This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
A local injection may be used as an early option in the treatment of Morton’s neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition. A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications.Aims
Methods
Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The
The October 2023 Foot & Ankle Roundup. 360. looks at: Risk factors for failure of total ankle arthroplasties; Effects of synovial fluid fracture haematoma to
Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.Aims
Methods
Objectives. Meniscal injuries are often associated with an active lifestyle. The damage of meniscal tissue puts young patients at higher risk of undergoing meniscal surgery and, therefore, at higher risk of osteoarthritis. In this study, we undertook proof-of-concept research to develop a cellularized human meniscus by using 3D bioprinting technology. Methods. A 3D model of bioengineered medial meniscus tissue was created, based on MRI scans of a human volunteer. The Digital Imaging and Communications in Medicine (DICOM) data from these MRI scans were processed using dedicated software, in order to obtain an STL model of the structure. The chosen 3D Discovery printing tool was a microvalve-based inkjet printhead. Primary mesenchymal stem cells (MSCs) were isolated from bone marrow and embedded in a collagen-based bio-ink before printing. LIVE/DEAD assay was performed on realized cell-laden constructs carrying MSCs in order to evaluate cell distribution and viability. Results. This study involved the realization of a human cell-laden collagen meniscus using 3D bioprinting. The meniscus prototype showed the biological potential of this technology to provide an anatomically shaped, patient-specific construct with viable cells on a biocompatible material. Conclusion. This paper reports the preliminary findings of the production of a custom-made, cell-laden, collagen-based human meniscus. The prototype described could act as the starting point for future developments of this collagen-based,
Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries. We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis.Objectives
Methods
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from
Objectives. The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of
Objectives. To compare the therapeutic potential of
To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed Objectives
Methods
Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft.Objectives
Methods
The major problem with repair of an articular cartilage injury
is the extensive difference in the structure and function of regenerated,
compared with normal cartilage. Our work investigates the feasibility
of repairing articular osteochondral defects in the canine knee
joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate
(ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells
(BMSCs) and assesses its biological compatibility. The bone–cartilage scaffold was prepared as a laminated composite,
using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer
of polylactic acid–hydroxyacetic acid as the bony scaffold, and
sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous
scaffold. Ten-to 12-month-old hybrid canines were randomly divided
into an experimental group and a control group. BMSCs were obtained
from the iliac crest of each animal, and only those of the third
generation were used in experiments. An articular osteochondral
defect was created in the right knee of dogs in both groups. Those
in the experimental group were treated by implanting the composites
consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs.
Those in the control group were left untreated.Objectives
Methods
Injury to the anterior cruciate ligament (ACL)
is one of the most devastating and frequent injuries of the knee. Surgical
reconstruction is the current standard of care for treatment of
ACL injuries in active patients. The widespread adoption of ACL
reconstruction over primary repair was based on early perception
of the limited healing capacity of the ACL. Although the majority
of ACL reconstruction surgeries successfully restore gross joint stability,
post-traumatic osteoarthritis is commonplace following these injuries,
even with ACL reconstruction. The development of new techniques
to limit the long-term clinical sequelae associated with ACL reconstruction
has been the main focus of research over the past decades. The improved
knowledge of healing, along with recent advances in tissue engineering
and regenerative medicine, has resulted in the discovery of novel
biologically augmented ACL-repair techniques that have satisfactory
outcomes in preclinical studies. This instructional review provides
a summary of the latest advances made in ACL repair. Cite this article:
The treatment of osteochondral lesions and osteoarthritis
remains an ongoing clinical challenge in orthopaedics. This review
examines the current research in the fields of cartilage regeneration,
osteochondral defect treatment, and biological joint resurfacing, and
reports on the results of clinical and pre-clinical studies. We
also report on novel treatment strategies and discuss their potential
promise or pitfalls. Current focus involves the use of a scaffold
providing mechanical support with the addition of chondrocytes or mesenchymal
stem cells (MSCs), or the use of cell homing to differentiate the
organism’s own endogenous cell sources into cartilage. This method
is usually performed with scaffolds that have been coated with a
chemotactic agent or with structures that support the sustained
release of growth factors or other chondroinductive agents. We also
discuss unique methods and designs for cell homing and scaffold
production, and improvements in biological joint resurfacing. There
have been a number of exciting new studies and techniques developed
that aim to repair or restore osteochondral lesions and to treat
larger defects or the entire articular surface. The concept of a
biological total joint replacement appears to have much potential. Cite this article:
The April 2013 Knee Roundup360 looks at: graft tension and outcome; chondrocytes at the midterm; pre-operative deformity and failure; the designer effect; whether chondroitin sulphate really does work; whether ACL reconstruction is really required; analgesia after TKR; and degenerative meniscus.
Matrix-assisted autologous chondrocyte transplantation (MACT)
has been developed and applied in the clinical practice in the last
decade to overcome most of the disadvantages of the first generation
procedures. The purpose of this systematic review is to document
and analyse the available literature on the results of MACT in the
treatment of chondral and osteochondral lesions of the knee. All studies published in English addressing MACT procedures were
identified, including those that fulfilled the following criteria:
1) level I-IV evidence, 2) measures of functional or clinical outcome,
3) outcome related to cartilage lesions of the knee cartilage.Objectives
Methods
The October 2012 Knee Roundup. 360. looks at: autologous chondrocytes and chondromalacia patellae; drilling the femoral tunnel at ACL reconstruction; whether we repair the radially torn lateral meniscus; factors associated with patellofemoral pain; mechanoreceptors and the allografted ACL; whether high tibial osteotomy can delay the need for knee replacement; return to sport after ACL reconstruction;
The August 2012 Knee Roundup360 looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy.
When transferring tissue regenerative strategies
involving skeletal stem cells to human application, consideration needs
to be given to factors that may affect the function of the cells
that are transferred. Local anaesthetics are frequently used during
surgical procedures, either administered directly into the operative
site or infiltrated subcutaneously around the wound. The aim of
this study was to investigate the effects of commonly used local anaesthetics
on the morphology, function and survival of human adult skeletal
stem cells. Cells from three patients who were undergoing elective hip replacement
were harvested and incubated for two hours with 1% lidocaine, 0.5%
levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability
was quantified using WST-1 and DNA assays. Viability and morphology
were further characterised using CellTracker Green/Ethidium Homodimer-1
immunocytochemistry and function was assessed by an alkaline phosphatase
assay. An additional group was cultured for a further seven days
to allow potential recovery of the cells after removal of the local
anaesthetic. A statistically significant and dose dependent reduction in cell
viability and number was observed in the cell cultures exposed to
all three local anaesthetics at concentrations of 25% and 50%, and
this was maintained even following culture for a further seven days. This study indicates that certain local anaesthetic agents in
widespread clinical use are deleterious to skeletal progenitor cells
when studied
Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting. There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.
In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.
This paper outlines the recent development of an exchange Travelling Fellowship scheme between the British and American Orthopaedic Research Societies.
Autologous chondrocyte implantation is an option in the treatment of full-thickness chondral or osteochondral injuries which are symptomatic. The goal of surgery and rehabilitation is the replacement of damaged cartilage with hyaline or hyaline-like cartilage, producing improved levels of function and preventing early osteoarthritis. The intermediate results have been promising in terms of functional and clinical improvement. Our aim was to explore the hypothesis that the histological quality of the repair tissue formed after autologous chondrocyte implantation improved with increasing time after implantation. In all, 248 patients who had undergone autologous chondrocyte implantation had biopsies taken of the repair tissue which then underwent histological grading. Statistical analysis suggested that with doubling of the time after implantation the likelihood of a favourable histological outcome was increased by more than fourfold (p <
0.001).
Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 ( The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.
Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.
Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 106 cells after three weeks’ tissue culture. Calcium sulphate (CaSO4) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO4 has not to our knowledge been reported in a clinical setting.
Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.
Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 107 AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 107 naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.
The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group. Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.
The treatment of osteochondral lesions of the talus has evolved with the development of improved imaging and arthroscopic techniques. However, the outcome of treatment for large cystic type-V lesions is poor, using conventional grafting, debridement or microfracture techniques. This retrospective study examined the outcomes of 50 patients with a cystic talar defect who were treated with arthroscopically harvested, cored osteochondral graft taken from the ipsilateral knee. Of the 50 patients, 45 (90%) had a mean good to excellent score of 80.3 (52 to 90) in the Karlsson-Peterson Ankle Score, at a mean follow-up of 36 months (24 to 83). A malleolar osteotomy for exposure was needed in 26 patients and there were no malleolar mal- or nonunions. One patient had symptoms at the donor site three months after surgery; these resolved after arthroscopic release of scar tissue. This technique is demanding with or without a malleolar osteotomy, but if properly performed has a high likelihood of success.
Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.
The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes
An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.
We have evaluated The results showed that the degree of bone formation was dependent on the properties of the graft material. The osteoconductive sintered matrix structure showed significant formation of bone at the implant-bone interface. The addition of autogenous marrow increased the penetration of new bone further into the central area of the matrix and also increased the degree of revascularisation. The osteoinductive growth factor BMP-7 induced penetration of new bone throughout the entire structure of the implant. The most effective treatment was with the combination of marrow cells and osteoinductive BMP-7.
The discrepancy between successful experimental studies of cartilage repair and the clinical results is unexplained. We have evaluated the effect of metabolic alterations in joint homeostasis owing to an articular defect on the outcome of cartilage repair using tissue engineering methods. We used 21 adolescent Dutch goats divided into three groups. The control knees were left untreated while the contralateral knee was randomised to receive either no treatment (N), early treatment (E) or late treatment (L). The metabolism of proteoglycans in the surrounding joint surface was determined and correlated with the O’Driscoll score used to quantify the histological aspect of the repair of the defect. Synthesis of proteoglycan (PG) was increased in all groups. The release of glucosaminoglycan (GAG) was significantly higher in the untreated but not after early transplantation (1.3 v 1.8 NS). The cartilage repair scores in the early treatment group were not as good as those of the normal control group, but were significantly better when compared with both the untreated defects and the late treated defects. Defects which had been treated late showed a significantly decreased score when compared with those which had had early treatment or the normal control group and did not differ (p = 0.12) from those with no treatment. The histological and biochemical scores closely resembled the macroscopic and functional parameters which showed a significant deterioration for the late treated group and those without treatment compared with animals treated early. Thus,
Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the
