Zr alloy cages compared to PEEK counterparts. Moreover, the MAO-coated cages exhibited a reduced propensity for gas formation. The Mg-Zn-Nd-Zr alloy is as a superior osteoinductive material compared with PEEK, with the MAO coating offering an advantage in mitigating gas production. Nonetheless, further research is warranted to refine the alloy's composition or surface treatments, particularly to address the challenges associated with rapid gas evolution during the early post-implantation period.

Evaluation of β-tricalcium Phosphate (β-TCP) and Platelet Rich Plasma (PRP) Combination for Fracture Healing in Dogs Stabilized with Intramedullary Pinning

Background: The use of synthetic bone substitute,b-tricalcium phosphate (β-TCP) as an osteo-conductive material and platelet-rich plasma (PRP) as an osteo-inductive material is the alternate strategies for replenishing bone loss. Thus, the present study was conducted to evaluate the bone healing efficacy of β-TCP and PRP combination in dogs with long bone fracture repaired with threaded intramedullary pinning. Methods: Fifteen dogs were selected, which were allotted to two groups irrespective of age, breed and sex. In six dogs of Group I intramedullary pinning was performed, while in nine dogs of Group II β-TCP and PRP was applied at fracture site after stabilising with intramedullary pin. Clinical and radiographic examinations were conducted preoperatively and postoperatively on 15th, 30th and 60th day. Result: The mean weight bearing and radiographic union scores were better in group II animals as compared to group I at different time intervals. The present findings suggest that β-TCP and PRP effectively enhances the bone healing in dogs with long bone fracture.

The genetic background determines material-induced bone formation through the macrophage-osteoclast axis

Osteoinductive materials are characterized by their ability to induce bone formation in ectopic sites. Thus, osteoinductive materials hold promising potential for repairing bone defects. However, the mechanism of material-induced bone formation remains unknown, which limits the design of highly potent osteoinductive materials. Here, we demonstrated a genetic background link among macrophage polarization, osteoclastogenesis and material-induced bone formation. The intramuscular implantation of an osteoinductive material in FVB/NCrl (FVB) mice resulted in more M2 macrophages at week 1, more osteoclasts at week 2 and increased bone formation after week 4 compared with the results obtained in C57BL/6JOlaHsd (C57) mice. Similarly, in vitro, with a greater potential to form M2 macrophages, monocytes derived from FVB mice formed more osteoclasts than those derived from C57 mice. A transcriptomic analysis identified Csf1, Cxcr4 and Tgfbr2 as the main genes controlling macrophage-osteoclast coupling, which were further confirmed by related inhibitors. With such coupling, macrophage polarization and osteoclast formation of monocytes in vitro successfully predicted in vivo bone formation in four other mouse strains. Considering material-induced bone formation as an example of acquired heterotopic bone formation, the current findings shed a light on precision medicine for both bone regeneration and the treatment of pathological heterotopic bone formation.

Biodegradable biomaterials in orthopedic surgery: A narrative review of the current evidence.

Biomaterials are routinely used in orthopedic surgery to fill bone defects, improve bone healing, and as degradable fixation material. A wide range of materials are currently in use, and the materials are chosen according to their bioactive properties. Osteoinductive materials stimulate bone healing by promoting osteogenesis. Osteoconductive materials facilitate bone growth on the surface of the material. Despite the many materials in use and an increasing number of published studies, randomized controlled trials on the subject are scarce. This review aims to summarize the history of biodegradable biomaterials and also the published level I evidence currently available on orthopedic biomaterials. Most of the studies have been superiority trials with non-significant differences compared to conventional treatment options, confirming that several biomaterials are suitable treatment options for multiple indications including bone and/or tendon fixation, filling bone defects, and spinal fusion. Biomaterials help to avoid donor site complications associated with autogenous bone grafts and often eliminate the need for implant removal. However, the surgical technique may in some cases be more demanding than with conventional methods. Careful consideration of the pros and cons is therefore recommended in clinical practice. Biodegradable biomaterials complement the range of available treatment options in several fields of orthopedic surgery. However, some biomaterials performed worse than expected and were not recommended for clinical use, emphasizing the need for high-quality randomized trials. It is also noteworthy that several trials included only a limited number of patients, rendering the interpretation of the results of these underpowered studies challenging.

The healing capacity and osteogenesis pattern of demineralized dentin matrix (DDM)-fibrin glue (FG) compound

Demineralized dentin matrix (DDM) is an osteoconductive and osteoinductive material that has been successfully used in sinus floor augmentation and alveolar ridge augmentation in clinical applications. It releases bone morphogenetic proteins (BMPs) and other growth factors, making DDM a suitable grafting material. However, the granular particle of DDM makes it difficult to anchor into the bone defect area. The aim of this study was to investigate the biological effects and osteoinductivity of the combination of DDM and Fibrin Glue (FG) at an optimal ratio on bone healing from a critical bone defect in an animal model. The mouse osteoblastic cell line (MC3T3-E1) was co-cultured with various ratios of DDM and FG to examine their effects on osteoblast proliferation and differentiation, as indicated by alkaline phosphatase (ALP) activity, osteocalcin (OC) production and mineralized nodules formation. The optimal ratio was then chosen for further study with a rabbit calvarial defective model, in which they were implanted with DDM or DDM-FG1 (1 g: 0.1 ml) and DDM-FG2 (1 g: 0.5 ml) compounds, or left blank for 2, 4, 8 and 12 weeks to investigate soft tissue and new bone regeneration. Micro-CT and histology analysis were used to evaluate the total grafting properties according to the different healing periods. The result from in vitro studies demonstrated that the ratio of 1:0.1 induced more ALP activity and mineralized nodules, while the ratio of 1: 0.5 (DDM-FG combined) induced more osteocalcin (OC) at specific time points. In the animal model, the 3D new bone volume in all DDM-FG treatment groups was significantly greater than that in the blank group at 2, 4, 8 and 12 weeks. Furthermore, the new bone volume was greater in DDM-FG2 when compared to the other groups during the early weeks of the healing period. In histological analysis, clusters of osteoblasts were formed adjacent to the DDM particles, and newly formed bone was observed in all groups, suggesting an osteoinductive property of DDM. Moreover, the greater new collagen synthesis observed at 4 weeks suggested that early bone healing was induced in the DDM-FG2 group. This study demonstrated that at an optimal ratio, the DDM-FG compound enhances osteogenic activities and bone regeneration.

Use of platelet-rich fibrin (PRF) in the periodontology: A Review

Platelets play an essential role in wound healing and periodontal regeneration, so using platelet concentrates can speed up wound healing after periodontal treatment. Platelet-rich fibrin (PRF), an autogenous concentrated blood product, is a fibrin matrix comprising molecular and cellular elements that allow for optimum improvement and PRF also increases the production of osteoprotegerin, which causes osteoblast proliferation and acts as an osteoconductive and osteoinductive material, initiating bone regeneration. Platelet-rich plasma (PRP) and PRF are platelet concentrates prepared from the patient's own blood. Recent studies have focused on the development of therapeutic alternatives that are simple to prepare, non-toxic or biocompatible to living tissues, and inexpensive, with the potential to result in the local release of growth factors that accelerate hard and soft tissue healing. PRP is a plasma fraction that contains a high concentration of growth factors. PRF is a natural fibrin-based biomaterial derived from an anticoagulant-free blood harvest without any artificial biochemical modification, allowing fibrin membranes enriched with platelets and growth factors to be obtained. It facilitates the application of growth factors to the surgical area in a concentrated form, thereby accelerating wound improvement and regeneration. Platelet concentrates are used in many areas of dentistry, including soft tissue improvement, plastic periodontal surgery, gingival enlargement, ridge preservation, regeneration of bone defects, drug-related osteonecrosis of the jawbone, sinus augmentation, immediate implant placement, and implant osseointegration. Their use is preferred due to their ease of application and low cost. This paper reviews the current literature concerning the utilization of platelet-rich fibrin in periodontology. How to cite this article: Sağsöz A, Acun Kaya F. Use of platelet-rich fibrin (PRF) in periodontology: A review. J Med Dent Invest 2023;4:e230317. https://doi.org/10.5577/jomdi.e230317 Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

Engineering of immunoinstructive extracellular matrices for enhanced osteoinductivity.

The increasing recognition of the contribution of the immune system to activate and prime regeneration implies that tissue engineering strategies and biomaterials design should target regulation of early immunological processes. We previously proposed the cell-based engineering and devitalization of extracellular matrices (ECMs) as a strategy to generate implant materials delivering custom-defined signals. Here, in the context of bone regeneration, we aimed at enhancing the osteoinductivity of such ECMs by enriching their immunomodulatory factors repertoire. Priming with IL1β a cell line overexpressing BMP-2 enabled engineering of ECMs preserving osteoinductive signals and containing larger amounts of angiogenic (VEGF) and pro-inflammatory molecules (IL6, IL8 and MCP1). Upon implantation, these IL1β-induced materials enhanced processes typical of the inflammatory phase (e.g., vascular invasion, osteoclast recruitment and differentiation), leading to 'regenerative' events (e.g., M2 macrophage polarization) and ultimately resulting in faster and more efficient bone formation. These results bear relevance towards the manufacturing of potent off-the-shelf osteoinductive materials and outline the broader paradigm of engineering immunoinstructive implants to enhance tissue regeneration.

Hypoxia Drives Material-Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid-Loaded Macrophage Axis.

Heterotopic ossification (HO) is a double-edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materialsshows promising therapeutic potentials for bone regeneration. However, the mechanism of material-induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material-induced bone formation. Hypoxia inducible factor-1α (HIF-1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF-1α significantly inhibits M2 macrophage, subsequent osteoclast, and material-induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast-conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF-1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid-loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.

Osteoclasts may play key roles in initiating biomaterial-induced ectopic bone formation

Current studies have identified that biomaterials in the form of sintered calcium phosphate (CaP) ceramics with specific physicochemical properties can induce bone formation in heterotopic sites without additional cells or growth factors, termed osteoinductive biomaterials, which display great potential in repairing large segmental bone defects. However, the underlying mechanism of osteoinduction remains elusive, preventing the optimal design of biomaterials with better osteogenic potential. Recently, accumulative evidence has illustrated that osteoclasts could recruit mesenchymal stem cells (MSCs) and enhance osteogenic differentiation of MSCs by secreting various cytokines, such as collagen triple helix repeat containing 1 (CTHRC1), sphingosine-1-phosphate (S1P), and complement factor 3a (C3a) during bone remodeling. Interestingly, a recent study found that osteoclastogenesis occurred prior to the bone formation during biomaterial-induced ectopic bone formation, and bone formation was blocked once osteoclastogenesis was inhibited with the anti-RANKL antibody at the early stage, which suggest that osteoclasts may play a critical role in the osteoinduction. However, whether osteoclasts could initiate biomaterial-induced ectopic bone formation remains unclear. Consequently, for the first time, we hypothesize that osteoclasts formed in non-osseous environments are perceived as a “starting signal” and osteoclastogenesis is the initiator of biomaterial-induced ectopic bone formation, which may provide useful instruction for osteoinductive materials modification and benefit the development of treatment strategies for heterotopic ossification (HO) in the future.

Genesis of osteoclasts on calcium phosphate ceramics and their role in material-induced bone formation.

Innate immune responses play important roles in material-induced bone formation and such roles were further explored in the current study with an emphasis on M2 macrophages and osteoclastogenesis. With the presence of M-CSF and RANKL, M0 macrophages from FVB mouse bone marrow-derived monocytes (BMMs) fused to osteoclasts with both M2 marker and osteoclast marker at day 5, and such osteoclast formation at day 5 was enhanced when the cells were treated with IL-4 at day 3. With IL-4 treatment alone for 24 h, M0 polarized into M2 macrophages. Conditioned medium of M2 macrophages enhanced osteogenic differentiation of MC3T3-E1 (pre-osteoblasts) while osteoclast conditioned medium enhanced osteogenic differentiation of CRL-12424 (osteogenic precursors). TCPs (a typical osteoinductive material) supported M2 macrophage polarization at day 4 and osteoclast formation at day 5, while TCPb (a typical non-osteoinductive material) was less effective. Moreover, osteoclasts formed on TCPs produced osteogenic factors including S1P, Wnt10B and BMP-6, resulting osteogenic differentiation of CRL-12424 cells. Similar to in vitro testing, TCPs favored M2 macrophage polarization followed by the formation of osteoclasts in vivo, as compared to TCPb. The overall data provided evidence of a coupling between M2 macrophages, osteoclasts and material-induced bone formation: osteoclasts formed from M2 macrophages secrete osteogenic cytokines to induce osteogenic differentiation of osteogenic precursor cells to finally form bone. The current findings outlined a biological mechanism of material-induced bone formation and further rationalized the use of osteoinductive materials for bone regeneration. STATEMENT OF SIGNIFICANCE: This paper provides evidence for finding out the relationship between M2 macrophages, osteoclasts and osteogenesis in material-induced bone formation. It suggested that osteoinductive materials enhanced macrophage polarization to M2 macrophages which fuses to osteoclasts, osteoclasts subsequently secret osteogenic cytokines to differentiate finally osteogenic precursors to form bone in osteoinductive materials. The data supports scientifically the superiority of osteoinductive materials for bone regeneration in clinics.

Cooperative Calcium Phosphate Deposition on Collagen-Inspired Short Peptide Nanofibers for Application in Bone Tissue Engineering.

In recent years, immense attention has been devoted over the production of osteoinductive materials. To this direction, collagen has a dominant role in developing hard tissues and plays a crucial role in the biomineralization of these tissues. Here, we demonstrated for the first time the potential of the shortest molecular pentapeptide domain inspired from collagen toward mineralizing hydroxyapatite on peptide fibers to develop bone-filling material. Our simplistic approach adapted the easy and facile route of introducing the metal ions onto the peptide nanofibers, displaying adsorbed glutamate onto the surface. This negatively charged surface further induces the nucleation of the crystalline growth of hydroxyapatite. Interestingly, nucleation and growth of the hydroxyapatite crystals lead to the formation of a self-supporting hydrogel to construct a suitable interface for cellular interactions. Furthermore, microscopic and spectroscopic investigations revealed the crystalline growth of the hydroxyapatite onto peptide fibers. The physical properties were also influenced by this crystalline deposition, as evident from the hierarchical organization leading to hydrogels with enhanced mechanical stiffness and improved thermal stability of the scaffold. Furthermore, the mineralized peptide fibers were highly compatible with osteoblast cells and showed increased cellular biomarkers production, which further reinforced the potential application toward effectively fabricating the grafts for bone tissue engineering.

A composite, off-the-shelf osteoinductive material for large, vascularized bone flap prefabrication

We previously described an immortalized, genetically-engineered human Mesenchymal stromal cell line to generate BMP2-enriched Chondrogenic Matrices (MB-CM), which after devitalization and storage could efficiently induce ectopic bone tissue by endochondral ossification. In order to increase the efficiency of MB-CM utilization towards engineering scaled-up bone structures, here we hypothesized that MB-CM can retain osteoinductive properties when combined with an osteoconductive material. We first tested different volumetric ratios of MB-CM:SmartBone® (as clinically used, osteoconductive reference material) and assessed the bone formation capacity of the resulting composites following ectopic mouse implantation. After 8 weeks, as little as 25% of MB-CM was sufficient to induce bone formation and fusion across SmartBone® granules, generating large interconnected bony structures. The same composite percentage was then further assessed in a scaled-up model, namely within an axially-vascularized, confined, ectopically prefabricated flap (0.8 cm3) in rats. The material efficiently induced the formation of new bone (31% of the cross-sectional area after 8 weeks), including bone marrow and vascular elements, throughout the flap volume. Our findings outline a strategy for efficient use of MB-CM as part of a composite material, thereby reducing the amount required to fill large spaces and enabling utilization in critically sized grafts, to address challenging clinical scenarios in bone reconstruction. Statement of significanceMost bone repair strategies rely either on osteconductive properties of ceramics and devitalized bone, or osteoinductive properties of growth factors and extracellular matrices (ECM). Here we designed a composite material made of a clinically accepted osteoconductive material and an off-the-shelf tissue engineered human cartilage ECM with strong osteoinductive properties. We showed that low amount of osteoinductive ECM potentiated host cells recruitment to form large vascularized bone structures in two different animal models, one being a challenging prefabricated bone-flap model targeting challenging clinical bone repair. Overall, this study highlights the use of a promising human off-the-shelf material for accelerated healing towards clinical applications.

P7. Percutaneous delivery of recombinant human bone morphongenetic protein-2 augments fusion in a nicotine impaired rabbit fusion model

<h3>BACKGROUND CONTEXT</h3> Several experiments have shown that delivery of BMP-2 in a delayed fashion from initial surgery may be superior for optimal bone growth. Studies of posterolateral spinal fusion in rabbits have shown that BMP-2 expression physiologically peaks from 4-6 weeks out from surgery. The hypothesis of this experiment was that delayed delivery of ACS/BMP-2 would augment bone growth in a rabbit spine fusion model. By percutaneously delivering ACS/BMP-2 we would be able to deliver osteoinductive material at an optimal time point away from the typical time of surgery application. <h3>PURPOSE</h3> To determine if controlled delivery of morselized absorbable collagen sponge (ACS) Rh-BMP2 in a delayed manner postsurgery would allow for increased fusion mass in a rabbit spine fusion model. <h3>STUDY DESIGN/SETTING</h3> A nicotine-impaired spinal fusion rabbit model. <h3>PATIENT SAMPLE</h3> Sixteen male one-year-old rabbits. <h3>OUTCOME MEASURES</h3> Histologic, radiologic (radiographic, CT scans) and palpation examinations were performed to determine fusion status and the volume of bone formed. <h3>METHODS</h3> Sixteen male one-year-old rabbits underwent a posterolateral spinal fusion with iliac crest bone graft at L5-L6 while being given nicotine to prevent spinal fusion as previously published. Eight were controls while 8 had morselized RhBMP-2 (4.2mg) injected at the fusion site at 4 weeks postoperatively. At 12 weeks, the rabbits were sacrificed. Histologic, radiologic (radiographic, CT scans) and palpation examinations were performed to determine fusion status and the volume of bone formed. Hematoxylin and eosin (H&E) stain were used for histology. There were 4 of 8 rabbits in the control cohort with bilateral fusion and 6 of 8 rabbits in the BMP-DDC that had bilateral fusion based on CT scan analysis. A student's t-test was used to compare the CT scan measured volume of bone created between control (CC) and RhBMP-2 delayed delivery cohorts (BMP-DDC). <h3>RESULTS</h3> Seven of 8 rabbits in the BMP-DDC and 5 of 8 rabbits in the CC formed definitive fusion with a positive palpation exam, bridging bone between transverse processes on CT scan and an x-ray showing fusion. Histologic analysis revealed new remodeled bone within the BMP-DDC. There was increased average volume of bone formed within the BMP-DDC vs the CC (22.6±13.1 vs 11.1±3.6 cm^3, p=0.04) <h3>CONCLUSIONS</h3> Our study shows that injectable morselized ACS/RhBMP-2 can create twice as much bone within a nicotine-impaired rabbit spine fusion model when delivered 4 weeks out from time of surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Effects of Platelet-Rich Osteoconductive-Osteoinductive Allograft Compound on Tunnel Widening of ACL Reconstruction: A Randomized Blind Analysis Study.

The anterior cruciate ligament (ACL) is a commonly injured ligament in the knee. Bone tunnel widening is a known phenomenon after soft-tissue ACL reconstruction and etiology and the clinical relevance has not been fully elucidated. Osteoconductive compounds are biomaterials providing an appropriate scaffold for bone formation such as a demineralized bone matrix. Osteoinductive materials contain growth factors stimulating bone lineage cells and bone growth. A possible application of osteoinductive/osteoconductive (OIC) material is in ACL surgery. We hypothesized that OIC placed in ACL bone tunnels: (1) reduces tunnel widening, (2) improves graft maturation, and (3) reduces tunnel ganglion cyst formation. To test this hypothesis, this study evaluated the osteogenic effects of demineralized bone matrix (DBM) and platelet-rich plasma (PRP) on tunnel widening, graft maturation, and ganglion cyst formation. This was a randomized controlled clinical trial pilot study. A total of 26 patients that elected to have ACL reconstruction surgery were randomized between the OIC and control group. Measurements of tunnel expansion and graft-tunnel incorporation were conducted via the quantitative image analysis of MRI scans performed at six months after surgery for both groups. No patients had adverse post-operative reactions or infections. The use of OIC significantly reduced tunnel widening (p < 0.05) and improved graft maturation (p < 0.05). Patients treated with OIC had a significantly lower prevalence of ganglion cyst compared to the control group (p < 0.05). The use of OIC has measurable effects on the reduction of tunnel widening, improved graft maturation, and decreased size of ganglion cyst after ACL reconstruction. This study explored the utilization of biologics to minimize bone tunnel widening in ACL reconstruction surgery.

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo.

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.

Auto-tooth bone graft material for reconstruction of bone defects in the oral region: case reports

We present some clinical cases of autogenous tooth graft - a modern method in which the extracted teeth are processed into a demineralised dentin matrix (DDM) and are then immediately transplanted into the post-extraction sockets or bone defects.

Combined treatment of giant cell bone tumor

Introduction. Giant cell tumor refers to tumors with an uncertain malignancy potential, has a locally aggressive course. Intra-focal resections performed for a giant cell tumor of long tubular bones are accompanied by the development of relapse in 30–46 % of cases. The combination of pathogenetic therapy with surgical intervention makes it possible to reduce the frequency of relapses in operable tumors after marginal and intra-focal resections, and in inoperable tumors to provide local control and relieve pain. Objective – to analyze the results of combined treatment of patients with giant cell bone tumor. Materials and methods. In the conditions of Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Tatarstan, 13 patients aged 20 to 63 years are in the process of combined treatment of a giant cell tumor. As of November 2021, 7 patients have completed treatment.Results. Among the 7 patients who completed treatment, 6 people were operated on (1 patient refused surgery). In 5 patients, intra-focal resection of the tumor with osteoinductive material “BoneMedic-S” was performed, in 1 patient with a giant cell tumor of the sciatic bone, resection of the sciatic bone was performed without reconstruction. 1 patient with a widespread tumor (sacral lesion) receives supportive treatment. Conclusion. The combined approach in the treatment of giant-cell bone tumor allows performing a functional-saving, organpreserving surgical intervention, significantly reducing the risk of tumor recurrence and its malignant transformation.

Hydroxyapatite formation under calcium-deficient concentration conditions modulated by amino acid-capped gold nanoparticles

This study investigated the effects of the surface modification of gold nanoparticles (AuNPs) with negative, positive, and polar uncharged amino acids on hydroxyapatite formation under calcium-deficient conditions. The AuNPs were prepared using a chemical reduction method and capped with eight different amino acids. The different amino acid (AA) side chains had different interactions with the AuNPs, as indicated by the different shifts in the ultraviolet–visible spectra. The calcium and phosphor sources were added at the same concentration to obtain calcium-deficient hydroxyapatite (CDHA). X-ray diffraction revealed the presence of amino acid-capped AuNPs during synthesis resulting in CDHA with low crystallinity. The calculated crystallinity index (CI) indicated that aspartic acid could promote the crystallization of biomimetic hydroxyapatite. The crystallite size decreased by 6%–62%, which is beneficial for osteoinductivity in bone substitute applications. The involvement of AA-AuNPs in the synthesized hydroxyapatite resulted in apatite with a higher Ca/P ratio than that of the control except for cysteine, lysine, and glutamine. The morphology of the samples ranged from quasi-spherical to needle-like, which can potentially be used as an osteoinductive material.