Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

Clinical Efficacy of GBR Technique Combined with Temporary Bridgework-Guided Gingival Contouring in Treating Upper Anterior Tooth Loss with Labial Bone Defects

Objective:To investigate the clinical effect of the guided bone regeneration(GBR)technique combined with temporary bridgework-guided gingival contouring in treating upper anterior tooth loss with labial bone defects.Methods:From July 2023 to April 2024,80 patients with upper anterior tooth loss and labial bone defects were admitted to the hospital and selected as evaluation samples.They were divided into an observation group(n=40)and a control group(n=40)using a numerical table lottery scheme.The control group received treatment with the GBR technique,while the observation group received treatment with the GBR technique combined with temporary bridges to guide gingival contouring.The two groups were compared in terms of clinical red aesthetic scores(PES),labial alveolar bone density,labial bone wall thickness,gingival papillae,gingival margin levels,and patient satisfaction.Results:The PES scores of patients in the observation group were higher than those in the control group after surgery(P<0.05).The bone density of the labial alveolar bone and the thickness of the labial bone wall in the observation group were higher than those in the control group.The levels of gingival papillae and gingival margins were lower in the observation group after surgery(P<0.05).Additionally,patient satisfaction in the observation group was higher than in the control group(P<0.05).Conclusion:The GBR technique combined with temporary bridge-guided gingival contouring for treating upper anterior tooth loss with labial bone defects can improve the aesthetic effect of gingival soft tissue,increase alveolar bone density and the thickness of the labial bone wall,and enhance patient satisfaction.This approach is suitable for widespread application in healthcare institutions.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Masquelet technique in military practice:specificities and future directions for combat-related bone defect reconstruction

Because of its simplicity,reliability,and replicability,the Masquelet induced membrane technique(IMT)has become one of the preferred methods for critical bone defect reconstruction in extremities.Although it is now used worldwide,few studies have been published about IMT in military practice.Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury,early wound infection,and even delayed management in austere conditions.Based on our clinical expertise,recent research,and a literature analysis,this narrative review provides an overview of the IMT application to combat-related bone defects.It presents technical specificities and future developments aiming to optimize IMT outcomes,including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.

Ilizarov technique for treatment of a giant aneurysmal bone cyst at the distal femur:A case report

BACKGROUND Aneurysmal bone cyst(ABC)is a benign cystic of unknown etiology,characterized by multiple chambers and a high recurrence rate.Current treatment options include vascular embolization,surgical excision,curettage with cavity filling,sclerosing agent injection into the cavity,radiotherapy,and systemic drug therapy.Among these,surgical excision and curettage are the preferred treatment modalities.However,when the cyst reaches a large size,extensive removal of diseased tissue during surgery can hinder bone healing.In our department,we treated a case of a large ABC at the distal end of the femur in a child using the Ilizarov technique.The tumor was completely excised,and reconstruction was achieved through autologous femoral bone transfer.The follow-up at two years post-surgery indicated good results without tumor recurrence,and the growth and development of the child were essentially unaffected.CASE SUMMARY An 11-year-old boy was presented with an accidental fracture of his right leg.Despite having been examined at other hospitals,he had not received treatment.Given the potential for significant bone defects and the difficulty of the surgery,our doctors opted to use the Ilizarov technique to minimize harm to the patient.Upon admission,the patient underwent a needle biopsy and complete tumor resection-the Ilizarov technique assisted in the transport and reconstruction of the autologous femoral bone.Postoperatively,the patient exhibited regular followups,during which bone transport was gradually performed,and the external fixation frame was removed on time.Follow-up X-rays of the right lower limb displayed no tumor recurrence,with a normal appearance.Bone formation at the cutting site was satisfactory,and the union of the bone ends indicated good healing.After two years of follow-up,the patient had essentially returned to normal.CONCLUSION We successfully applied the Ilizarov technique to treat ABC,reducing the financial burden of patients and the pain of multiple surgeries.In cases where significant bone defects occur,the Ilizarov technique has demonstrated satisfactory therapeutic outcomes.

Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved

BACKGROUND Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in long bone defect and nonunion management along with free vascularized grafting and induced membrane technique. However, the shortcomings and problems of these methods still remain the issues which restrict their overall use.AIM To study the recent available literature on the role of Ilizarov non-free bone plasty in long bone defect and nonunion management, its problems and the solutions to these problems in order to achieve better treatment outcomes.METHODS Three databases(Pub Med, Scopus, and Web of Science) were searched for literature sources on distraction osteogenesis, free vascularized grafting and induced membrane technique used in long bone defect and nonunion treatment within a five-year period(2015-2019). Full-text clinical articles in the English language were selected for analysis only if they contained treatment results,complications and described large patient samples(not less than ten cases for congenital, post-tumor resection cases or rare conditions, and more than 20 cases for the rest). Case reports were excluded.RESULTS Fifty full-text articles and reviews on distraction osteogenesis were chosen.Thirty-five clinical studies containing large series of patients treated with this method and problems with its outcome were analyzed. It was found that distraction osteogenesis techniques provide treatment for segmental bone defects and nonunion of the lower extremity in many clinical situations, especially in complex problems. The Ilizarov techniques treat the triad of problems simultaneously(bone loss, soft-tissue loss and infection). Management of tibial defects mostly utilizes the Ilizarov circular fixator. Monolateral fixators are preferable in the femur. The use of a ring fixator is recommended in patients with an infected tibial bone gap of more than 6 cm. High rates of successful treatment were reported by the authors that ranged from 77% to 100% and depended on the pathology and the type of Ilizarov technique used. Hybrid fixation and autogenous grafting are the most applicable solutions to avoid after-frame regenerate fracture or deformity and docking site nonunion.CONCLUSION The role of Ilizarov non-free bone plasty has not lost its significance in the treatment of segmental bone defects despite the shortcomings and treatment problems encountered.

3D Printing Hip Prostheses Offer Accurate Reconstruction,Stable Fixation,and Functional Recovery for Revision Total Hip Arthroplasty with Complex Acetabular Bone Defect

Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing technology in the reconstruction of such acetabular bone defects.We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology.Reconstruction of bone defect by conventional methods was difficult in these patients.In this endeavor,we used radiographic methods,related computer software such as Materialise's interactive medical image control system and Siemens NX software,and actual surgical experience to estimate defect volume,prosthesis stability,and installation accuracy,respectively.Moreover,a Harris hip score was obtained to evaluate limb function.It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis,and its stability was reliable.The Harris hip score indicated a very good functional recovery in all three patients.In conclusion,3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA.It was able to achieve good curative effects in patients with large bone defects.

Management of Severe Femoral Bone Defect in Revision Total Hip Arthroplasty-A 236 Hip,6-14-year Follow-up Study

Summary： This study evaluated the clinical effect of impaction bone graft and distal press-fit fixation for the reconstruction of severe femoral bone defect in revision total hip arthroplasty. A total of 234 patients （involving 236 hips） with Paprosky III and 1V femoral bone defects were treated with the revision total hip arthroplasty from June 1998 to Aug. 2006. Impaction bone graft technique was used for 112 hips, with allogeneic freeze-dried bone as bone graft and SP II as prosthesis. With 124 hips, modular distal press-fit fixation and tapered femoral stem （MP stem） were employed. After the operation, the subjects were followed up on regular basis and results were assessed by using the Harris Hip Score （HHS） and 12-item Short Form Health Survey （SF-12）. Radiolucence, subsidence and loosening were observed and complications, including infection, fracture, dislocation etc. were recorded. A 6-14-year follow-up showed that prostheses failed, due to infection, in 4 patients of impaction bone graft group and that 6 patients in the press-fit fixation group experienced prosthesis failure, with the survival rates for the two techniques being 96.43% and 95.16%, respectively. One-way ANOVA showed that prosthesis survival was significantly associated with surgery-related complications （P〈0.05） and was not related to the type of the bone defects （P〉0.05）. The rate of complications bore significant association with the type of bone defects in the two groups （P〈0.05）. Our study showed that the two revision methods could achieve satisfactory mid-term and long-term results for the reconstruction of severe bone defects. It is of great significance for attaining high prosthesis survival rate to select suitable operation on the basis of the type of bone defect. Careful operative manipulation and post-operative rehabilitation aimed at reducing complications are also important.

Experimental study of natural hydroxyapatite/chitosan composite on reconstructing bone defects

Objective：To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods：We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. Operations were performed on the left tibias of 15 white rabbits to create two square bone defects. One of the defects was reconstructed with the composite, while the other was not repaired and used as a blank control. Three of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively and implants were evaluated anatomically and histologically. Results：No apparent rejection reaction was found, except for a mild inflammatory infiltration observed 2 weeks after surgery. Fibrous tissue became thinner 2 -8 weeks after surgery and bony connections were detected 12 weeks after surgery. The new bone was the same as the recipient bone by the 16th postoperative week. Conclusion：The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application.

ROLE OF TRANSFORMING GROWTH FACTOR β(TGF-β)IN REPAIRING OF BONE DEFECTS

TGF-β is a multifunctional cytokine that regulates many aspects of cellular function, including periosteal mesenchymal cell proliferation, differentiation. This experiment is to study its effects on bone defect repair. A rabbit radial bone defect model was used to evaluate the effect of TGF-β, which was extracted and purified from bovine blood platelets, on the healing of a large segmental osteoperiosteal defect. A 1. 5-centimeter segmental defect was created in the mid-upper part of the radial shaft of adult rabbits. The defect was filled with implant containing TGF-β that consisted of carrier and bovine TGF-β. Limbs served as controls received carrier alone. The defectswere examined radiographically and histologically at 4, 8,12 , 16 and 20 weeks after implantation. The results showed that in TGF-β implant group . the defect areas at 12 weeks post operation were bridged by uniform new bone and the cut ends of cortex could not be seen;while in control group, the defects remained clear. Only a small amount of new bone formed as a cap on the cut bone ends. In the experimental group, new lamellar and woven bone formed in continuity with the cut ends of the cortex. An early medullar canal appears to be forming and contained normal-appearancing marrow elements; while the control group displayed entirely fibrous tissue within the defect site. Remnants of the cancellous bone carrier were observed in the control specimen. These data demonstrate that exogenous TGF-β initiate osteogenesis and stimulate the bone defects repair in animal model.

Preparation of new tissue engineering bone-CPC/PLGA composite and its application in animal bone defects

To investigate the feasibility of implanting the biocomposite of calcium phosphate cement(CPC)/polylactic acid-polyglycolic acid(PLGA) into animals for bone defects repairing,the biocomposite of CPC/PLGA was prepared and its setting time,compressive strength,elastic modulus,pH values,phase composition of the samples,degradability and biocompatibility in vitro were tested.The above-mentioned composite implanted with bone marrow stromal cells was used to repair defects of the radius in rabbits.Osteogenesis was histomorphologically observed by using an electron-microscope.The results show that compared with the CPC,the physical and chemical properties of CPC/PLGA composite have some differences in which CPC/PLGA composite has better biological properties.The CPC/PLGA composite combined with seed cells is superior to the control in terms of the amount of new bones formed after CPC/PLGA composite is implanted into the rabbits,as well as the speed of repairing bone defects.The results suggest that the constructed CPC/PLGA composite basically meets the requirements of tissue engineering scaffold materials and that the CPC/PLGA composite implanted with bone marrow stromal cells may be a new artificial bone material for repairing bone defects because it can promote the growth of bone tissues.

Structural bone allografts with intramedullary vascularized fibular autografts for the treatment of massive bone defects in extremities

Objective:To report the clinical outcome of repairing massive bone defects biologically in limbs by homeochronous using structural bone allografts with intramedullary vascularized fibular autografts. Methods: From January 2001 to December 2005, large bone defects in 19 patients (11 men and 8 women, aged 6 to 35 years) were repaired by structural bone allografts with intramedullary vascularized fibular autografts in the homeochronous period. The range of the length of bone defects was 11 to 25 cm (mean 17.6 cm), length of vascularized free fibular was 15 to 29 cm (mean 19.2 cm), length of massive bone allografts was 11 to 24 cm (mean 17.1 cm). Location of massive bone defects was in humerus(n=1), in femur(n=9) and in tibia(n=9), respectively. Results: After 9 to 69 months (mean 38.2 months) follow-up, wounds of donor and recipient sites were healed inⅠstage, monitoring-flaps were alive, eject reaction of massive bone allografts were slight, no complications in donor limbs. Fifteen patients had the evidence of radiographic union 3 to 6 months after surgery, 3 cases united 8 months later, and the remained one case of malignant synovioma in distal femur recurred and amputated the leg 2.5 months, postoperatively. Five patients had been removed internal fixation, complete bone unions were found one year postoperatively. None of massive bone allografts were absorbed or collapsed at last follow-up. Conclusion: The homeochronous usage of structural bone allograft with an intramedullary vascularized fibular autograft can biologically obtain a structure with the immediate mechanical strength of the allograft, a potential result of revascularization through the vascularized fibula, and accelerate bone union not only between fibular autograft and the host but also between massive bone allograft and the host.

Biodegradable materials for bone defect repair

Compared with non-degradable materials,biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects,and have attracted extensive attention from researchers.In the treatment of bone defects,scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role,which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue.Traditional biodegradable materials include polymers,ceramics and metals,which have been used in bone defect repairing for many years.Although these materials have more or fewer shortcomings,they are still the cornerstone of our development of a new generation of degradable materials.With the rapid development of modern science and technology,in the 21 st century,more and more kinds of new biodegradable materials emerge in endlessly,such as new intelligent micro-nano materials and cell-based products.At the same time,there are many new fabrication technologies of improving biodegradable materials,such as modular fabrication,3 D and 4 D printing,interface reinforcement and nanotechnology.This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing,especially the newly emerging materials and their fabrication technology in recent years,and look forward to the future research direction,hoping to provide researchers in the field with some inspiration and reference.

Application of 3D-printed prosthesis in revision surgery with large inflammatory pseudotumour and extensive bone defect: A case report

BACKGROUND Hip revision surgery is the final treatment option for the failure of artificial hip joints, but it is more difficult than the initial operation. For patients with hip joint loosening around the prosthesis combined with large inflammatory pseudotumours and large segment bone defects, hip revision is even more difficult, and clinical reports are rare.CASE SUMMARY Male, 59 years old. The patient underwent left hip replacement 35 years ago and was now admitted to hospital due to massive masses in the left thigh, shortening of the left lower extremity, and pain and lameness of the left hip joint. X-ray, computed tomography and magnetic resonance imaging revealed prosthesis loosening, left acetabular bone defect(Parprosky IIIB type), and a bone defect of the left proximal femur(Parprosky IIIA type). Inflammatory pseudotumours were seen in the left hip and left thigh. Hip revision surgery was performed using a 3Dprinted custom acetabular prosthesis was used for hip revision surgery, which was produced by Arcam Electron Beam Melting system with Electron Beam Melting technology. The operation was successful, and the patient was followed up regularly after the operation. The custom-made acetabular prosthesis was well matched, the inflammatory pseudotumour was completely removed, the postoperative hip prosthesis was stable, and the old greater trochanter fracture was well reduced and fixed. The patient was partially weight-bearing with crutches 3 mo after the operation and walked with full weight-bearing after 6 mo. The hip prosthesis was stable, and there was no recurrence of inflammatory pseudotumours at the last follow-up. The Visual Analogue Scale was 3, and the Harris hip score was 90.CONCLUSION The use of 3D-printed personalized custom prostheses for complex hip revision surgery has satisfactory surgical results and has great clinical application value.

Modified membrane fixation technique in a severe continuous horizontal bone defect:A case report

BACKGROUND Continuous severe horizontal bone defect is common in the aesthetic maxillary anterior area,and presents a major challenge in implant dentistry and requires predictable bone augmentation to increase the width of the alveolar bone.CASE SUMMARY A 24-year-old man,with a history of well-controlled IgA nephropathy,presented to the Dentistry Department of our hospital complaining of missing his right maxillary anterior teeth 1 mo ago.Severe horizontal alveolar bone defects at sites of teeth 12,13 and 14 were diagnosed.A modified guided bone regeneration surgical approach stabilizing the absorbable collagen membrane and particulate graft materials by periosteal diagonal mattress suture(PDMS)combined with four corner pins was used for this severe continuous horizontal bone defect.The outcome revealed that the newly formed alveolar ridge dimension increased from 0.72 mm to 11.55 mm horizontally 10 mo postoperatively,with no adverse events.The implant surgery was successfully performed.CONCLUSION This case highlights that PDMS combined with four corner pins is feasible to maintain the space and stabilize the graft and membranes in severe continuous horizontal bone defect.

Autotransplantation of Teeth and the Reconstruction of Alveolar Bone Defects Using Artificial Bone: A Case Series

The aim of this study was to evaluate the outcome of autotransplantation or replantation of extracted teeth combining with reconstruction of alveolar bone defects in use of artificial bone grafting clinically and radiographically. This article presents a more useful and convenient method for repairing tooth and reconstruction of bone defecting with some interesting cases. Eleven patients (seven men and four women) in whom teeth with complete root formation were extracted and autotransplanted, the bone of receiving area was Insufficient. All transplanted teeth were stabilized with orthodontic wire and resin or 4-0 silk sutures;at the same time, artificial bone powder was filled. In 11 cases, the missing teeth were restored by autogenous teeth and the alveolar bone defect was restored by artificial bone, the improvement in the radiographic and clinical parameters strongly suggest that it may be a useful therapy to solve the problem of the missing teeth and alveolar bone insufficiency simultaneously. However, the risk of replacement root resorption remains.

Bone Regeneration Enhanced by Antigen-Extracted Xenogeneic Cancellous Bone Graft with rhBMP-2 in Rabbits Mandibular Defect Repair

The effects of large piece xenogeneic bone which was separated from healthy pigs as a scaffold on repair of mandibular defect was investigated and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with rhBMP-2 in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand Rabbits, and then randomly divided into 4 groups, which was grafted in the mandibular defects with AXCB, AXCB soaked with rhBMP-2, autograft bone, or blank. Equal number of animals from each group was classified into three time points (4, 8, and 12 weeks) after operation for gross pathological observation, hematoxylin and eosin (H & E) staining, radiographic examination, and bone density measurement. H & E staining revealed that the area percentage of bone regeneration in the group of AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 when at 4, 8, and 12 weeks, which was better than that of auto bone graft, prompting that the group of AXCB/rhBMP-2 graft had commendable osteogenic effect. And comparing with the AXCB without rhBMP-2, of which the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92, the osteogenic effect of AXCB/rhBMP-2 graft was demonstrated to be much better. In the group of AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We concluded that antigen-extracted xenogeneic cancellous bone (AXCB) graft soaked with rhBMP-2 had shown excellent osteogenic effect in repair of bone defects, with good biocompability.

Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo microcomputed tomographic and histologic e

The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.

Effects of low intensity pulsed ultrasound stimulation on bone regeneration in rat parietal bone defect model

Purpose: Low intensity pulsed ultrasound stimulation (LIPUS) has been clinically applied to promote bone fracture healing in the orthopedic field. Thus, it is likely that LIPUS also stimulates bone regeneration in bone defects in the cranial-maxillofacial area. However, this has not been clearly proved. Furthermore, optimal time point and period of the application after the surgery has not been reported. The purpose of the present study was to evaluate the effect of LIPUS on bone regeneration in the rat parietal bone defects especially focusing on time and period of the application. Materials and Methods: Eighteen Wistar rats (14 weeks old) were divided into 6 groups: 5 experimental groups and a control group. Bone defect of 5 mm diameter was prepared on each side of the parietal bone and customized gelatin membranes were placed over the bone defects. LIPUS (160 mW/cm2, 15 min/day) was applied to the defect area with an active transducer externally in the experimental groups according to the schedules of the applications: Group 1 (day 6 - 12), group 2 (day 13 - 19), group 3 (day 20 - 26), group 4 (day 6 - 19) and group 5 (day 6 - 26). All the animals were sacrificed at 28 days. The defects were analyzed with micro CT and then histologically. Results: In Group 1, new bone formation was significantly promoted and the newly-formed bone was thick and matured compared to the one of the control group. In other experimental groups there were tendencies of stimulation of new bone formation;however, they were not statistically significant. Discussion and Conclusion: The present study demonstrated that amount of new bone formation in the bone defect depended on the time and period of LIPUS application. It has been suggested that application of LIPUS at an early healing period, the second week after the surgery, effectively accelerated new bone formation.