Long-Term Safety of Bone Regeneration Using Autologous Stromal Vascular Fraction and Calcium Phosphate Ceramics: A 10-Year Prospective Cohort Study.

This prospective cohort study aimed to assess long-term safety, dental implant survival, and clinical and radiological outcomes after maxillary sinus floor elevation (MSFE; lateral window technique) using freshly isolated autologous stromal vascular fraction (SVF) combined with calcium phosphate ceramics. All 10 patients previously participating in a phase I trial were included in a 10-year follow-up. They received either ß-tricalcium phosphate (ß-TCP; n = 5) or biphasic calcium phosphate (BCP; n = 5) with SVF-supplementation on one side (study). Bilaterally treated patients (6 of 10; 3 ß-TCP, 3 BCP) received only calcium phosphate on the opposite side (control). Clinical and radiological assessments were performed on 44 dental implants at 1-month pre-MSFE, and 0.5- to 10-year post-MSFE. Implants were placed 6 months post-MSFE. No adverse events or pathology was reported during a 10-year follow-up. Forty-three dental implants (98%) remained functional. Control and study sides showed similar peri-implant soft-tissue quality, sulcus bleeding index, probing depth, plaque index, keratinized mucosa width, as well as marginal bone loss (0-6 mm), graft height loss (0-6 mm), and graft volume reduction. Peri-implantitis was observed around 6 implants (control: 4; study: 2) in 3 patients. This study is the first to demonstrate the 10-year safety of SVF-supplementation in MSFE for jawbone reconstruction. SVF-supplementation showed enhanced bone regeneration in the short term (previous study) and led to no abnormalities clinically and radiologically in the long term.

[Evaluation of the effect of cattle calcined bone grafting material to repair alveolar bone defect after tooth extraction].

PURPOSE: To verify the efficacy and safety of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction. METHODS: A randomized, bind, parallel, positive-control multicenter clinical trial was conducted. A total of 280 subjects were randomly assigned to either the experimental group (calcined cattle bone group) or control group (Bio-Oss group) equally. The main efficacy indicator was the imaging changes 24 weeks after material implantation. Secondary efficacy indicators were wound healing, rejection, bone metabolism, post-filling symptoms and signs of bone infection. The safety of material was assessed by the incidence of adverse events and serious adverse events. SAS 8.2 software package was used for statistical analysis. RESULTS: A total of 280 cases were included, of them 267 cases completed the study while 13 cases fell off. The effective rate of FAS(PPS) was 90.58%(97.46%) in the experimental group and 87.05% (95.04%) in the control group. The difference of effective rate between the experimental group and control group (95%CI) was 3.53% (-3.88%, 10.94%) of FAS, 2.42% (-2.38%, 7.22%) of PPS, and there was no significant difference between the two groups. The incision healing of the two groups was good, and the incidence of rejection, bone infection signs, post-filling symptoms and bone metabolic changes was very low. The incidence of adverse events was similar in the two groups, and no serious adverse events related to the study materials occurred. CONCLUSIONS: The efficacy of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction is not inferior to that of Bio-Oss, and it is safe and effective for alveolar bone defect repair.

The use of 3D ceramic block graft compared with autogenous block graft for rehabilitation of the atrophic maxilla: a randomized controlled clinical trial.

BACKGROUND: Dental implant placement may require a bone graft for vertical and horizontal alveolar ridge augmentation. Due to its osteoconduction, osteoinductive, and osteogenesis, autogenous bone graft characteristics are considered the standard gold treatment. However, autografts can promote postoperative morbidity and implicate difficulties concerning the graft adaptation to the recipient's bone since it can eventually avoid gaps. To overcome these issues, this trial will compare the performance of Plenum® Oss 3Dß fit, an alloplastic graft, and a 3D-printed patient-specific graft based on ß-tricalcium phosphate to the autograft procedure. METHODS: This is a split-mouth randomized clinical study designed to evaluate the performance of personalized (patient-specific) bioceramic bone grafts (Plenum® Oss 3Dß fit) for bone augmentation of the atrophic anterior maxilla in comparison to the autogenous bone graft. We hypothesize that the gain and maintenance of the grafted area volume and the quality of the newly formed bone tissue after eight months postoperative with the synthetic patient-specific graft will be superior to the autogenous bone graft. To assess the quantity and the quality of bone neoformation, volumetric and histological analyses will be performed. DISCUSSION: The fabrication of medical devices by additive manufacturing presents advantages over conventional manufacturing processes, mostly related to the precision of geometry and anatomy. Additionally, the osteoconductive proprieties of ß-tricalcium phosphate enable this synthetic bone substitute as an alternative solution over autogenous graft for bone defect reconstruction. Thus, patient-specific bone grafts can potentially improve patient satisfaction, reducing the need for autogenous bone grafts, consequently avoiding implications related to this type of treatment, such as patient morbidity. TRIAL REGISTRATION: This study is registered in REBEC (Registro Brasileiro de Ensaios Clínicos): RBR-76wmm3q; UTN: U1111-1272-7773. Registration date: 14 September 2021.

Severe Complications Following Maxillary Sinus Augmentation Using Poly L-lactide-co-ε-caprolactone-Coated Bovine Bone: A Retrospective Study.

PURPOSE: To describe the postoperative complications following lateral wall sinus augmentation using (poly L-lactideco-ε-caprolactone; PLCL) and natural polysaccharides polymers-coated bovine bone (PBB). The secondary aims were to examine histologic findings and to propose complication management alternatives. MATERIALS AND METHODS: This retrospective study included 61 subjects who underwent 67 lateral wall sinus augmentation procedures using PBB in the standard protocol. In cases that presented complications, treatment included additional antibiotic therapy, implant removal, or sinus reentry and total removal of the grafting material. In three cases, biopsy specimens were taken from the sinuses, and histologic analyses were performed. RESULTS: The prevalence of postoperative complications was 32.8% (22 of 67 cases) in 18 of the patients (29.5%). The most prevalent symptoms were persistent pain (68.2%), swelling (63.6%), and oroantral fistula (54.5%). Radiographic signs appeared in 45.5% of the complications. A total of 24 implants failed; thus, an overall 80.3% survival rate was established at 19 months. The vast majority of complications (86.4%) were treated eventually with reentry surgery and revealed that the sinus was full with granulation tissue surrounding pieces of a nonossified rubber-like material. In cases where implants were placed, nonosseointegrated implants were surrounded by soft tissue. The sinus was cleaned thoroughly; the graft material remnants were removed together with inflamed parts of the sinus membrane, followed by chlorhexidine and saline lavages. In the biopsy specimens taken from the sinus cavity, there were no histologic features of new bone formation around the grafted material. CONCLUSION: Lateral wall maxillary sinus augmentation using PBB was associated with an acute sinus infection histologic appearance and with a 7-times-higher failure rate compared with previous reports. This serious adverse event suggests that PBB cannot be recommended for maxillary sinus augmentations.

Orbital reconstruction - applied materials, therapeutic agents and clinical problems of restoration of defects.

Reconstruction of large cavities in the skull and facial regions is important not only to restore health but also for the correction of facial distortions. Every visible deformity in the facial region of the patient affects their mental wellness and perception by society, entailing both, deterioration of health, but also a decrease in the performance in society, which translates into its productivity. With the progressive degradation of the natural environment, cancer, in the coming years, will be on the leading causes of morbidity and mortality. The review focuses on two main aspects: (i) the causes of injuries leading to the necessity of removal of orbital cavities occupied by the tumor and then their reconstruction, with the focus on the anatomical structure of the orbital cavity, (ii) the materials used to reconstruct the orbital cavities and analyze their advantages and disadvantages. The manuscript also underlines the not yet fully met challenges in the area of facial- and craniofacial reconstruction in people affected by cancer.

Comparison of post-operative outcomes of graft materials used in reconstruction of blow-out fractures.

BACKGROUND: Trauma to the face caused by assault or impact may cause internal orbital fracture. Increased intraorbital pressure without disruption of soft tissue integrity or causing a fracture line in orbital rims or orbital floor fractures described as 'orbital blow-out fracture'. Such fractures have been categorized as 'pure blow-out fractures' in which only the orbital floor is affected, and 'impure blow-out fractures' in which other maxillofacial bones such as zygoma, maxilla and nasoethmoid are also affected. Physical examination reveals periorbital edema and ecchymosis, subconjunctival hemorrhage, limitation of eye globe movements, diplopia, enophthalmos, dystopia, and infraorbital hypoesthesia. Reconstruction of the orbital bony structures is the most important issue to preserve the standard orbital functions and providing an aesthetic view. Although many surgical approaches have been defined in the literature regarding the attitude and timing of treatment, no consensus exists. In literature; many autogenous and alloplastic biomaterials have been recommended to correct orbital bone defects. METHODS: This study aims to compare postoperative outcomes of patients presenting with pure and impure blow-out fractures repaired with cartilage, bone grafts, titanium mesh or porous polyethylene implant. Sixty-four orbital floor fractures of 62 cases were included in this research who admitted to our clinic with maxillofacial trauma between 2011 and 2018. All patients underwent maxillofacial radiological examination; Waters radiography and also axial-coronal plane maxillofacial and orbital computerized tomography. RESULTS: Permanent, post-operative, vertical diplopia in extreme gazes was detected in 3 of 14 patients in whom the orbital floor was reconstructed with an iliac bone graft. Two of nineteen cases who underwent reconstruction using auricular conchal cartilage graft had vertical diplopia in extreme gazes four months after the operation. The implant extruded and became palpable in 2 of 15 patients in the porous polyethylene implant group. None of the patients in the iliac bone and conchal cartilage autograft groups was presented late postoperative enophthalmos according to the graft resorption. In titanium mesh group, 1 of eleven patients had permanent, post-operative vertical diplopia in extreme gazes. None of the patients in this group developed any donor area complications, infection, or implant extrusion. CONCLUSION: Results show that the auricular conchal cartilage graft was the best biomaterial used to repair defects smaller than 4 cm², where as titanium mesh was a good option to repair defects larger than 4 cm². However, selection of the optimal biomaterial to be used to repair orbital blow-out fractures should be made according to patient characteristics and preoperative findings, the severity of the injury, the cost of the biomaterial to be used, and surgeon's expertise.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

Iatrogenic risk of osteonecrosis of the jaw? Bone substitutes for dental implants: a warning from Japan.

Commercial bone substitutes that are widely used for bone augmentation for dental implants are predisposing factors in the development of osteonecrosis of the jaw (ONJ), overlooking this situation may lead to serious problems. Most of these materials are supplied as inorganic porous granules of calcium phosphate, which have characteristics that exceed the bone resorption ability of normal osteoclasts; therefore, they can be equally regarded as existing antiresorptive necrotic bony granules in the body, i.e., micro-ONJs. In addition, because dental implants directly contact the surrounding bone without the periodontium with immunoprotective functions, the mucosal penetration of the dental implant itself predisposes the underlying bone to the risk of infection, latent osteomyelitis, and ONJ. Therefore, the remaining porous granules surrounding the dental implant pose an additional iatrogenic risk, even though the tissue may appear superficially healthy. In an aging society, an individual who was systemically healthy at the time of implantation with bone augmentation could develop osteoporosis or cancer bone metastasis later in life. ONJ can occur more easily if an antiresorptive agent such as bisphosphonates or denosumab is administered without sufficiently recognizing an intraoral situation. If the latent risk is known in advance, the selection or use of medicines could be restricted. Such restrictions can result in other crucial issues that are beyond the discretion of the dentists; however, dentists have not been warned about such possibilities. The use of antiresorptive agents and bone substitutes for dental implants should be reconsidered to avoid numerous adverse events such as ONJ.

A bioceramic scaffold composed of strontium-doped three-dimensional hydroxyapatite whiskers for enhanced bone regeneration in osteoporotic defects.

Reconstruction of osteoporotic bone defects is a clinical problem that continues to inspire the design of new materials. Methods: In this work, bioceramics composed of strontium (Sr)-doped hydroxyapatite (HA) whiskers or pure HA whiskers were successfully fabricated by hydrothermal treatment and respectively named SrWCP and WCP. Both bioceramics had similar three-dimensional (3D) porous structures and mechanical strengths, but the SrWCP bioceramic was capable of releasing Sr under physiological conditions. In an osteoporotic rat metaphyseal femoral bone defect model, both bioceramic scaffolds were implanted, and another group that received WCP plus strontium ranelate drug administration (Sr-Ran+WCP) was studied for comparison. Results: At week 1 post-implantation, osteogenesis coupled blood vessels were found to be more common in the SrWCP and Sr-Ran+WCP groups, with substantial vascular-like structures. After 12 weeks of implantation, comparable to the Sr-Ran+WCP group, the SrWCP group showed induction of more new bone formation within the defect as well as at the implant-bone gap region than that of the WCP group. Both the SrWCP and Sr-Ran+WCP groups yielded a beneficial effect on the surrounding trabecular bone microstructure to resist osteoporosis-induced progressive bone loss. While an abnormally high blood Sr ion concentration was found in the Sr-Ran+WCP group, SrWCP showed little adverse effect. Conclusion: Our results collectively suggest that the SrWCP bioceramic can be a safe bone substitute for the treatment of osteoporotic bone defects, as it promotes local bone regeneration and implant osseointegration to a level that strontium ranelate can achieve.

Complete regeneration of large bone defects in rats with commercially available fibrin loaded with BMP-2.

This study aimed at investigating in vitro and in vivo the efficiency of commercially available fibrin as a carrier for controlled and sustained bone morphogenetic protein-2 (BMP-2) release to induce bone formation and reduce the side effects of its use. In vitro release and activity of low-dose recombinant human BMP-2 (rhBMP-2) (37.5 µg/mL) embedded in commercially available fibrin were evaluated and, subsequently, critical-size femur defects in rats were grafted to study bone regeneration and vascularisation by micro-computed tomography (µCT) and histology. In vitro experiments showed a sustained BMP-2 release with a high BMP activity remaining after 28 d. In vivo, fibrin loaded with BMP-2 showed an extremely fast bone healing, with a large amount of new bone formation throughout the entire defect in the first 4 weeks and complete cortical repair and fusion after 8 weeks, with no ectopic bone formation. In contrast, the control fibrin group did not fuse after 12 weeks. Vascularisation was similar in both groups at 4 and 12 weeks after implantation. In conclusion, commercially available fibrin is a very efficient carrier for rhBMP-2 to graft critical-size cortical bone defects and might be a more optimal delivery vehicle for BMP-2-induced bone regeneration than currently available collagen sponges.

Maxillary sinus floor elevation using Beta-Tricalcium-Phosphate (beta-TCP) or natural bone: same inflammatory response.

Sinus elevation is a common procedure to increase bone volume in the atrophic maxilla to allow placement of dental implants. Autogenous bone is the gold standard but is limited in quantity and causes morbidity at the donor site. ß-TCP is a synthetic biomaterial commonly used in that purpose. It appears to induce a poor inflammatory response. This study aimed to evaluate the degree of edema of the sinus mucosa after sinus lift surgery according to the type of biomaterial. Forty sinuses (20 patients) were included retrospectively and divided into 2 groups according to the biomaterial that was used: synthetic biomaterial (BTCP group), natural bone (BONE group). A control group (CTRL group) was constituted by the non-grafted maxillary sinuses. Twelve measurements per sinus were realized on pre- and post-operative computed tomography and averaged to provide the sinus membrane thickness value (SM.Th). SM.Th was thicker post-operatively in the BTCP and BONE groups in comparison with the CTRL group and in comparison with pre-operative measurements. No difference was found post operatively between the BTCP and BONE groups. We found that a synthetic biomaterial (ß-TCP) induced the same degree of edema, and thus of inflammation, as natural bone. It constitutes therefore an interesting alternative to autogenous bone for maxillary sinus lifts.

Synthetic Blocks for Bone Regeneration: A Systematic Review and Meta-Analysis.

This systematic review is aimed at evaluating the effectiveness of synthetic block materials for bone augmentation in preclinical in vivo studies. An electronic search was performed on Pubmed, Scopus, EMBASE. Articles selected underwent risk-of-bias assessment. The outcomes were: new bone formation and residual graft with histomorphometry, radiographic bone density, soft tissue parameters, complications. Meta-analysis was performed to compare new bone formation in test (synthetic blocks) vs. control group (autogenous blocks or spontaneous healing). The search yielded 214 articles. After screening, 39 studies were included, all performed on animal models: rabbits (n = 18 studies), dogs (n = 4), rats (n = 7), minipigs (n = 4), goats (n = 4), and sheep (n = 2). The meta-analysis on rabbit studies showed significantly higher new bone formation for synthetic blocks with respect to autogenous blocks both at four-week (mean difference (MD): 5.91%, 95% confidence intervals (CI): 1.04, 10.79%, p = 0.02) and at eight-week healing (MD: 4.44%, 95% CI: 0.71, 8.17%, p = 0.02). Other animal models evidenced a trend for better outcomes with synthetic blocks, though only based on qualitative analysis. Synthetic blocks may represent a viable resource in bone regenerative surgery for achieving new bone formation. Differences in the animal models, the design of included studies, and the bone defects treated should be considered when generalizing the results. Clinical studies are needed to confirm the effectiveness of synthetic blocks in bone augmentation procedures.

Clinical and radiographic evaluation of bioactive glass in posterior cervical and lumbar spinal fusion.

INTRODUCTION: Spinal surgery of degenerative painful segments is a valuable treatment option in the management of chronic cervical and low back pain. The surgery consists in stabilizing and fusing painful vertebral segment(s). The objective of the study was to report our experience with 45S5 bioactive glass (BAG) to obtain inter-vertebral fusion in the context of posterior spine surgery. MATERIAL AND METHOD: In this retrospective study, 30 patients with a wide range of degenerative and traumatic conditions of the cervical or lumbar spine underwent spinal fusion utilizing a synthetic bone graft substitute of BAG (GlassBone™, Noraker, Lyon-Villeurbanne, France). The pain was evaluated by VAS score, and graft consolidation was assessed on according radiographic images at 1-year post-op. RESULTS: All patients underwent posterior spinal fusion either in the cervical or the thoraco-lumbar spine. Multi-level fusions represented the majority of the cohort (43% of patients with more than seven levels treated). Radiographic imaging demonstrated excellent fusion rates (93%) at final follow-up, equivalent to the outcomes reported in the literature for autogenous bone, with excellent bone bridging and no spinal implant loosening. Only two cases of non-union were encountered. Additionally, 90% of the patients demonstrated recovery at 1 year after surgery with a pain reduction of 60%. CONCLUSION: The results of this retrospective study suggest that the 45S5 BAG may be an interesting alternative option to autologous graft, in terms of safety and bone fusion efficiency. LEVEL OF EVIDENCE: IV Retrospective study.

Biomaterial-induced multinucleated giant cells express proinflammatory signaling molecules: A histological study in humans.

The biomaterials physicochemical characteristics influence their cellular reaction, degradation and regenerative capacities. Macrophages and multinucleated giant cells (MNGCs) are observed in the augmentation area of biomaterials. This study, for the first time, evaluated the polarization pattern of macrophages and MNGCs in response to two different bone substitute materials (synthetic bone substitute material [SBSM] = NanoBone vs. xenogeneic bone substitute material [XBSM] = Bio-Oss) in human bone biopsies compared to non-augmented bone (control). Histomorphometrical analysis of the polarization in proinflammatory (M1) and anti-inflammatory (M2) cells was performed using different immunohistochemical markers: CD-68 = macrophages; CCR-7 and Cox-2 (M1) and CD-206 and CD-163 (M2) and tartrate-resistant acid phosphatase (TRAP). The macrophage polarization pattern in SBSM showed a significantly higher number of M1 cells than did XBSM and non-augmented bone. XBSM induced a significantly higher number of CD-206-positive macrophages than SBSM did. No significant difference was found between XBSM and the non-augmented bone. MNGCs expressed CD-68 and TRAP. In both test-groups, MNGCs showed a high proinflammatory character (CCR-7 and Cox-2-positive) and their number in the SBSM group was significantly higher than that of XBSM. The tissue distribution showed a significantly low percentage of the remaining biomaterial in SBSM compared to XBSM. Within the limitations of this study, these findings show that MNGCs exhibit a rather proinflammatory character and lead to biomaterial degradation, once they are induced in a high number. The premature degradation of bone substitute materials is compensated with a high percentage of connective tissue and not new bone formation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 780-790, 2019.

Results of the Induced Membrane Technique in the Management of Traumatic Bone Loss in the Lower Limb: A Cohort Study.

OBJECTIVE: To present our technique and early results using the Masquelet technique. DESIGN: Retrospective cohort study. PATIENTS/PARTICIPANTS: Thirteen patients with 14 open fractures of the femur and tibia were included between November 2013 and December 2014. INTERVENTION: A Masquelet technique was used to manage the open fractures. MAIN OUTCOME MEASURE: Infection and union rate. RESULTS: The mean follow-up was 17 months. The mean bone defect was 56.6 mm. Eight fractures (57.1%) progressed to union at an average of 42.1 weeks. Infection developed in 3 fractures (21.4%). Overall, the induced membrane technique was abandoned in 5 (35.7%) cases. CONCLUSIONS: The induced membrane technique showed a substantial rate of failure in the acute trauma setting in the lower limb. In the absence of sound published evidence, the authors now use the technique in selected cases only. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

[Use of the Peptigel with Nanofibres in the Bone Defects Healing]. / Vyuzití peptigelu s nanovlákny k lécbe defektu kostní tkáne.

INTRODUCTION Traumatic bone injuries or pathological processes may sometimes result in very extensive bone defects. Currently, the standard procedure applied in clinical humane as well as veterinary medicine to fill a bone defect is the autogenous bone graft which, however, necessitates a more invasive procedure for the patient and in the cases of extensive defects it fails to provide adequate amount of graft. Synthetic bone replacements can be used with no further burden for the patient and can simultaneously be used as the carriers for bioactive molecules or therapeutic drugs. For clinical use, an easy and simple application is one of the requirements that have to be taken into consideration. These requirements are best satisfied by preparations in the form of gel, which may be injected into the defects of various shapes even through minimal surgical approach. MATERIAL AND METHODS Synthetic transparent PGD-AlphaProA hydro-peptide-gel was used as a basis to develop a composite hydrogel scaffold. This gel was enriched by cryogenically ground poly- -caprolactone nanofibers (PCL) in a ratio of 1 ml of gel to 16 µg of nanofibres. In experimental animals (laboratory rat Wistar, n=20), a single regular circular defect of 1.5 mm in diameter was drilled by a low speed drill machine across the whole width of distal femur diaphysis, identically in both the hind legs. In the right hindleg, this defect was filled by injection of 0.05 ml of the composite peptide gel with nanofibers (experimental defect). In the contralateral limb a similar defect was left untreated, without filling (control defect), for spontaneous healing. The group of experimental animals was subsequently divided into four sub-groups (A, B, C, D) for the purpose of further follow-up. One week after the surgical implantation, in the first group of experimental animals (Group A; n = 5) lege artis euthanasia was performed, a radiological examination of both the hind legs was carried out and a sample of the bone from both the control and experimental defect was collected for histologic examination. The other groups of experimental animals were evaluated similarly at 2, 4 and 6 weeks after the surgical procedure (Group B, C, D; n = 5). These groups of experimental animals were assessed using various histological techniques by two independent pathologists. RESULTS A difference between the control and the experimental bone defect was observed only at the healing stage at two weeks after the implantation, when a tendency for greater formation of new bone trabeculas was seen in the defect treated with the composite hydro-peptide-gel with PCL nanofibers. The results show a slightly higher angiogenesis and cellularity at the bone defect site with an increase of newly formed bone tissue and faster colonisation of lamellar bone structures by bone marrow cells at early stages of the healing process (1-2 weeks old defect). In the experimental and control groups, at the later stage of healing (4-6 weeks old defect), the process of healing and bone modelling at the defect site shows no detectable morphological differences. CONCLUSIONS The experimental use of hydro-peptide-gel with PCL nanofibers in vivo in laboratory rats shows very good applicability into the defect site and, compared to the untreated defect within two weeks after the implantation, accelerates the bone healing. This fact could be an advantage especially at the early stage of healing, and thus accelerate the healing of more extensive defects. Key words: peptide gel, polycaprolactone, PCL, replacement, bone, healing, scaffold, nanofibers, biomaterial.

Hydroxyapatite cranioplasty: a retrospective evaluation of osteointegration in 17 cases.

BACKGROUND: Cranial reconstruction with autologous bone is still the gold standard although several biomaterials are available to re-establish the integrity of the cranial vault. Due to their biological and morphological characteristics, hydroxyapatite implants show promising results in small clinical cohort studies, especially within the paediatric population. Its biocompatibility and osteoconductivity should allow the formation of osseous bridging at the skull-prosthesis interface. OBJECTIVE: To examine the possible occurrence of osteointegration and to quantify it. METHODS: A retrospective study of patients with a hydroxyapatite implant from 2010 to 2014 at our neurosurgical department was conducted. Demographic, surgical and radiological data were studied. A senior neuroradiologist, a staff member neurosurgeon and a resident neurosurgeon independently performed the radiological evaluation. A new software analysis technique was developed to objectively quantify the degree of osteointegration. RESULTS: Seventeen implants were evaluated with an average patient age of 39 years and a mean follow-up of 155 weeks. Through radiologic evaluation, osseous bridging was deemed higher than 50% in six prostheses and higher than 75% in three. In five patients, no osteointegration could be seen. The remaining patients exhibited sparse signs of osteointegration, estimated between 10 and 50%. Software analysis showed an average osteointegration ratio of 37.4% with a 400-HU filter and 27.3% with a 700-HU filter. CONCLUSION: In this small retrospective study of cranial hydroxyapatite implants, osteointegration did occur and to a degree of more than 50% in 1/3 of the patients.

Role of the Complement System in the Response to Orthopedic Biomaterials.

Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device.

Complications with PMMA compared with other materials used in cranioplasty: a systematic review and meta-analysis.

Polymethyl methacrylate (PMMA) has been considered a suitable material for cranioplasty. However, no consensus has been reached concerning the best material for cranioplasty with regard to minimizing complications. Thus, this systematic review and meta-analysis aimed to compare the complication rates of PMMA with those of autologous bone and titanium mesh. This review was registered with PROSPERO (CRD42016042725). Systematic searches were conducted on PubMed/MEDLINE, Scopus, and Web of Science. The focus question was, "Do PMMA prostheses used in cranioplasty have complications rates similar to those of autologous bone and titanium mesh?" A meta-analysis of complication rates was performed on the basis of dichotomous outcomes assessed by risk ratio (RR) with corresponding 95% confidence intervals (CI). From 1014 data sources, 11 articles were selected according to eligibility criteria. These articles involved 1,256 individuals and 1,278 cranioplasties using autologous bone (n = 408), PMMA (n = 379), or titanium (n = 151). The follow-up period ranged from 63 days to 54.3 months. No difference was observed between the complication rates of PMMA and autologous bone (p = 0.94; RR, 0.98; 95%CI, 0.54-1.75) or between PMMA and titanium (p = 0.38; RR, 1.59; 95%CI, 0.57-4.48). Sub-analysis of the reasons for craniotomy (trauma/non-trauma) was conducted, which revealed no significant difference (p = 0.91; RR, 0.95; 95%CI, 0.37-2.42). The meta-analysis indicated that the use of PMMA yields complication rates that are near those of autologous bone and titanium mesh.

Treatment outcomes of the simple bone cyst: A comparative study of 2 surgical techniques using artificial bone substitutes.

Simple bone cysts (SBCs) are benign lesions of unknown etiology. Because of its high relapse rate, they occasionally need a long period of treatment and restriction of activities in children and adolescent. Although various treatment modalities with variable differing outcomes have been described in the literature, no consensus has been reached regarding the standard treatment. The purpose of this study was to evaluate the outcome of a minimally invasive technique that uses a ceramic hydroxyapatite cannulated pin (HA pin) for the treatment of SBCs.Between 1998 and 2015, we have treated 75 patients with SBCs either with continuous decompression by inserting HA pins after curettage and multiple drilling (group 1, n = 39 patients) or with calcium phosphate cement (CPC) filling after curettage (group 2, n = 36 patients). These patients were retrospectively analyzed for recurrence-free survival (RFS) and factors implicated in SBC recurrence.Seventy-five patients (50 man and 25 females) with a mean age of 17.5 ±â€Š11.6 years and a histopathologically confirmed diagnosis of SBCs were included. The mean follow-up period was 33 ±â€Š25.3 months. RFS were 88% at 1 year and 81% at 5 years. Residual or progressing cysts were observed in 12 patients after the surgery and 10 of them underwent additional surgery. Recurrence rate was significantly higher in patients under the age of 10 years (P = .01), in long bone cysts (P = .01), and in active phase cysts (P = .003) (log-rank test). Multivariate analysis results revealed that age less than 10 years was an independent risk factor of recurrence (P = .04). No significant difference in recurrence rate was observed between groups 1 and 2. However, the mean operating time was significantly shorter in group 1. (62.4 ±â€Š25.6 vs 110.5 ±â€Š48.4 minutes in group 2).Continuous decompression using HA pin is a less invasive surgical technique for the treatment of SBCs compared with CPC filling and has a high healing rate. The relapse rate was still high when the cysts were caused in children aged less than 10 years, located in the long bone, or remained adjacent to the epiphysis. LEVEL OF EVIDENCE: Level 3, Retrospective comparative study.