Nonunion Defects Research Articles

A rhPDGF-BB/bovine type I collagen/β-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/β-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4or 8weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

DECIPHERING CELL–CELL INTERACTIONS OF HUMAN BONE MARROW MONONUCLEAR CELLS IN 3D CULTURE TO ENHANCE THE REGENERATIVE POTENTIAL OF BONE MARROW AUTOGRAFTS

Autografts containing bone marrow (BM) are current gold standard in the treatment of critical size bone defects, delayed union and bone nonunion defects. Although reaching unprecedented healing rates in bone reconstruction, the mode of action and cell-cell interactions of bone marrow mononuclear cell (BM-MNC) populations have not yet been described. BM-MNCs consist of a heterogeneous mixture of hematopoetic and non-hematopoetic lineage fractions. Cell culture in a 3D environment is necessary to reflect on the complex mix of these adherend and non-adherend cells in a physiologically relevant context. Therefore, the main aim of this approach was to establish conditions for a stable 3D BM-MNC culture to assess cellular responses on fracture healing strategies.BM samples were obtained from residual material after surgery with positive ethical vote and informed consent of the patients. BM-MNCs were isolated by density gradient centrifugation, and cellular composition was determined by flow cytometry to obtain unbiased data sets on contained cell populations. Collagen from rat tail and human fibrin was used to facilitate a 3D culture environment for the BM-MNCs over a period of three days. Effects on cellular composition that could improve the regenerative potential of BM-MNCs within the BM autograft were assessed using flow cytometry. Cell-cell-interactions were visualized using confocal microscopy over a period of 24 hours. Cell localization and interaction partners were characterized using immunofluorescence labeled paraffin sectioning.Main BM-MNC populations like Monocytes, Macrophages, T cells and endothelial progenitor cells were determined and could be conserved in 3D culture over a period of three days. The 3D cultures will be further treated with already clinically available reagents that lead to effects even within a short-term exposure to stimulate angiogenic, osteogenic or immunomodulatory properties. These measures will help to ease the translation from “bench to bedside” into an intraoperative protocol in the end.

Non-vascularised corticocancellous (tricortical) iliac bone graft longer than 3 cm for non-union after failed surgical treatment

We hypothesised that traditional iliac tricortical bone grafts (no vascularised) still have a reasonable role in promoting satisfactory bony healing in non-union defects of certain sizes. Here, we report the clinical/radiological outcomes through a retrospective case series. We screened 74 patients with definitive non-union in the long bones of the upper extremities who visited the outpatient department from 2008 to 2018. Among these patients, 25 who met our inclusion/exclusion criteria were investigated. The mean age was 51.92 years, and there were 12, 9, 1, and 3 lesions of the radius, ulna, clavicle, and humerus, respectively. The tools for primary fixations were plate and intramedullary nails in 24 and 1 patients, respectively. Six patients presented with atrophic non-union. The mean period from a previous surgery was 6.84 months. The mean defective bone sizes were 1.81 and 3.50cm pre-debridement and post-debridement, respectively. All devices had locking plates longer than the previous plate, and the graft was concurrently fixed by screws in three patients. At a mean of 15.92 weeks after the revision surgery, all patients experienced union. At the final follow-up, the clinical outcomes were satisfactory. No significant differences in clinical outcomes were found according to the lesion, type of non-union, period from the previous surgery, or harvest length of the iliac bone. If the proper indications and some technical aspects are considered, a non-vascularised iliac bone graft longer than 3cm could still be a reasonable option for treating diaphyseal non-union of the upper extremities. Level IV, retrospective case series.

TREATMENT OF VERY LARGE TRAUMATIC BONE DEFECTS WITH A BIODEGRADABLE POLYCAPROLACTONE-TRICALCIUM PHOSPHATE 3D-PRINTED SCAFFOLD: A REVIEW OF THREE CLINICAL CASES

The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting, but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient friendly option, especially in case of a concomitant infection.Multiple types of scaffolds for the Masquelet procedure (MP) are available, however these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remains high. This paper describes three infected tibial defect nonunions with a segmental defect over ten centimeters long treated with a customized 3D printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts.Three male patients, between the age of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than ten centimeters (range 11–15cm). First stage MPs consisted of extensive debridement, external fixation and placement of anterior lateral thigh flaps (ALT). Positive cultures were obtained from all patients during this first stage, that were treated with specific systemic antibiotics during 12 weeks. The second stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure a custom 3D printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA derived autograft, iFactor and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT-scans 6 months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight-bearing.This case report shows that 3D printed PCL-TCP cages in combination with biological adjuncts is a novel addition to the surgical treatment of very large bone defects in (infected) posttraumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication.

Review: cellularity in bone marrow autografts for bone and fracture healing.

The use of autografts, as primary cell and tissue source, is the current gold standard approach to treat critical size bone defects and nonunion defects. The unique mixture of the autografts, containing bony compartments and bone marrow (BM), delivers promising results. Although BM mesenchymal stromal cells (BM-MSCs) still represent a major target for various healing approaches in current preclinical research and respective clinical trials, their occurrence in the human BM is typically low. In vitro expansion of this cell type is regulatory challenging as well as time and cost intensive. Compared with marginal percentages of resident BM-MSCs in BM, BM mononuclear cells (BM-MNCs) contained in BM aspirates, concentrates, and bone autografts represent a readily available abundant cell source, applicable within hours during surgical procedures without the need for time-consuming and regulatory challenging cell expansion. This benefit is one reason why autografting has become a clinical standard procedure. However, the exact anatomy and cellularity of BM-MNCs in humans, which is strongly correlated to their unique mode of action and wide application range remains to be elucidated. The aim of this review was to present an overview of the current knowledge on these specific cell types found in human BM, emphasize the contribution of BM-MNCs in bone healing, highlight donor site dependence, and discuss limitations in the current isolation and subsequent characterization procedures. Hereby, the most recent and relevant examples of human BM-MNC cell characterization, flow cytometric analyses, and findings are summarized, with a strong focus on bone therapy.

Sequential application of small molecule therapy enhances chondrogenesis and angiogenesis in murine segmental defect bone repair.

The increasing incidence of physiologic/pathologic conditions that impair the otherwise routine healing of endochondral bone fractures and the occurrence of severe bone injuries necessitate novel approaches to enhance clinically challenging bone fracture repair. To promote the healing of nonunion fractures, we tested an approach that used two small molecules to sequentially enhance cartilage development and conversion to the bone in the callus of a murine femoral segmental defect nonunion model of bone injury. Systemic injections of smoothened agonist 21k(SAG21k) were used to stimulate chondrogenesis through the activation of the sonic hedgehog (SHH) pathway early in bone repair, while injections of the prolyl hydroxylase domain (PHD)2 inhibitor, IOX2, were used to stimulate hypoxia signaling-mediated endochondral bone formation. The expression of SHH pathway genes and Phd2 target genes was increased in chondrocyte cell lines in response to SAG21k and IOX2 treatment, respectively. The segmental defect responded to sequential systemic administration of these small molecules with increased chondrocyte expression of PTCH1, GLI1, and SOX9 in response to SAG and increased expression of hypoxia-induced factor-1α and vascular endothelial growth factor-A in the defect tissues in response to IOX2. At 6 weeks postsurgery, the combined SAG-IOX2 therapy produced increased bone formation in the defect with the bony union over the injury.Clinical significance: This therapeutic approach was successful in promoting cartilage and bone formation within a critical-size segmental defect and established the utility of a sequential small molecule therapy for the enhancement of fracture callus development in clinically challenging bone injuries.

Management algorithm of external fixation in lower leg arterial injury for limb salvages

PurposeThe aim of this study is to investigate the outcome of these limb-threatening injuries through external fixation treatment and to discuss the case of patients’ functional recovery after external fixation.MethodsDemographics, surgical treatment and outcomes in 88 patients with lower leg arterial injuries treated by external fixation at two trauma centers from 2009 to 2018 were reviewed. The primary outcome was the rate of successful lower leg salvage, while secondary outcomes were complications and functional recovery.ResultsEighty-eight patients were identified and 80 patients (90 legs) maintained a successful lower leg salvage. The mean age was 32.7 ± 10.8 years, and 81.8% were male. The primary outcomes included the following complications: pin-tract infection (8 legs), pins loosening (4 pins), wound superficial infection (7 legs), deep infection developed osteomyelitis (3 legs), bone nonunion or bone defect (17 legs) and amputation (8 legs). The average healing time of fracture was 5.6 ± 4.3 months. The maintain of external fixation average time was 5.8 ± 3.6 months. The improvement of scores of the pain, function and quality of life in our follow-up was statistically significant.ConclusionFor the lower extremity fracture patients with vascular injuries, using external fixation correctly can improve clinical outcomes and produce the improvement of pain, function and the quality of life.Level of evidenceRetrospective cohort, level IV.

Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats

BackgroundDiabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study.ResultsThe osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway.ConclusionsNormal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.Graphical

Le tibia proximal avec un clou en place peut être un site donneur pour un prélèvement d’os spongieux

IntroductionA preexisting implant at the harvesting site might dissuade the surgeon from considering the site as available for bone harvesting. This study aimed to investigate the quantity of cancellous bone graft that can be harvested from a proximal tibia with an inserted nail and to report the clinical outcomes of this bone graft harvesting technique. HypothesisOur hypothesis was that a certain amount of cancellous bone graft could be harvested from a proximal tibia with an inserted nail without compromising the surrounding environment and outcome of nonunion treatment. Material and methodsBone grafting from an ipsilateral proximal tibia with an inserted nail was performed in 32 patients for treating defect nonunion. The amount of harvested bone was measured using three parameters (weight, height, and volume). The effects of the proximal locking screw position on the quantity and location of bone graft harvest were analyzed. Clinical outcomes were evaluated by assessing the radiologic healing of the bone graft site and by assessing the donor-site complications. ResultsThe mean bone defect volume in the nonunion site was 31.1±18.3 (range, 10.6–87.0) cm3. The mean quantity of harvested bone from proximal tibias with an inserted nail was 21.2g, height was 3.9cm, and volume was 26.3cm3. A positive correlation was found between the quantity of harvested bone and the level of the lateral oblique interlocking screw hole in the tibial nail. All grafted bone successfully consolidated in all cases at an average of 5.8 months postoperatively. However, joint penetration during bone harvesting occurred in one case. DiscussionThe bony defect, which measured about 14.3cm3 could be filled with cancellous bone from a PT with an existing IM nail, without additional bone graft requirements. Even if an intramedullary nail exists inside the proximal tibia, harvesting cancellous bone at this site can be a viable option without serious complications. Level of evidenceIV; retrospective descriptive study.

Proximal tibia with an inserted nail can be an available donor site for harvesting cancellous bone

IntroductionA pre-existing implant at the harvesting site might dissuade the surgeon from considering the site as available for bone harvesting. This study aimed to investigate the quantity of cancellous bone graft that can be harvested from a proximal tibia with an inserted nail and to report the clinical outcomes of this bone graft harvesting technique. HypothesisOur hypothesis was that a certain amount of cancellous bone graft could be harvested from a proximal tibia with an inserted nail without compromising the surrounding environment and outcome of nonunion treatment. Material and methodsBone grafting from an ipsilateral proximal tibia with an inserted nail was performed in 32 patients for treating defect nonunion. The amount of harvested bone was measured using three parameters (weight, height, and volume). The effects of the proximal locking screw position on the quantity and location of bone graft harvest were analyzed. Clinical outcomes were evaluated by assessing the radiologic healing of the bone graft site and by assessing the donor site complications. ResultsThe mean bone defect volume in the nonunion site was 31.1±18.3 (range, 10.6–87.0) cm3. The mean quantity of harvested bone from proximal tibias with an inserted nail was 21.2g, height was 3.9cm, and volume was 26.3 cm3. A positive correlation was found between the quantity of harvested bone and the level of the lateral oblique interlocking screw hole in the tibial nail. All grafted bone successfully consolidated in all cases at an average of 5.8 months postoperatively. However, joint penetration during bone harvesting occurred in one case. DiscussionThe bony defect, which measured about 14.3 cm3 could be filled with cancellous bone from a PT with an existing IM nail, without additional bone graft requirements. Even if an intramedullary nail exists inside the proximal tibia, harvesting cancellous bone at this site can be a viable option without serious complications. Level of evidenceIV; Retrospective descriptive study.

Effect of Anti-Infective Reconstituted Bone Xenograft Combined with External Fixator on Serum CRP and PCT Levels and Prognosis of Patients with Bone Infection after Lower Extremity Long Bone Trauma.

Bone infection is one of the common complications of orthopedic surgery. After bone trauma occurs in the human body, the infection of Staphylococcus aureus and Gram-negative bacteria into the fracture area can lead to double infection of the soft tissue and bone tissue at the fracture site, leading to a variety of complications, mostly in the lower extremities. Bone infection easily causes bone destruction, bone nonunion, and bone defect, seriously affecting the quality of life of patients. The traditional treatment method of bone infection is to control the infection first and then repair the bone graft, but this method has a long course, poor efficacy, and high disability rate. In this study, anti-infective reconstituted bone xenograft (ARBX) combined with external fixation was used to treat patients with posttraumatic bone infections of the long bones of the lower extremities, to explore its efficacy, and to analyze its effects on serum CRP, PCT levels, and prognosis. Our results showed that ARBX combined with the external fixator had a good effect on the treatment of patients with bone infection after lower extremity long bone trauma, which could effectively enhance the repair and functional recovery of the limb bone, significantly alleviate the infection degree of patients, reduce the inflammatory response of the body, and have a good prognosis.

A Porcine Model for Repair of Long Bone Non-Union Defects Using Three-Dimensionally Printed Scaffolds

A Porcine Model for Repair of Long Bone Non-Union Defects Using Three-Dimensionally Printed Scaffolds

ROLE OF DIFFERENT CRITERIA IN OUTCOME ANALYSIS OF MANAGEMENT OF GAP NON-UNION

Back ground and objectives Gap or Defect non-union is not uncommon in Orthopaedic practice. Management involves prolonged periods of tedious procedures and decision making. The endpoint of such management does not reveal itself as a well-defined point. Follow ups must include some analysable outcome which should have a standardised criteria-based endpoint. A well-aligned, painless, noninfected, and functional limb is the goal of treatment. The objective of this study is to understand the role of different criterion to understand whether the goal has been reached. Summary The study is designed as retrospective, prospective observational study. It is conducted in tertiary care hospital (MIOT Hospitals, Chennai). Initial evaluation of all cases were done by Maurizio Catagni’s Classification. Type of surgeries, time spent in hospital, union time were calculated. Patients were followed up for a period of 1year. Patients with average defect size of 6.29cm on an average underwent 4.47 procedures and for an overall time of 17.8 weeks with around 83.80 % of individuals were able to return to their preinjury activity level. Analysis of the outcome was done by ASAMI bone criteria, ASAMI functional criteria, Cattneo et al criteria and Karstrom-Olerud’s functional evaluation criteria for lower limbs at onset of treatment, 6 months and 1 year of treatment,

Bone-Targeting Liposome-Encapsulated Salvianic Acid A Improves Nonunion Healing Through the Regulation of HDAC3-Mediated Endochondral Ossification.

AimNonunion is a major complication in fracture repair and remains a challenge in orthopaedics and trauma surgery. In this study, we aimed to evaluate the effectiveness of treatment of nonunion with a large radial defect using a bone-targeting liposome-encapsulated salvianic acid A (SAA-BTL)-incorporated collagen sponge and further elucidate whether the effects were closely related to histone deacetylase 3 (HDAC 3)-mediated endochondral ossification in nonunion healing process.MethodsFifteen New Zealand female rabbits were randomly divided into three groups. Segmental radius critical size defects (15 mm) were created via surgery on both the forelimbs of the rabbits. The SAA-BTL/SAA/saline-incorporated collagen sponges were implanted into the defects in the three groups, respectively, for four weeks of treatment. X-ray imaging, micro-computed tomography (CT) analysis, histology, and immunofluorescence analysis (HDAC3, collagen II, VEGFA, and osteocalcin) were performed to determine the effects of the treatments. In addition, a short interfering RNA was applied to induce HDAC3 knockdown in the chondrogenic cell line ATDC5 to investigate the roles of HDAC3 and SAA intervention in endochondral ossification in nonunion healing.ResultsX-ray imaging and micro-CT results revealed that SAA-BTL-incorporated collagen sponges significantly stimulated bone formation in the nonunion defect rabbit model. Furthermore, immunofluorescence double staining and histology analysis confirmed that SAA-BTL significantly increased the expression of P-HDAC3, collagen II, RUNX2, VEGFA, and osteocalcin in vivo; accelerated endochondral ossification turnover from cartilage to bone; and promoted long bone healing of nonunion defects. ATDC5 cells knocked down for HDAC3 showed significantly decreased expression of HDAC3, which resulted in reduced expression of chondrogenesis, osteogenesis, and angiogenesis biomarker genes (Sox9, Col10a1, VEGFA, RUNX2, and Col1a1), and increased expression of extracellular matrix degradation marker (MMP13). SAA treatment reversed these effects in the HDAC3 knockdown cell model.ConclusionSAA-BTL can improve nonunion healing through the regulation of HDAC3-mediated endochondral ossification.

A novel technique of ulna strut grafting for post-septic radial clubhand deformity: Case series of 4 patients with review of literature

BackgroundThough distal end radius fractures are one of the commonest fractures to occur, their nonunions are extremely uncommon. Out of these, post-septic defect nonunions with acquired radial clubhand deformity are even more rare and pose unique problems in management. We present a case series of 4 patients of post-septic radius nonunion with acquired radial clubhand deformity successfully treated with a novel technique of using Ulna Strut grafting for radius defect after ulnar shortening. All 4 patients have a good functional and cosmetic outcomes with radiological union at the cost of minimal limb length discrepancy of the forearm. MethodsThis is a case series of 4 patients with a retrospective study design and study duration of 3 years from August 2016 till March 2019.4 patients presenting to us with post-septic defect nonunions of radius with an acquired radial clubhand deformity were selected with a mean age of 19.75 years which included 2 males and 2 females. ResultsThe mean time for radiological union was 3.125 months. The average range of motion at the wrist joint was 35° of flexion and 50° of extension with average protonation being 47.5° and supination being 75°.There were no subsequent complications reported in these patients except for a minimal limb length discrepancy with satisfactory functional outcomes in all the patients. ConclusionThe use of Ulnar shortening and Ulna strut grafting for the treatment of defect nonunions of radius with acquired clubhand deformity yielded predictable results. It is a simple procedure that does not require additional training, with no additional morbidity of iliac crest or fibula bone grafting and had a minimum complication rate. The technique looks promising in the future, though a study on a larger population would further strengthen the predictability of this unique technique.

Treatment strategies of defect nonunion with vascular damaged by induced membrane technique: Is two-stage treatment sufficient?

Introduction: Defect nonunion is often associated with vascular damaged, concomitant infection and unfavorable soft tissue. Although several procedures used for bone defect nonunion, recently the induced membrane (IM) technique has gained great popularity in the world. The aim of this article is to evaluate the efficacy of vascular damaged nonunions with treated IM technique.Patients and Methods: This retrospective study included tibial defect nonunions of twenty-four patients (22 men, 2 women) with treated IM technique, from January 2014 to December 2018. According to the angiography of the extremity, a decrease in blood flow or obstruction in arterial vessels was suggested as vascular damaged group (n = 11) (Group 1), without vascular damaged group (n = 13) (Group 2). All surgeries applied during IM technique treatment including start with cement insertion and until last control were defined as number of surgeries.Results: The average time to union (40.18 ± 10.01 weeks – 38.61 ± 11.20 weeks) and the mean defect size (6.54 ± 1.75 cm – 6.61 ± 1.85 cm), no statistical differences were found between 2 groups (p >0.05). The average of spacer use was 11.27 (6 to 16) and 7.23 (6 to 10) weeks in group 1and 2, respectively. The mean number of surgeries was 3.91 ± 0.83 (at least 3 and at most 5) in group 1 and 2.31 ± 0.48 (2 to 3) in group 2.Conclusion: Although nonunions with vascular damage may require more surgeries and duration to spacer, a similar time to union and union rate were achieved compared to without vascular damage.

Safety and efficacy of in vitro generated bone-like material for in vivo bone regeneration – a feasibility study

Bone-like viable tissue can be generated in vitro by utilizing a combination of inorganic matrix, osteoblasts, osteogenic media and application of adequate mechanical stimulation of the cells. To pursue the proof that the in vitro generated bone-like tissue (BLT) is capable of bridging a critical bone gap in vivo without adverse effects, the in vitro cytotoxicity method (MTT) and murine in vivo model were implemented, by implanting the BLT into calvaria critical bone gap in rats. The endpoints for the evaluation of this concept were histological and radiographic data which should show the effectiveness of this method. We found that there was no cytotoxic effect of the BLT according to the MTT assay and no carcinogenic or other morbid effects of the BLT in vivo (mice experiment, n = 10) The critical gaps in BLT -implanted animals (experimental model with rats) demonstrated full bridging of the calvaria critical bone gap with vascularized woven bone (n = 3) as opposed to animals treated with vehicle material (n = 3), which maintained an open gap without any visible closure, according to gross examination, X-ray imaging and histological analysis. The newly formed bone tissue was characterized by pronounced presence of bone marrow regions and newly formed host blood vessels, a strong indication for functional osseointegration. Therefore, the in vitro generated BLT, which causes bone regeneration in critical gaps, has the translational potential to bridge bone non-union defects, without harmful systemic or cytotoxic effects. These initial feasibility results indicate a high safety profile following in vivo implantation of BLT and its potential clinical ability to be used as autologous bone graft.

Status quo and difficulties in standardized treatment of infected nonunion of tibia

In recent years, infection and infected nonunion after surgical treatment of tibial fracture have gradually increased, which has brought tremendous psychological and economic burdens to patients. At present, awareness and attention in the field of traumatic bone infections is insufficient, and many experienced orthopedic surgeons lack the basic knowledge and formal training on management of traumatic bone infections. Tibial intramedullary nail infection and infectious bone defect nonunion are difficult to treat and have a high recurrence rate. This article reviews the special principles of bacterial biofilm formation, surface competition, Klemm three factors and bone infection typing in the treatment of bone infection, the reamed debridement of tibial intramedullary nail fixation infection, the application of local antibiotics and the comparison between bone transport and inducing membrane techniques in the treatment of infectious nonunion. This article aims to provide some help for orthopedic surgeons in the systematic treatment of tibial infection. Key words: Osteomyelitis; Tibial fractures; Fracture fixation, intramedullary; Infected nonunion

A Modification of Internal Bone Transport Method for Reconstruction of Nonunion of Forearm.

Background:Defects of bone and soft tissue occur frequently after high-energy trauma, infections, and tumor resection. Treatment options are limited and outcomes are controversial in nonunion. Classical reconstruction methods are challenging. We describe a method of internal bone transport for treatment of complicated nonunion of the forearm. This method permits axial and internal bone transport without harming the distorted and complex neurovascular anatomy or soft-tissue envelope.Materials and Methods:Five patients (mean age, 27 years) with defect nonunion (3 ulna, 2 radius) were treated. Mean preoperative defect size was 36 mm, mean shortening was 14 (0–30) mm, and the extent of surgical resection was 24 (20–40) mm. Total bone loss due to defect, resection, or shortening was 74 mm. According to Paley classification, two of the patients had B1, and three had B3 defect nonunion. This study treats defect nonunion of the forearm using an internal bone-transport method. Our method involved cannulated screws, a cerclage wire, and a circular fixator being used in combination. When transportation was completed, internal fixation of the docking site with a plate and screws was done, with bone grafting after fixator removal. Bone healing and functional outcomes were assessed with radiographs and disabilities of the arm, shoulder, and hand (DASH) scores, respectively.Results:Mean followup was 67.6 months. Solid osseous union and functional improvement were achieved in all cases. Mean bone loss was 66 mm, mean fixator time was 131.8 days, the lengthening index was 1.3 days/mm, and the fixator index was 2.1 days/mm. DASH score was 82.2 before treatment and 15.36 after treatment.Conclusions:Using our method, internal bone transport and progressive axial docking of defects can be done with minimal effects on surrounding neurovascular arrangements and soft tissues. Size of fixators can be decreased and formation of painful scar tissue can be avoided.

Mineralized Polysaccharide Transplantation Modules Supporting Human MSC Conversion into Osteogenic Cells and Osteoid Tissue in a Non-Union Defect.

Regenerative orthopedics needs significant devices to transplant human stem cells into damaged tissue and encourage automatic growth into replacements suitable for the human skeleton. Soft biomaterials have similarities in mechanical, structural and architectural properties to natural extracellular matrix (ECM), but often lack essential ECM molecules and signals. Here we engineer mineralized polysaccharide beads to transform MSCs into osteogenic cells and osteoid tissue for transplantation. Bone morphogenic proteins (BMP-2) and indispensable ECM proteins both directed differentiation inside alginate beads. Laminin and collagen IV basement membrane matrix proteins fixed and organized MSCs onto the alginate matrix, and BMP-2 drove differentiation, osteoid tissue self-assembly, and small-scale mineralization. Augmentation of alginate is necessary, and we showed that a few rationally selected small proteins from the basement membrane (BM) compartment of the ECM were sufficient to upregulate cell expression of Runx-2 and osteocalcin for osteoid formation, resulting in Alizarin red-positive mineral nodules. More significantly, nested BMP-2 and BM beads added to a non-union skull defect, self-generated osteoid expressing osteopontin (OPN) and osteocalcin (OCN) in a chain along the defect, at only four weeks, establishing a framework for complete regeneration expected in 6 and 12 weeks. Alginate beads are beneficial surgical devices for transplanting therapeutic cells in programmed (by the ECM components and alginate-chitosan properties) reaction environments ideal for promoting bone tissue.