The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis.Aims
Methods
Various approaches have been implemented to enhance bone regeneration, including the utilization of autologous platelet-rich plasma and bone morphogenetic protein-2. The objective of this study was to evaluate the impact of Marburg Bone Bank-derived bone grafts in conjunction with platelet-rich plasma (PRP), recombinant human bone morphogenetic protein-2 (rhBMP-2), and zoledronic acid (ZA) on osteogenesis within rabbit bone defects. Methodology. Bone defects (5mm in diameter) were created in the femurs of 96 male rabbits. The animals were allocated into five groups: (1) bone graft + PRP (BG + PRP), (2) bone graft + 5μg rhBMP-2 (BG + rhBMP-2), (3) bone graft + 5μg ZA (BG + ZA), (4) bone graft + 10μg rhBMP-2 + 5μg ZA (BG + rhBMP-2 + ZA), and (5) bone graft (BG). Marburg Bone Bank-processed human femoral head allografts were utilized for bone grafting. The rabbits were euthanized at 14-, 30-, and 60-days post-surgery, and their femurs underwent histopathological and histomorphometric assessments. Results. Histomorphometric analysis revealed significantly enhanced de novo osteogenesis within the bone allografts in the BG + PRP and BG + rhBMP-2 groups compared to the BG, BG + ZA, and BG + rhBMP-2 + ZA groups at 14 and 30 days (p < 0.05). However, on day 60, the BG + rhBMP-2 group exhibited elevated osteoclastic activity (early resorption). The local co-administration of ZA with thermally treated grafts impeded both bone graft resorption and new bone formation within the bone defect across all time points. The addition of ZA to BG + rhBMP-2 resulted in diminished osteogenic activity compared to the BG + rhBMP-2 group (p < 0.000). Conclusion. The study findings indicated that the combination of PRP and rhBMP-2 with Marburg bone grafts facilitates early-stage osteogenesis in bone
Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats. Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT. Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling. The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone
Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration. Materials and methods:. A 3D-printed biodegradable biomaterial containing calcium phosphate and aragonite (calcium carbonate) was fabricated using a Bioplotter. The physicochemical properties of the material were characterised. The materials were assessed in vitro for cytotoxicity and ostegenic potential and in vivo in rat intercondylar Φ3mm bone defect model for 3 months and Φ5mm of mini pig femoral bone defects for 6 months. The results showed that the materials contained hydroxyapatite and calcium carbonate, with the compression strength of 2.49± 0.2 MPa, pore size of 300.00 ± 41mm, and porosity of 40.±3%. The hydroxyapatite/aragonite was not cytotoxic and it promoted osteogenic differentiation of human umbilical cord matrix mesenchymal stem cells in vitro. After implantation, the bone
Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article:
Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model. A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.Aims
Methods
The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.Aims
Methods
Critical size bone defects pose a serious clinical problem, as the intrinsic healing capacity of bone fails due to the size of the
Objectives. Long bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done. Methods. We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses. Results. Comparable results were obtained with autologous BMA clot and ABG, except for the quantification of new bone by micro-CT. Significantly more bone was found in the ABG-treated ulnar defects than in those treated with autologous BMA clot. This is possibly due to the remnants of necrotic autograft fragments that persisted within the
Aim. Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1). Method. 163 patients were treated for osteomyelitis or infected fractures with a single-stage excision, implantation of antibiotic carrier, stabilisation and wound closure. All had Cierny & Mader Type III (n=128) or Type IV (n=35) infection. No bone grafting was performed in any patient. Patients were followed up for a minimum of 12 months (mean 21.4 months; 12–56). Bone void filling was assessed on serial digitised, standardized radiographs taken immediately after surgery, at 6 weeks, 3, 6 and 12 months and then yearly. Data on defect size, location, degree of void filling, quality of the bone-biomaterial interface and material leakage were collected. Bone formation was calculated at final follow-up, as a percentage of initial defect volume, by determining the bone area on AP and lateral radiographs to the nearest 5%. Results. 138 patients had adequate radiographs for assessment. Infection was eradicated in 95.7%. 2.5% of patients suffered a fracture during follow-up. Overall, bone formation was good (mean 73.8% defect filling), with one quarter of patients having complete defect filling and 87% having more than 50% of the
The retear of the rotator cuff (RC) repair is a significant problem. Usually it is the effect of poor quality of the tendon. The aim was to evaluate histologically two types of RC reconstruction with scaffold. We have chosen commercially available scaffold polycaprolactone based poly(urethane urea). Rat model of supraspinatus tendon injury was chosen. There were four study groups: RC tear (no repair) (n=10), RC repair (n=10), RC repair augmented with scaffold (n=10) and RC reconstruction with scaffold interposition between tendon and bone (n=10). The repairs were investigated histologically at 6 and 16 weeks. The results in two groups in which scaffold was used had significantly better scores at 6 weeks comparing to non-scaffold groups (16,4±3, 17,3± 2,8 vs. 12,5±4,4, 13,8±1,4 respectively) and 16 weeks (23±1,9, 22,8±1,6 vs. 13,8±3,3, 14,9± 3,8 respectively). Results in two scaffold groups improved between 6 and 16 weeks. Signs of foreign body reaction against scaffold were not observed. Application of scaffold to strengthen the repair site and bridging of the tendon
Bioactive functional scaffolds are essential for support of cell-based strategies to improve bone regeneration. Adipose-tissue-derived-stromal-cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential to replace BMSC for therapeutic stimulation of bone-defect healing. Their osteogenic potential is, however lower compared to BMSC, a deficit that may be overcome in growth factor-rich orthotopic bone defects with enhanced bone-conductive scaffolds. Objective of this study was to compare the therapeutic potency of human ASC and BMSC for bone regeneration on a novel nanoparticulate β-TCP/collagen-carrier (β-TNC). Cytotoxicity of β-TCP nanoparticles and multilineage differentiation of cells were characterized in vitro. Cell-seeded β-TNC versus cell-free controls were implanted into 4 mm calvarial bone-defects in immunodeficient mice and bone healing was quantified by µCT at 4 and 8 weeks. Tissue-quality and cell-origin were assessed by histology. β-TNC was non-toxic, radiolucent and biocompatible, lent excellent support for human cell persistence and allowed formation of human bone tissue by BMSC but not ASC. Opposite to BMSC, ASC-grafting significantly inhibited calvarial bone healing compared to controls. Bone formation progressed significantly from 4 to 8 weeks only in BMSC and controls yielding 5.6-fold more mineralized tissue in BMSC versus ASC-treated defects. Conclusively, β-TNC was simple to generate, biocompatible, osteoconductive, and stimulated osteogenicity of BMSC to enhance calvarial
Orbital floor (OF) fractures are commonly treated by implanting either bioinert titanium or polyethylene implants, or by autologous grafts. A personalized implant made of biodegradable and osteopromotive poly(trimethylene carbonate) loaded with hydroxyapatite (PTMC-HA) could be a suitable alternative for patients where a permanent implant could be detrimental. A workflow was developed from the implant production using stereolithography (SLA) based on patient CT scan to the implantation and assessment its performance (i.e. implant stability, orbit position, bone formation) compared to personalised titanium implants in a repair OF defect sheep model. Implants fabrication was done using SLA of photo-crosslinkable PTMC mixed with HA [1–3]. Preclinical study: (sheep n=12, ethic number 34_2016) was conducted by first scanning the OF bone of each sheep in order to design and to fabricate patient specific implants (PSI) made of PTMC-HA. The fabricated PSI was implanted after creating OF defect. Bone formation and
During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly
In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. Tissue engineering may be an alternative for cranial bone repair. Titanium (Ti) and its alloys are widely used in many clinical devices because of perfect biocompatibility, highly corrosion resistance and ideal physical properties. An important progress in treating bone defects has been the introduction of bone morphogenetic proteins (BMPs), specifically BMP-2. The proteins induce osteogenic cell differentiation in vitro, as well as bone
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone
The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.Objectives
Methods
Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the
Bone is capable of regeneration, and
We reviewed 34 consecutive patients (18 female-16 male) with
isthmic spondylolysis and grade I to II lumbosacral spondylolisthesis
who underwent in situ posterolateral arthodesis between the L5 transverse
processes and the sacral ala with the use of iliac crest autograft.
Ten patients had an associated scoliosis which required surgical correction
at a later stage only in two patients with idiopathic curves unrelated
to the spondylolisthesis. No patient underwent spinal decompression or instrumentation
placement. Mean surgical time was 1.5 hours (1 to 1.8) and intra-operative
blood loss 200 ml (150 to 340). There was one wound infection treated
with antibiotics but no other complication. Radiological assessment
included standing posteroanterior and lateral, Ferguson and lateral flexion/extension
views, as well as CT scans. Aims
Methods