Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

Background

Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of β-tricalcium phosphate (β-TCP) and collagen in repairing segmental bone defects.

Methods

Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of β-TCP granules and collagen, with or without 100 μg recombinant human HGF. Biweekly, bone regeneration and β-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests.

Results

Compared with the bone tissue treated with β-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of β-TCP were promoted 4 weeks postoperatively by treatment with HGF in the β-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the β-TCP granules were completed in a shorter period by combining HGF with β-TCP and collagen, compared with tissues without HGF.

Conclusions

The combined application of HGF in a β-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and β-TCP for treatment of bone defects made a substantial difference.     

Autologous platelet-rich plasma induces bone formation of tissue-engineered bone with bone marrow mesenchymal stem cells on beta-tricalcium phosphate ceramics

Background

The purpose of the study is to investigate whether autologous platelet-rich plasma (PRP) can serve as bone-inducing factors to provide osteoinduction and improve bone regeneration for tissue-engineered bones fabricated with bone marrow mesenchymal stem cells (MSCs) and beta-tricalcium phosphate (β-TCP) ceramics. The current study will give more insight into the contradictory osteogenic capacity of PRP.

Methods

The concentration of platelets, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-β1 (TGF-β1) were measured in PRP and whole blood. Tissue-engineered bones using MSCs on β-TCP scaffolds in combination with autologous PRP were fabricated (PRP group). Controls were established without the use of autologous PRP (non-PRP group). In vitro, the proliferation and osteogenic differentiation of MSCs on fabricated constructs from six rabbits were evaluated with MTT assay, alkaline phosphatase (ALP) activity, and osteocalcin (OC) content measurement after 1, 7, and 14 days of culture. For in vivo study, the segmental defects of radial diaphyses of 12 rabbits from each group were repaired by fabricated constructs. Bone-forming capacity of the implanted constructs was determined by radiographic and histological analysis at 4 and 8 weeks postoperatively.

Results

PRP produced significantly higher concentration of platelets, PDGF-AB, and TGF-β1 than whole blood. In vitro study, MTT assay demonstrated that the MSCs in the presence of autologous PRP exhibited excellent proliferation at each time point. The results of osteogenic capacity detection showed significantly higher levels of synthesis of ALP and OC by the MSCs in combination with autologous PRP after 7 and 14 days of culture. In vivo study, radiographic observation showed that the PRP group produced significantly higher score than the non-PRP group at each time point. For histological evaluation, significantly higher volume of regenerated bone was found in the PRP group when compared with the non-PRP group at each time point.

Conclusions

Our study findings support the osteogenic capacity of autologous PRP. The results indicate that the use of autologous PRP is a simple and effective way to provide osteoinduction and improve bone regeneration for tissue-engineered bone reconstruction.

     

The combination of mesenchymal stem cells and a bone scaffold in the treatment of vertebral body defects

Purpose

Vertebral body defects represent one of the most common orthopedic challenges. In order to advance the transfer of stem cell therapies into orthopedic clinical practice, we performed this study to evaluate the safety and efficacy of a composite bioartificial graft based on a hydroxyapatite bone scaffold (CEM-OSTETIC^®) combined with human mesenchymal stem cells (MSCs) in a rat model of vertebral body defects.

Methods

Under general isoflurane anesthesia, a defect in the body of the L₂ vertebra was prepared and left to heal spontaneously (group 1), implanted with scaffold material alone (group 2), or implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and histomorphometrical evaluation of the implant as well as micro-CT imaging of the vertebrae were performed.

Results

We observed a significant effect on the formation of new bone tissue in the defect in group 4 when compared to the other groups and a reduced inflammatory reaction in both groups receiving a scaffold and MSCs. We did not detect any substantial pathological changes or tumor formation after graft implantation.

Conclusions

MSCs in combination with a hydroxyapatite scaffold improved the repair of a model bone defect and might represent a safe and effective alternative in the treatment of vertebral bone defects.     

The use of beta-tricalcium phosphate and bone marrow aspirate as a bone graft substitute in posterior lumbar interbody fusion

Purpose

Due to the disadvantages of iliac crest bone and the poor bone quality of autograft gained from decompression surgery, alternative filling materials for posterior lumbar interbody fusion cages have been developed. β-Tricalcium phosphate is widely used in cages. However, data regarding the fusion rate of β-TCP assessed by computer tomography are currently not available.

Materials

A prospective clinical trial involving 34 patients (56.7 years) was performed: 26 patients were treated with single-level, five patients double-level and three patients triple-level PLIF filled with β-TCP and bone marrow aspirate perfusion, and additional posterior pedicle screw fixation. Fusion was assessed by CT and X-rays 1 year after surgery using a validated fusion scale published previously. Functional status was evaluated with the visual analogue scale and the Oswestry Disability Index before and 1 year after surgery.

Results

Forty-five levels in 34 patients were evaluated by CT and X-ray with a follow-up period of at least 1 year. Clinically, the average ODI and VAS for leg and back scores improved significantly (P < 0.001). CT assessment revealed solid fusion in 12 levels (26.67 %) and indeterminate fusion in 15 levels (34.09 %). Inadequate fusion (non-union) was detected in 17 levels (38.63 %).

Conclusion

The technique of PLIF using β-TCP yielded a good clinical outcome 1 year after surgery, however, a high rate of pseudoarthrosis was found in this series therefore, we do not recommend β-TCP as a bone graft substitute using the PLIF technique.     

Novel Microhydroxyapatite Particles in a Collagen Scaffold: A Bioactive Bone Void Filler?

Background

Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2.

Questions/purposes

Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2).

Methods

A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups.

Results

Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect.

Conclusions

The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns.

Clinical Relevance

The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects.     

Comparison of in vivo bioactivity and compressive strength of a novel superporous hydroxyapatite with beta-tricalcium phosphates

Introduction

Superporous hydroxyapatite (HAp-S) is a novel bone substitute that contains three-dimensionally interconnected macropores with micropores, which stimulate bone ingrowth into the material.

Method

We investigated the in vivo behaviour of HAp-S by comparing its bioactivity and biomechanical properties with beta-tricalcium phosphates (β-TCP). HAp-S or β-TCP was implanted in the lateral femoral condyle of rabbits. In vivo bioactivity of each material, including bone ingrowth and material resorption, was quantitatively evaluated by micro-CT and the ultimate compressive strength of the bone–material composite was also measured. Micro-CT showed that bone ingrowth in the HAp-S group significantly increased over time, while no significant increase was observed after 8?weeks in the β-TCP group.

Results

Although both materials showed gradual material resorption, β-TCP resorption was significantly greater than HAp-S. The ultimate compressive strength in the HAp-S group significantly increased over time up to six times its original value, while there was no significant increase in the β-TCP group. These results show that HAp-S resorption is concurrent with bone ingrowth, resulting in increasing compressive strength over 12?weeks. On the other hand, β-TCP resorption is fast but unaccompanied by bone ingrowth; consequently, it remains relatively fragile at least in the early period after implantation. Although these highly porous materials themselves are structurally and mechanically similar, there are significant differences in in vivo behaviour depending on the material composition.

Conclusion

These findings should be kept in mind when choosing the highly porous ceramics.     

Efficacy of two different demineralised bone matrix grafts to promote bone healing in a critical-size-defect: a radiological,histological and histomorphometric study in rat femurs

Purpose

The aim of the study was to compare two different demineralised bone matrices used clinically regarding their ability to induce bone healing in a critical-size-defect rat model.

Methods

We stabilised 4 mm femur defects with a custom-made plate and filled them either with demineralised bone matrix (DBM) or DBX (DBX Putty®). Bone morphogenetic protein 2 (BMP-2)-loaded collagen and an empty defect served as controls. The outcome was followed after 21 and 42 days by radiology (Faxitron; microCT) and histology.

Results

Defect healing did not occur in any animal from the empty control, DBM or DBX group. Residuals of the implanted material were still found after six weeks, but only limited callus formation was visible. In contrast, the BMP-2 control demonstrated enhanced formation of callus tissue and undisturbed healing. After 21 days, 11 out of 16 and after 42 days, 7 out of 8 BMP-2-treated animals showed complete defect bridging by cancellous bone tissue.

Conclusions

Demineralised bone grafts were not capable of defect reconstruction; only BMP-2 was able to provide sufficient stimulus to induce uneventful bridging under the specific experimental conditions.     

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

Background

Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue.

Materials and methods

One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO₂)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix.

Results

Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points.

Conclusions

This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.     

Oligo[poly(ethylene glycol)fumarate] Hydrogel Enhances Osteochondral Repair in Porcine Femoral Condyle Defects

Background

Management of osteochondritis dissecans remains a challenge. Use of oligo[poly(ethylene glycol)fumarate] (OPF) hydrogel scaffold alone has been reported in osteochondral defect repair in small animal models. However, preclinical evaluation of usage of this scaffold alone as a treatment strategy is limited.

Questions/purposes

We therefore (1) determined in vitro pore size and mechanical stiffness of freeze-dried and rehydrated freeze-dried OPF hydrogels, respectively; (2) assessed in vivo gross defect filling percentage and histologic findings in defects implanted with rehydrated freeze-dried hydrogels for 2 and 4 months in a porcine model; (3) analyzed highly magnified histologic sections for different types of cartilage repair tissues, subchondral bone, and scaffold; and (4) assessed neotissue filling percentage, cartilage phenotype, and Wakitani scores.

Methods

We measured pore size of freeze-dried OPF hydrogel scaffolds and mechanical stiffness of fresh and rehydrated forms. Twenty-four osteochondral defects from 12 eight-month-old micropigs were equally divided into scaffold and control (no scaffold) groups. Gross and histologic examination, one-way ANOVA, and one-way Mann-Whitney U test were performed at 2 and 4 months postoperatively.

Results

Pore sizes ranged from 20 to 433 μm in diameter. Rehydrated freeze-dried scaffolds had mechanical stiffness of 1 MPa. The scaffold itself increased percentage of neotissue filling at both 2 and 4 months to 58% and 54%, respectively, with hyaline cartilage making up 39% of neotissue at 4 months.

Conclusions

Rehydrated freeze-dried OPF hydrogel can enhance formation of hyaline-fibrocartilaginous mixed repair tissue of osteochondral defects in a porcine model.

Clinical Relevance

Rehydrated freeze-dried OPF hydrogel alone implanted into cartilage defects is insufficient to generate a homogeneously hyaline cartilage repair tissue, but its spacer effect can be enhanced by other tissue-regenerating mediators.     

Serum albumin enhances bone healing in a nonunion femoral defect model in rats: a computer tomography micromorphometry study

Purpose

Blood-derived proliferative factors such as platelet rich plasma or activated plasma are promising adjuvants for bone grafts. Our earlier studies showed that serum albumin itself can markedly enhance the proliferation of stem cells on bone allograft and postulated that albumin coating alone may improve bone graft integration in vivo.

Methods

Two femoral defect models were performed in adult male Wistar rats. In the critical size model a six millimetre gap was created in the midshaft of the femur and fixed with plate and screws, while a nonunion model was established by the interposition of a spacer in the osteotomy for four weeks which resulted in compromised healing and nonunion. Albumin coated and uncoated grafts were placed into the defects. Bone healing and morphometry were evaluated by μCT and histology four weeks after implantation of the grafts.

Results

In the critical size model none of the bone grafts were able to bridge the defect, and graft resorption was the typical outcome. In the nonunion model regular uncoated grafts had a low union rate (two out of six), which increased markedly when albumin coating was applied (six out of eight). Trabecular thickness and pattern factor improved significantly in the albumin coated group versus uncoated or empty controls.

Conclusions

Our results showed that serum albumin coating of bone grafts can enhance the remodelling and efficacy of treatment in a nonunion model.     

Papineau debridement,Ilizarov bone transport,and negative-pressure wound closure for septic bone defects of the tibia

Purpose

Ilizarov pioneered bone transport using a circular external fixator. Papineau described a staged technique for the treatment for infected pseudarthrosis of the long bones. This article presents a single-stage Papineau technique and Ilizarov bone transport, and postoperative negative-pressure wound dressing changes for septic bone defects of the tibia.

Materials and methods

We studied the files of seven patients (mean age, 32 years) with septic bone defects of the tibia treated with a Papineau technique and Ilizarov bone transport in a single stage, followed by postoperative negative-pressure wound dressing changes. All patients had septic pseudarthrosis and skin necrosis of the tibia. The technique included a single-stage extensive surgical debridement of necrotic bone, open bone grafting with cancellous bone autograft and bone transport, and postoperative negative-pressure wound dressing changes for wound closure. The mean time from the initial injury was 6 months (range, 4–8 months). The mean follow-up was 14 months (range, 10–17 months).

Results

All patients experienced successful wound healing at a mean of 29 days. Six patients experienced successful bone regeneration and union at the docking side at a mean of 6 months. One patient experienced delayed union at the docking site, which was treated with autologous cancellous bone grafting. Two patients experienced pin track infection, which was successfully treated with antibiotics and pin site dressing changes. All patients were able to return to their work and previous levels of activity, except one patient who had a stiff ankle joint and had to change his job. No patient experienced recurrence of infection, or fracture of the regenerated or transported bone segment until the period of this study.

Conclusion

The combined Papineau and Ilizarov bone transport technique with negative-pressure wound closure provides for successful eradication of the infection, reconstruction of the bone defect, and soft-tissue closure. A single-stage surgical treatment is feasible, without any complications.     

Arthroscopic three dimensional autologous chondrocyte transplantation with navigation-guided cartilage defect size assessment

Introduction

The treatment of large full thickness cartilage defects with matrix guided autologous chondrocyte transplantation shows promising results. However, in many cases an arthrotomy is needed to implant the cell seeded scaffolds. Recently techniques have been developed for arthroscopically guided ACT implantation. Correct defect mapping, to assess size and depth of the chondral lesions, and precise scaffold preparation and fixation are crucial for successful chondrocyte transplantation and remain to be not sufficiently optimized.

Method

In the present study, the geometries of two cartilage defects in cadaver knees were three times assessed, measured and transferred to biodegradable scaffolds with a navigation system by three different executors. The scaffolds were arthroscopically implanted into the cartilage defects.

Results

The cartilage defect assessment was reproducible between all executors for all defect geometries. The implanted scaffolds showed a correct defect filling.

Conclusion

The study showed the feasibility of an arthroscopic implantation of scaffolds for autologous chondrocytes transplantation. Navigation was a useful tool to exactly assess the cartilage defect geometry and allowed a precise transfer of navigated cartilage defect geometries for individualized scaffold preparation. Navigation can help to accomplish and optimize arthroscopically guided chondrocyte transplantations.     

Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction

Purpose

The aim of this study was to examine whether the addition of endothelial progenitor cells (EPCs) contributes to restoring the architectural and functional properties of newly formed bone for reconstruction of bone defects.

Methods

Bone marrow-derived EPCs and mesenchymal stem cells (MSCs) were co-seeded onto demineralized bone matrix (DBM) as a prevascularized tissue-engineered bone (TEB) for the repair of segmental bone defects to evaluate the effects of prevascularization of TEB on ameliorating morphological, haemodynamic and mechanical characteristics.

Results

The restoration of the intraosseous vasculature and medullary cavity was improved markedly compared to the non-prevascularized groups. The blood supply, biomechanical strength, and bone mineral density of the prevascularized group were significantly higher than those of the non-prevascularized groups during bone reconstruction.

Conclusions

The present study indicates that EPC-dependent prevascularization contributes to bone healing with structural reconstruction and functional recovery and may improve the understanding of correlation between angiogenesis and osteogenesis.     

Axially vascularized bone substitutes: a systematic review of literature and presentation of a novel model

Introduction

The creation of axially vascularized bone substitutes (AVBS) has been successfully demonstrated in several animal models. One prototypical indication is bone replacement in patients with previously irradiated defect sites, such as in the mandibular region. The downside of current clinical practice, when free fibular or scapular grafts are used, is the creation of significant donor site morbidity.

Methods

Based on our previous experiments, we extended the creation of an arterio-venous loop to generate vascularized bone substitutes to a new defect model in the goat mandibula. In this report, we review the literature regarding different models for axially vascularized bone substitutes and present a novel model demonstrating the feasibility of combining this model with synthetic porous scaffold materials and biological tissue adhesives to grow cells and tissue.

Results

We were able to show the principal possibility to generate axially vascularized bony substitutes in vivo in goat mandibular defects harnessing the regenerative capacity of the living organism and completely avoiding donor site morbidity.

Conclusion

From our findings, we conclude that this novel model may well offer new perspectives for orthopedic and traumatic bone defects that might benefit from the reduction of donor site morbidity.     

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Background

The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis.

Questions/purposes

We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing.

Methods

We soaked rhBMP-2/GM/CPC and rhBMP-2/CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology).

Results

The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation.

Conclusions

The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects.

Clinical Relevance

These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.     

The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

Summary

This study demonstrated an impaired biomaterial-mediated bone regeneration in a critical sized calvarial defect established within an ovariectomized rat model. Histological and microtomographic evidences were supported by an impaired osteoblastic gene expression and altered expression of estrogen receptors and adipogenic markers.

Introduction

This work aims to address the bone regeneration process in the ovariectomized rat model, by assessing a calvarial critical size defect implanted with a biocompatible bovine bone mineral graft.

Methods

Animals were randomly divided into two groups: Ovx (bilateral ovariectomy) and Sham (control surgery). Following 8 weeks, all animals were submitted to a surgical bicortical craniotomy (5-mm circular critical size defect), which was filled with a biocompatible mineral graft. Animals were euthanized at 1, 3, and 6 months following graft implantation (n?=?10), and results on the orthotopic bone regeneration process were blindly evaluated by radiographic, microtomographic, histological, histomorphometric, and gene expression techniques.

Results

In the attained model, in both Sham and Ovx groups, the bone regenerative process was found to occur in a slow-paced manner. Likewise, a qualitative evaluation of the microtomographic and histological analysis, as well as quantitative data from histomorphometric indexes, revealed reduced bone regeneration in Ovx animals, at the assayed time points. Significant differences were attained at the 3 and 6 months. Gene expression analysis revealed a reduced expression of osteoblastic-related genes and an altered expression of estrogen receptors and adipogenic markers, within the regenerating bone of Ovx animals.

Conclusions

Due to the similarities between the osteoporotic animal model and the human condition of postmenopausal osteoporosis, it might be relevant to consider the potential clinical implication of the osteoporotic condition in the biomaterial-mediated bone tissue healing/regeneration process.     

Novel use of cranial epidural space in rabbits as an animal model to investigate bone volume augmentation potential of different bone graft substitutes

Background

The success of bone augmentation to a major degree depends on the biomechanics and biological conditions of the surrounding tissues. Therefore, an animal model is needed providing anatomical sites with similar mechanical pressures for comparing its influence on different biomaterials for bone regeneration. The present report describes the new bone formation associated to biomaterial in a bursa created in the epidural space, between dura mater and cranial calvaria, under the constant pressure of cerebrospinal fluid.

Methods

Five adult California rabbits were used for the trial. In each animal, two bursae were created in the epidural spaces, in the anterior part of the skull, below both sides of the interfrontal suture. The spaces between dura mater and cranial calvaria were filled with in-situ hardening biphasic calcium phosphate containing hydroxyapatite and beta tricalcium-phosphate (BCP), in-situ hardening phase-pure beta-tricalcium phosphate (β-TCP) or without any biomaterials (sham). After 90 days, the animals were sacrificed, and the defect sites were extracted and processed for histomorphometric analysis by optical and backscattered electron microscopy.

Results

The cranial epidural spaces created (n?=?10) could be preserved by the application both BCP (n?=?3) and β-TCP biomaterials (n?=?3) in all experimental sites. The sites augmented with BCP showed less new bone formation but a trend to better volume preservation than the sites augmented with β-TCP. However, the bone in the BCP sites seemed to be more mature as indicated by the higher percentage of lamellar bone in the sites. In contrast, the created space could not be preserved, and new bone formation was scarce in the sham-operated sites (n?=?4).

Conclusion

The experimental bursae created bilaterally in the epidural space allows comparing objectively bone formation in relation to biomaterials for bone regeneration under permanent physiological forces from cerebrospinal fluid pressure.

     

No Effect of Hole Geometry in Microfracture for Talar Osteochondral Defects

Background

Débridement and bone marrow stimulation is an effective treatment option for patients with talar osteochondral defects. However, whether surgical factors affect the success of microfracture treatment of talar osteochondral defects is not well characterized.

Questions/purposes

We hypothesized (1) holes that reach deeper into the bone marrow-filled trabecular bone allow for more hyaline-like repair; and (2) a larger number of holes with a smaller diameter result in more solid integration of the repair tissue, less need for new bone formation, and higher fill of the defect.

Methods

Talar osteochondral defects that were 6 mm in diameter were drilled bilaterally in 16 goats (32 samples). In eight goats, one defect was treated by drilling six 0.45-mm diameter holes in the defect 2 mm deep; in the remaining eight goats, six 0.45-mm diameter holes were punctured to a depth of 4 mm. All contralateral defects were treated with three 1.1-mm diameter holes 3 mm deep, mimicking the clinical situation, as internal controls. After 24 weeks, histologic analyses were performed using Masson-Goldner/Safranin-O sections scored using a modified O’Driscoll histologic score (scale, 0–22) and analyzed for osteoid deposition. Before histology, repair tissue quality and defect fill were assessed by calculating the mean attenuation repair/healthy cartilage ratio on Equilibrium Partitioning of an Ionic Contrast agent (EPIC) micro-CT (μCT) scans. Differences were analyzed by paired comparison and Mann-Whitney U tests.

Results

Significant differences were not present between the 2-mm and 4-mm deep hole groups for the median O’Driscoll score (p = 0.31) and the median of the μCT attenuation repair/healthy cartilage ratios (p = 0.61), nor between the 0.45-mm diameter and the 1.1-mm diameter holes in defect fill (p = 0.33), osteoid (p = 0.89), or structural integrity (p = 0.80).

Conclusions

The results indicate that the geometry of microfracture holes does not influence cartilage healing in the caprine talus.

Clinical Relevance

Bone marrow stimulation technique does not appear to be improved by changing the depth or diameter of the holes.     

Revision total knee arthroplasty: experience with tantalum cones in severe bone loss

Background

Tantalum-made cones have been developed to compensate for large bone defect involving metaphyseal segment or major portion of the condyle or plateau during knee revision prosthetic surgery.

Materials and methods

We present our experience with femoral and tibial tantalum cones in 11 knees (12 cones overall were used, 6 on femur and 6 on tibia) with 2B or 3 Engh defect type during knee revision arthroplasty. Both cemented and cementless cones were used. Patients were submitted to a specific study protocol in order to exclude a new or persistent infection. Only one intra-operative complication not related to the implantation of the trabecular metal cone was observed.

Results

Neither early nor late post-operative re-infection was reported in our series at a mean follow-up of 39.8 months. Radiological analysis showed no cases of aseptic loosening or migration of the components. The only post-operative complication was delayed union of the tibial tuberosity in a patient who required osteotomy for surgical exposure. All patients improved both clinically and functionally.

Conclusions

The results of this study support the use of femoral and tibial porous tantalum metaphyseal cones as a viable option for revision knee arthroplasty with large amount of bone defects in both tibia and femur. We think that the main advantages of tantalum cones compared to structural bone graft lie in faster full weight-bearing recovery and in the cones' potential long-term maintenance of mechanical support. By our results, we can eventually exclude any concern regarding a possible direct correlation of the trabecular metal cones with re-infection.