Novel method to create a bespoke cement spacer for use in the management of segmental long-bone defects.
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ABSTRACT:
SUBMITTER: Silk Z
PROVIDER: S-EPMC6667952 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.
| S-EPMC9953456 | biostudies-literature
Project description:In this study, a two-part bone tissue engineering scaffold was investigated. The scaffold consists of a solid poly(propylene fumarate) (PPF) intramedullary rod for mechanical support surrounded by a porous PPF sleeve for osseointegration and delivery of poly(dl-lactic-co-glycolic acid) (PLGA) microspheres with adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). Scaffolds were implanted into critical size rat segmental femoral defects with internal fixation for 12 weeks. Bone formation was assessed throughout the study via radiography, and following euthanasia, via microcomputed tomography and histology. Mechanical stabilization was evaluated further via torsional testing. Experimental implant groups included the PPF rod alone and the rod with a porous PPF sleeve containing PLGA microspheres with 0, 2 or 8 ?g of rhBMP-2 adsorbed onto their surface. Results showed that presence of the scaffold increased mechanical stabilization of the defect, as evidenced by the increased torsional stiffness of the femurs by the presence of a rod compared to the empty defect. Although the presence of a rod decreased bone formation, the presence of a sleeve combined with a low or high dose of rhBMP-2 increased the torsional stiffness to 2.06 ± 0.63 and 1.68 ± 0.56 N·mm, respectively, from 0.56 ± 0.24 N·mm for the rod alone. The results indicate that, while scaffolds may provide structural support to regenerating tissues and increase their mechanical properties, the presence of scaffolds within defects may hinder overall bone formation if they interfere with cellular processes.
| S-EPMC3163689 | biostudies-literature
Project description:The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which received either bovine collagen carrier with 200 mug rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls at weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time.
| S-EPMC2772904 | biostudies-literature
Project description:Local or systemic stem cell delivery has the potential to promote repair of a variety of damaged or degenerated tissues. Although various stem cell sources have been investigated for bone repair, few comparative reports exist, and cellular distribution and viability postimplantation remain key issues. In this study, we quantified the ability of tissue-engineered constructs containing either human fetal or adult stem cells to enhance functional repair of nude rat critically sized femoral defects. After 12 weeks, defects treated with cell-seeded polymer scaffolds had significantly higher bone ingrowth and torsional strength compared to those receiving acellular scaffolds, although there were no significant differences between the cell sources. Next, stem cells were labeled with fluorescent quantum dots (QDs) in an attempt to noninvasively track their distribution after delivery on scaffolds. Clear fluorescence was observed at implantation sites throughout the study; however, beginning 7-10 days after surgery, signals were also observed at contralateral sites treated with acellular QD-free scaffolds. Although immunostaining for human nuclei revealed retention of some cells at the implantation site, no human cells were detected in the control limb defects. Additional histological analysis of implantation and control defect tissues revealed macrophages containing endocytosed QDs. Furthermore, QD-labeling appeared to diminish transplanted cell function resulting in reduced healing responses. In summary, augmentation of polymeric scaffolds with stem cells derived from fetal and adult tissues significantly enhanced healing of large segmental bone defects; however, QD labeling of stem cells eliminated the observed therapeutic effect and failed to conclusively track stem cell location long-term in vivo.
| S-EPMC2840521 | biostudies-literature
Project description:Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.
| S-EPMC8480893 | biostudies-literature
Project description:Antibiotic loaded bone cements are widely used in total joint replacement (TJR); despite many limitations such as a burst release which leads to antibiotic concentration below inhibitory levels and possibly contributing to the selection of antibiotic resistant strains. In order to address such limitations and to simultaneously address antibiotic resistance and short-term antimicrobial activity, we developed a nanocomposite bone cement capable of providing a controlled release of antimicrobial agents from bone cement to act as prophylaxis or treatment against prosthetic joint infections (PJIs). Gentamicin and chlorhexidine were loaded in combination on silica nanoparticles surface using layer-by-layer coating technique (LbL) combining hydrolysable and non-hydrolysable polymers. The drug release from the nanocomposite continued for >50 days at concentrations higher than the commercial formulation containing the same amount of antimicrobial drugs, where burst release for few days were observed. Moreover, the nanocomposite bone cement showed superior antimicrobial inhibition without adversely affecting the mechanical properties or the ability of osteoblasts to grow. In vivo experiments with an infected bone lesion model along with mass-spectrometric analysis also provided further evidence of efficacy and safety of the implanted nanocomposite material as well as its prolonged drug eluting profile. The developed nanocomposite bone cement has the potential to reduce PJIs and enable treatment of resistant established infections; moreover, the newly developed LbL based nano-delivery system may also have wider applications in reducing the threat posed by antimicrobial resistance.
| S-EPMC10824671 | biostudies-literature
Project description:Spontaneous bone regeneration could occur to reestablish mandibular bony continuity in patients who underwent partial or total mandibulectomy for tumors with periosteum-preserving. However, scarce data is available related to the precise role of periosteum in this bone regeneration. Therefore we aimed to investigate the gene expression of periosteum that were involved in the mandibular bone regeneration. Mandibular segmental defects were created in six mini-pigs with periosteum preserved. The periosteum of defects and control site were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the mechanisms concerning immature wound healing were clearly up-regulated at week 1. In contrast, by week-2, the GO categories of skeletal development, ossification and bone mineralization were significantly over-represented at week-2 with several genes encoding cell differentiation, extracellular matrix formation, and anatomical structure development. Furthermore, Tgfβ/Bmp, Wnt and Notch signaling were all related to the osteogenic process in this study. Besides osteogenesis, genes related to angiogenesis and neurogenesis were also prominent at week-2. These findings revealed that the gene expression profile of the periosteum's cells participating in bone regeneration varied in different time points, and numbers of candidate genes that differentially expressed during early healing stages of intramembranous bone regeneration were suggested.
| S-EPMC5648814 | biostudies-literature
Project description:ObjectivesIn recent years, the increase in utilisation of bone substitutes in the reconstruction of bone defects has been fuelled by donor site complications associated with autologous bone harvesting. However the ability of bone substitute to stimulate bone union while maintaining fracture reduction has been a topic of debate. Cerament Bone Void Filler (CBVF) is a novel biphasic and injectable ceramic bone substitute that has high compressive strength and the ability to promote cancellous bone healing.Materials and methodThis is a retrospective study to evaluate the surgical outcome of utilising CBVF in the treatment of depressed metaphyseal bone fractures over a two year period. The patients were followed up for at least six months after surgery and clinical parameters such as wound site complications were collated. Radiographic imaging was evaluated to determine loss of fracture reduction and rate of cement resorption.ResultsThirteen patients with depressed metaphyseal fractures were enrolled, which included: (i) one proximal humerus fracture; (ii) three tibial plateau fractures; and (iii) nine calcaneal fractures. None of the patients showed significant collapse in fracture reduction after six months of follow up. Cement resorption was noted in one patient as early as three weeks after surgery. There were no cases of cement leak or wound site complications.ConclusionCerament Bone Void Filler (CBVF) is a promising bone graft substitute in the management of depressed metaphyseal bone fractures, with the ability to maintain fracture reduction despite cement resorption.
| S-EPMC6611836 | biostudies-literature
Project description:IntroductionThe traditional clinical treatment of long segmental bone defects usually requires multiple operations and depends on donor availability. The 3D bio-printing technology constitutes a great potential therapeutic tool for such an injury. However, in situ 3D bio-printing remains a major challenge.ObjectivesIn this study, we report the repair of long segmental bone defects by in situ 3D bio-printing using a robotic manipulator 3D printer in a swine model.MethodsWe systematically optimized bio-ink gelation under physiological conditions to achieve desirable mechanical properties suitable for bone regeneration, and a D-H kinematic model was used to improve printing accuracy to 0.5 mm.ResultsThese technical improvements allowed the repair of long segmental defects generated on the right tibia of pigs using 3D bio-printing within 12 min. The 3D bio-printing group showed improved treatment effects after 3 months.ConclusionThese findings indicated that robotic in situ 3D bio-printing is promising for direct clinical application.
| S-EPMC8132211 | biostudies-literature
Project description:BackgroundSegmental bone transport is a common technique for treating large segmental bone defects. However, a docking site procedure is often necessary in segmental bone transport. To date, no prognostic factors for the need of docking site procedure have been reported. Thus, the decision is often made at random, based on the surgeon's subjective judgment and experience. The aim of this study was to identify prognostic factors for the need of docking site operation.MethodsPatients with segmental bone transport in lower extremity bone defects were included regardless of age, aetiology, and defect size. We excluded patients undergoing treatments that were not yet completed, and those who discontinued therapy by any reason. The need for docking site operation was modelled with logistical and linear regression as well as univariate analysis of variances (ANOVA). Receiver operating characteristics (ROC) curve analysis was also performed.ResultsTwenty-seven patients from age 12 to 74 years (mean age: 39.07 ± 18.20 years) were included. The mean defect size was 76.39 ± 41.10 mm. The duration of transport (days) showed a significant influence (p = 0.049, 95%CI: 1.00-1.02) on the need for docking site operation. No other significant influences were detected.ConclusionA link between the duration of transport and the need for docking site operation was detected. Our data showed that if a threshold of about 188 days is exceeded, docking surgery should be considered.
| S-EPMC10276496 | biostudies-literature