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.     

Actions of osteoporosis treatments on bone histomorphometric remodeling: a two-fold principal component analysis

Summary

This was the first study to apply principal component analysis method to bone histomorphometric parameters. The results corroborated teriparatide’s distinct, yet different, mechanisms of action, which stimulate both bone formation and resorption.

Introduction

This study consolidated bone histomorphometric parameters and compared the effects of two osteoporosis treatments on bone remodeling by using a principal component analysis (PCA).

Methods

Included in this analysis were postmenopausal women with osteoporosis who were treated with either teriparatide or alendronate and who completed transiliac bone biopsy at either 6 or 18 months in the randomized, double-blind Forteo Alendronate Comparator Trial. Eighteen histomorphometric parameters were grouped into formation and resorption categories. The first principal component of each category was estimated through the PCA. The summation of principal formation component (PFC) and principal resorption component (PRC) was calculated to represent the overall level of bone turnover. The difference between PFC and PRC was computed to determine the balance between formation and resorption.

Results

The PFC was significantly higher in the teriparatide group than in the alendronate group (P?<?0.0001), while the PRC was numerically lower in the alendronate group (P?=?0.18). The mean difference between the PFC and PRC was positive in the teriparatide group and negative in the alendronate group.

Conclusions

Our approach of consolidating bone histomorphometric remodeling parameters corroborated the idea that the distinct, yet different, mechanisms of action of teriparatide treatment stimulate both bone formation and resorption, and alendronate treatment suppresses both bone formation and resorption.     

Die M.-abductor-digiti-minimi-Lappenplastik zur Defektdeckung im Handbereich

Objective

Defect coverage of the ulnar aspect of the hand, wrist and hypothenar with an abductor digiti minimi muscle flap and split skin graft.

Indications

Soft tissue defects of the ulnar aspect of the hand, wrist and hypothenar. Osteomyelitis of the fifth metacarpal bone.

Contraindications

Large defects >?3?×?5 cm, complex hand trauma, injuries of the ulnar artery or within the area of the pedicle.

Surgical technique

Marking of the flap’s rotational radius, using the pisiform bone as the center point. Ulnar skin incision and exposure and detachment of the distal flap pole, which is located at the level of the metacarpophalangeal (MCP) joint. Dissection of the abductor digiti minimi muscle flap up to the vascular pedicle in the area of the pisiform bone. Transposition and fixation of the flap onto the defect after opening of the tourniquet. Coverage of the muscle flap with a split skin graft. Wound closure of the donor side.

Postoperative management

Palmar cast splinting in intrinsic-plus position for 10 days physiotherapy. Scar care and compression glove for 3 months.

Results

In total, 9 patients showed good results with a reliable defect coverage due to a constant anatomy and easy preparation.     

Handgelenksarthrodese mit gef??gestieltem Fibulasegment bei handgelenksnahen Unterarmtumoren

Objective

Total tumor resection and defect resconstruction by vascularized fibula graft and total wrist fusion.

Indications

Primary extended bone tumors of the distal radius.

Contraindications

Tumor infiltration of the whole carpus or of the neurovascular structures.

Surgical technique

En bloc resection of the tumor including the biopsy scar. Raising of a microvascular fibula graft including the peroneal vessels. Defect reconstruction using the fibula and stabilization of the total wrist fusion with a locking compression plate (LCP).

Postoperative management

Functional therapy of the fingers is possible, below elbow cast for 6 weeks. Weight bearing after 12 weeks according to bone healing.

Results

The operation technique described for preservation of the extremity in primary extended bone tumors of the distal radius was performed in our clinic in 2?patients since 2009. Tumor-free and pain-free hand function was found at the 2.5-year follow-up examinations. The patients had free range of motion of the fingers and preserved sensorimotor function. The MSTS (Musculoskeletal Tumour Society) scores by Enneking were 80% and 70%.     

Corticocancellous olecranon autograft for metacarpal defect reconstruction: a case report

Background

High-energy injuries to the hand frequently lead to bone defects as well as soft tissue loss. Early bone grafting of defects is well established in the literature; however, few options are available for autologous corticocancellous grafts. Most frequently cited studies describe the iliac crest or the distal radius donor sites.

Methods

In this case report, we describe a new technique of obtaining corticocancellous bone graft from the olecranon.

Results

Complete union of the segmental defect was achieved with this technique.

Conclusions

The olecranon donor site is outside the zone of injury and therefore safe to access, but within the upper extremity, thus avoiding the need for harvest from a distant site such as the iliac crest or the distal femur. Additional benefits of this site are the greater volume of graft that can be harvested compared to the distal radius as well as a more optimal ratio of cancellous to cortical graft available, compared to the iliac crest where the graft may be excessively cortical in nature.     

Radiologischer Vergleich zweier Verfahren zur ventralen Spondylodese

Background

The objective of this study was the radiological evaluation of osseous integration of autologous iliac crest graft and bovine bone graft after spondylodesis based on a standardized score.

Material and methods

Spondylodesis was performed on 18 sheep, divided into 2 groups, 1 with an autologous iliac crest graft and the other with a bovine bone graft. Computed tomography was performed 12 and 24 weeks postoperatively. The osseous integration was assessed by the Tübinger Score.

Results

The evaluation of the CT scans demonstrated a significantly better osseous integration of the autologous iliac crest graft compared to the bovine bone graft.

Conclusions

Based on our results, the bovine bone graft as a transplant for spondylodesis is inadvisable.     

A new strategy to enhance artificial ligament graft osseointegration in the bone tunnel using hydroxypropylcellulose

Purpose

The aim of this study was to determine whether hydroxypropylcellulose (HPC) coating of polyethylene terephthalate (PET) artificial ligaments enhances graft osseointegration in the bone tunnel.

Methods

Thirty New Zealand white rabbits underwent artificial ligament graft transplantation in the bilateral proximal tibia tunnels. One limb was implanted with an HPC-coated PET graft, and the contralateral limb was implanted with a non-HPC-coated PET graft as a control. The rabbits were then randomly sacrificed at weeks four and eight after surgery for biomechanical testing, histological examination, and histomorphometric and real-time polymerase chain reaction analysis.

Results

At week four after surgery, there were no statistically significant differences in the load to failure or stiffness values between the experimental and control limbs (P = 0.328 and P = 0.128, respectively). At week eight after surgery, the mean load to failure and stiffness value of the experimental limbs was higher than that of the control limbs (P < 0.001 and P = 0.018, respectively). At week eight after surgery, some protruding new bone tissue from the host bone to the graft was found in the HPC-coated group, while a thick fibrous tissue band was observed at the interface between the graft and the host bone in the control group. Histomorphometric analysis showed that the graft-bone interface width in the HPC-coated group was significantly narrower than that in the control group at week eight after surgery (P < 0.001). At weeks four and eight after surgery, the mRNA expression level of bone morphogenetic protein-2 in the HPC group was higher than that in the control group (P = 0.001 and P = 0.010, respectively). The mRNA expression level of osteopontin in the HPC group was higher than that in the control group only at week four after surgery (P = 0.032).

Conclusions

Our data show that an HPC coating on the surface of PET artificial ligament grafts may induce artificial ligament graft osseointegration in the bone tunnel.     

Arthroskopische Auff��llung von fehlplatzierten und erweiterten Bohrkan?len mit Beckenkammspongiosa bei Rezidivinstabilit?t nach Ersatzplastik des vorderen Kreuzbandes

Objective

Arhroscopically performed autologous bone grafting of the femoral or tibial tunnel after anterior cruciate ligament (ACL) reconstruction in symptomatic anterior knee instability.

Indications

Subjective and objective instability in cases with recurrent instability following ACL reconstruction with tibial or femoral tunnel malplacement and tunnel widening.

Contraindications

Open growth plates, severe osteoarthritic changes.

Surgical technique

Arthroscopic ACL graft resection and implant removal followed by debridement of the tunnel and the sclerotic tunnel walls. Cortical bone cylinders and cancellous bone grafts are harvested from the iliac crest and transplanted into the enlarged and malplaced tunnels. The harvest site may be filled with bone substitutes.

Results

Arthroscopic filling of malplaced or enlarged bone tunnels was performed in 42?patients (14?men, 28?women, age range 18?C37?years) with recurrent instability after ACL reconstruction. All patients presented with tunnel malplacement, while 38?patients also had tunnel widening. In 39?cases, a tibial bone graft was necessary; in 12?cases the femoral defect was filled with autologous bone. No complications, such as hematomas of infections, were observed. CT scans showed complete integration of the osseous grafts after 3?C6?months.     

A systematic review of comparative studies on bone graft alternatives for common spine fusion procedures

Background

The increased prevalence of spinal fusion surgery has created an industry focus on bone graft alternatives. While autologous bone graft remains the gold standard, the complications and morbidity from harvesting autologous bone drives the search for reliable and safe bone graft substitutes. With the recent information about the adverse events related to bone morhogenetic protein use, it is appropriate to review the literature about the numerous products that are not solely bone morphogenetic protein.

Purpose

The purpose of this literature review is to determine the recommendations for use of non-bone morphogenetic protein bone graft alternatives in the most common spine procedures based on a quantifiable grading system.

Study design

Systematic literature review.

Methods

A literature search of MEDLINE (1946–2012), CINAHL (1937–2012), and the Cochrane Central Register of Controlled Trials (1940–April 2012) was performed, and this was supplemented by a hand search. The studies were then evaluated based on the Guyatt criteria for quality of the research to determine the strength of the recommendation.

Results

In this review, more than one hundred various studies on the ability of bone graft substitutes to create solid fusions and good patient outcomes are detailed.

Conclusion

The recommendations for use of bone graft substitutes and bone graft extenders are based on the strength of the studies and given a grade.     

The Exeter method—acetabular impaction grafting with cemented reimplantation

Objective

Restoration of acetabular anatomy and biomechanics at revision hip surgery by replacing deficient acetabular bone through impaction of allograft and/or autograft bone chips.

Indications

Aseptic loosening of the socket due to osteolysis, bone loss from infection, iatrogenic bone loss due to implant removal, and in the primary setting protrusio acetabuli, dysplasia and previous acetabular fracture.

Contraindications

Large segmental peripheral acetabular defects which cannot be contained, the presence of untreated infection, unstable acetabular fractures, previous radiotherapy to the affected hip area.

Surgical technique

Sound exposure of the acetabulum with delineation of the bony defect. Creation of a host environment suitable for bone graft and containment of segmental defects using rim mesh or porous augments. Impaction grafting using layered allograft or autograft bone chips of 0.8–1 cm³, packed using hemispherical impactors, followed by cementing of a polyethylene acetabular component with pressurisation.

Postoperative management

Partial weight bearing 6 weeks, modified depending on level of containment and intra-operative findings.

Results

A successful and reproducible technique with survival up to 87?% at 20 years for aseptic loosening in the revision setting.     

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.     

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.     

Technique for methyl methacrylate cranioplasty to optimize cosmetic outcome

Background

Cranioplasty aims to reconstruct skull defects from fractures, decompressive craniectomies, tumors, and congenital anomalies in a cosmetically acceptable manner. We present a technique in methyl methacrylate cranioplasty that gives excellent cosmetic results by maintaining patient’s calvarial curvature.

Method

Cranioplasty material is placed into a plastic bag and packed inside the defect. Wire mesh cut larger than the defect is held in position to take the exact skull curvature. Once solid, the implant is fixed in position using titanium plates and mini-screws.

Conclusion

This is a simple, inexpensive method of achieving the most cosmetically desired cranioplasty results.     

Analysis of the factors affecting graft infection after cranioplasty

Background

The predictors of graft infection after cranioplasty (GIC) following decompressive craniectomy are not well established. Knowledge of the risk factors for GIC will allow development of preventive measures designed to reduce infection rates. Therefore, the objective of this study was to identify risk factors for the development of GIC.

Methods

A total of 85 patients underwent reconstructive cranioplasty after decompressive craniectomy between January 2009 and July 2011 and had a follow-up period of > 1 year; charts were reviewed retrospectively. Although autograft was used whenever possible, artificial bone was used for cranioplasty. GIC was defined as infection requiring removal of the bone graft.

Results

GIC occurred in six patients (7.05 %). GIC was not related to the indications for craniectomy, the interval of cranioplasty, graft material, or the size of the bone defect (p?=?0.433, p?=?0.206, p?=?0.665, and p?=?0.999, respectively). The GIC rate was significantly related to previous temporalis muscle resection, preoperative subgaleal fluid collection, operative times > 120 min, and postoperative wound disruptions (p?=?0.001, p?<?0.001, p?=?0.035, and p?=?0.016, respectively). Multiple logistic regression showed that the presence of a subgaleal fluid collection before cranioplasty significantly increased the risk of GIC (OR: 38.53; 95 % CI: 2.77–535.6; p?=?0.006).

Conclusions

The results of this study suggest that long operative times (> 120 min), craniectomy with temporalis muscle resection, the presence of preoperative subgaleal fluid collection, and postoperative wound disruption may be risk factors for graft infection after cranioplasty. Surgical techniques should be developed to reduce operative time and to avoid temporalis muscle resection when possible. In addition, meticulous dural closure aimed at reducing the formation of subgaleal fluid collection is important for the prevention of graft infections after cranioplasty.     

Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis or rheumatoid arthritis

Background

Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP.

Methods

CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3.

Results

CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA.

Conclusion

These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.     

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.     

Adipose-derived stem cells and rabbit bone regeneration: histomorphometric, immunohistochemical and mechanical characterization

Background

In the last few years, several attempts have been made to treat large bone loss, including the use of tissue engineering with osteoinductive scaffolds and cells. This study highlights the role of mesenchymal stem cells from adipose tissue (ASCs; adipose-derived stem cells) in a rabbit bone regeneration model.

Methods

We compared the neoformed bone tissues achieved by treating critical tibial defects with either hydroxyapatite alone (HA, group I) or hydroxyapatite–autologous ASC constructs (ASCs-HA, group II), investigating their histomorphometric, immunohistochemical and biomechanical properties.

Results

After eight weeks of follow-up, we observed advanced maturation and a spatial distribution of new bone that was more homogeneous in the inner parts of the pores in group II, not just along the walls (as seen in group I). The new tissue expressed osteogenic markers, and biomechanical tests suggested that the newly formed bone in group II had a higher mineral content than that in group I. Although variability in differentiation was observed among the different cell populations in vitro, no differences in bone healing were observed in vivo; the variability seen in vitro was probably due to local microenvironment effects.

Conclusions

Tibial defects treated with rabbit ASCs-HA showed an improved healing process when compared to the process that occurred when only the scaffold was used. We suggest that implanted ASCs ameliorate the bone reparative process either directly or by recruiting resident progenitor cells.     

Lower osteocalcin and osteopontin contents of the femoral head in hip fracture patients than osteoarthritis patients

Summary

In patients with femoral neck fracture, clinical factors, bone metabolism markers (in serum, urine, and bone), bone mineral density, radiographic parameters, and bone histomorphometric parameters were investigated to detect determinants of fragility fracture. The osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratio of cortical bone were selected as significant predictors.

Introduction

Measurement of bone mineral density is widely used to assess bone strength, but this also depends on other bone components and on bone structure. The objective of this study was to investigate risk factors for fracture related to bone quality, the patient??s history, and the patient??s lifestyle.

Methods

Twenty-one patients with femoral neck fracture and 18 patients with osteoarthritis were enrolled. Blood and urine samples were collected on admission to hospital, and bone samples were obtained from femoral necks resected during surgery. Multivariate logistic regression analysis was performed using osteoarthritis and femoral neck fracture as combined variables to assess the influence of alcohol or coffee intake, eating natto (fermented soybeans), osteocalcin and calcium concentrations, the osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratios of cortical bone and cancellous bone, various bone histomorphometric parameters, the bone mineral density of the lumbar spine and the intact contralateral femoral neck, and various radiographic parameters of the spine

Results

By forward stepwise multivariate analysis, the osteocalcin/deoxypyridinoline and osteopontin/calcium ratios of cortical bone were selected as significant factors for fracture (the odds ratios were 0.493 and <0.001, respectively; both P?<?0.001).

Conclusions

A decrease of osteopontin and osteocalcin in bone is important for promoting vulnerability to hip fracture.