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1.
Orthopade ; 48(4): 330-336, 2019 Apr.
Article in German | MEDLINE | ID: mdl-30758539

ABSTRACT

BACKGROUND: Fast track arthroplasty is becoming increasingly accepted in German-speaking countries. By optimizing treatment processes fast track programs promise faster recovery, increased patient satisfaction, quality improvement and reduction in the length of hospital stay. OBJECTIVES: The philosophy and treatment principles of fast track hip arthroplasty during the pre, intra and postoperative phase are described in the light of the current body of evidence. The challenges concerning fast track arthroplasty within the German health system are discussed. MATERIAL AND METHODS: Besides presenting our own data concerning a patient seminar and an opiate saving pain treatment, the most relevant literature related to fast track hip arthroplasty from a pubmed search is discussed. RESULTS: Fast track concepts can only be successfully implemented through close interdisciplinary team work. Preoperatively, a patient seminar can help to prepare patients better for surgery. Postoperatively, early mobilisation and pain treatment play a central role, whereat a clear reduction in opiate application can be achieved. CONCLUSION: Fast track hip arthroplasty makes rethinking with respect to traditional treatment principles necessary and demands a high degree of interdisciplinary team work. Particularly, as result of the specifics of the health system (DRG system and stationary rehabilitation), a nationwide establishment in Germany has not taken place so far.


Subject(s)
Arthroplasty, Replacement, Hip , Germany , Humans , Length of Stay , Patient Satisfaction
2.
Orthopade ; 47(9): 770-776, 2018 Sep.
Article in German | MEDLINE | ID: mdl-30143825

ABSTRACT

BACKGROUND: The application of cell- and growth factor-based techniques in conjunction with conventional surgical approaches has great therapeutic potential for the treatment of avascular necrosis of the femoral head (AVNFH). OBJECTIVES: This review provides an overview of new strategies for the treatment of AVNFH, with emphasis on cell and growth factor-based approaches. MATERIALS AND METHODS: The results of a literature search are summarised, the most relevant publications are presented and discussed by the authors. RESULTS: In the focus of new strategies for treatment of AVNFH are bone marrow-derived cell concentrates and ex vivo-expanded mesenchymal stem cells. Besides local application during core decompression, the systemic administration of cells via blood vessels supplying the femoral head is an interesting approach. The application of osteogenic and angiogenic growth factor-laden scaffold materials has also been clinically tested. Initial results of randomised clinical trials using cell- and growth factor-based approaches underline the potential of these innovative therapeutic strategies. Cell-based therapies are governed by EU law and generally require a manufacturing authorization. CONCLUSION: To date, only few randomized controlled clinical trials are available which additionally display a considerable diversity concerning cell parameters, cell processing, adjuvant surgical techniques and the quality outcome parameters. Therefore, a final statement about the effectiveness of new cell and growth factor-based strategies is currently not possible.


Subject(s)
Femur Head Necrosis , Cell- and Tissue-Based Therapy , Femur Head , Femur Head Necrosis/therapy , Humans , Intercellular Signaling Peptides and Proteins , Osteogenesis , Randomized Controlled Trials as Topic
3.
J Tissue Eng Regen Med ; 12(2): 494-504, 2018 02.
Article in English | MEDLINE | ID: mdl-28714574

ABSTRACT

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer-related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell-bone interactions. In this study, two established tissue-engineered bone constructs (TEBCs) were applied to a breast cancer-related metastasis model. A cylindrical medical-grade polycaprolactone-tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate-coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA-MB-231, SUM1315, and MDA-MB-231BO breast cancer cells were cultured in polyethylene glycol-based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer-related bone metastasis seen in patients.


Subject(s)
Bone Neoplasms/secondary , Bone and Bones/pathology , Breast Neoplasms/pathology , Models, Biological , Tissue Engineering/methods , Animals , Bone Neoplasms/pathology , Calcification, Physiologic/drug effects , Calcium Phosphates/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Female , Humans , Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology , Mice, SCID , Neoplasm Invasiveness , Organ Size/drug effects , Polyesters/pharmacology , Species Specificity , Tissue Scaffolds/chemistry , X-Ray Microtomography
4.
Orthopade ; 46(11): 947-953, 2017 Nov.
Article in German | MEDLINE | ID: mdl-28993845

ABSTRACT

BACKGROUND: Cell and growth factor based strategies bear great potential to support the healing processes in cartilage repair and the therapy of osteoarthritic joints. OBJECTIVES: The following review provides an overview of novel experimental strategies for the therapy of focal cartilage defects and osteoarthritis, with emphasis on cell and growth factor based approaches. MATERIALS AND METHODS: The authors summarize their own data regarding the intraarticular injection of stem cells to treat osteoarthritis of the knee and provide a synopsis of the available literature discussing the most significant publications. RESULTS: The development of novel strategies for the treatment of focal and arthrotic cartilage lesions focuses on the application of growth factors, platelet rich plasma (PRP), bone marrow (BMSAC) or adipose derived (stromal vascular fraction - SVF) cell concentrates, and ex vivo expanded mesenchymal stem cells (MSC). First clinical data on the use of expanded MSCs show the potential of this innovative therapeutic strategy. These approaches, however, are governed by EU law and often require approval by regulatory bodies. CONCLUSION: Currently, only a limited number of published, randomized, controlled trials available. Therefore, it is not possible to finally assess the efficacy of these strategies at this point in time.


Subject(s)
Cartilage, Articular/surgery , Osteoarthritis/surgery , Adipose Tissue/physiopathology , Bone Marrow/physiopathology , Cartilage, Articular/injuries , Cartilage, Articular/physiopathology , Humans , Intercellular Signaling Peptides and Proteins/therapeutic use , Mesenchymal Stem Cell Transplantation , Platelet-Rich Plasma/physiology
5.
J Tissue Eng Regen Med ; 11(7): 2081-2089, 2017 07.
Article in English | MEDLINE | ID: mdl-26648044

ABSTRACT

The properties of osteoblasts (OBs) isolated from the axial skeleton (tOBs) differ from OBs of the orofacial skeleton (mOBs) due to the different embryological origins of the bones. The aim of the study was to assess and compare the regenerative potential of allogenic bone marrow-derived mesenchymal progenitor cells with allogenic tOBs and allogenic mOBs in combination with a mPCL-TCP scaffold in critical-sized segmental bone defects in sheep tibiae. After 6 months, the tibiae were explanted and underwent biomechanical testing, micro-computed tomography (microCT) and histological and immunohistochemical analyses. Allogenic MPCs demonstrated a trend towards a better outcome in biomechanical testing and the mean values of newly formed bone. Biomechanical, microCT and histological analysis showed no significant differences in the bone regeneration potential of tOBs and mOBs in our in vitro study, as well as in the bone regeneration potential of different cell types in vivo. Copyright © 2015 John Wiley & Sons, Ltd.


Subject(s)
Bone Regeneration , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Osteoblasts , Tibia/injuries , Tibia/metabolism , Tissue Scaffolds , Allografts , Animals , Osteoblasts/metabolism , Osteoblasts/transplantation , Osteogenesis , Sheep , Tibia/diagnostic imaging , Tissue Engineering/methods , X-Ray Microtomography
6.
Orthopade ; 45(5): 425-32, 2016 May.
Article in German | MEDLINE | ID: mdl-27125234

ABSTRACT

BACKGROUND: Ruptures of the patellar tendon after total knee arthroplasty represent a rare but severe complication, which in general requires surgical therapy. OBJECTIVES: To implement a classification and correspondent therapy algorithm in consideration of the current literature for the treatment of patellar tendon ruptures after TKA. MATERIAL AND METHODS: A review of the recent literature and the author's experience are summarized in a classification and correspondent therapy algorithm for the treatment of patellar tendon ruptures after TKA. RESULTS: Ruptures of the patella tendon can be classified as avulsions (Type I), acute (Type II) and chronic ruptures (Type III). Avulsions are often of iatrogenic nature and can be sufficiently treated by transosseous refixation prior to implantation of the revision TKA. Acute ruptures of the patellar tendon can originate from trauma or intraoperative injury. The rupture can be restored by primary suture in combination with a wire cerclage in the case of good tendon quality and the absence of patient comorbidities (Type IIA). In the case of poor tendon quality or existing comorbidities (Type IIB) additional augmentation of the ruptured tendon, utilizing the autologous semitendinosus/gracilis tendon, is recommended. Chronic ruptures revealing a good patellar bone stock (Type IIIA) can be treated by a combination of a semitendinosus augmentation and a turndown quadriceps tendon flap. In the case of a poor patellar bone stock (Type IIIB) transpatellar fixation of the semitendinosus tendon is virtually impossible, so that an allograft augmentation or the use of a soft tissue muscle flap (i. e. the gastrocnemius flap) has to be considered. A failed complex reconstruction with or without infection (Type IIIC) is an invidious surgical task and needs to be addressed by the utilization of a muscle flap, an allograft or a patellectomy with or without arthrodesis.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Patella/injuries , Patella/surgery , Tendon Transfer/methods , Tenotomy/methods , Algorithms , Combined Modality Therapy/methods , Evidence-Based Medicine , Humans , Plastic Surgery Procedures/methods , Rupture/diagnostic imaging , Rupture/etiology , Rupture/therapy , Treatment Outcome
7.
Acta Biomater ; 23: 282-294, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26004222

ABSTRACT

Scaffold architecture guides bone formation. However, in critical-sized long bone defects additional BMP-mediated osteogenic stimulation is needed to form clinically relevant volumes of new bone. The hierarchical structure of bone determines its mechanical properties. Yet, the micro- and nanostructure of BMP-mediated fast-forming bone has not been compared with slower regenerating bone without BMP. We investigated the combined effects of scaffold architecture (physical cue) and BMP stimulation (biological cue) on bone regeneration. It was hypothesized that a structured scaffold directs tissue organization through structural guidance and load transfer, while BMP stimulation accelerates bone formation without altering the microstructure at different length scales. BMP-loaded medical grade polycaprolactone-tricalcium phosphate scaffolds were implanted in 30mm tibial defects in sheep. BMP-mediated bone formation after 3 and 12 months was compared with slower bone formation with a scaffold alone after 12 months. A multiscale analysis based on microcomputed tomography, histology, polarized light microscopy, backscattered electron microscopy, small angle X-ray scattering and nanoindentation was used to characterize bone volume, collagen fiber orientation, mineral particle thickness and orientation, and local mechanical properties. Despite different observed kinetics in bone formation, similar structural properties on a microscopic and sub-micron level seem to emerge in both BMP-treated and scaffold only groups. The guiding effect of the scaffold architecture is illustrated through structural differences in bone across different regions. In the vicinity of the scaffold increased tissue organization is observed at 3 months. Loading along the long bone axis transferred through the scaffold defines bone micro- and nanostructure after 12 months.


Subject(s)
Bone Morphogenetic Proteins/administration & dosage , Drug Implants/administration & dosage , Guided Tissue Regeneration/instrumentation , Tibial Fractures/therapy , Tissue Scaffolds , Animals , Bone Regeneration/drug effects , Combined Modality Therapy/methods , Equipment Failure Analysis , Fracture Healing/drug effects , Prosthesis Design , Radiography , Sheep , Tibial Fractures/diagnostic imaging , Tibial Fractures/pathology , Tissue Engineering/instrumentation , Treatment Outcome
8.
Gene ; 525(1): 99-106, 2013 Aug 01.
Article in English | MEDLINE | ID: mdl-23632238

ABSTRACT

Mandibular osteoblasts originate from the neural crest and deposit bone intramembranously, mesoderm derived tibial osteoblasts by endochondral mechanisms. Bone synthesized by both cell types is identical in structure, yet functional differences between the two cell types may exist. Thus, both matched juvenile and adult mandibular and tibial osteoblasts were studied regarding their proliferative capacity, their osteogenic potential and the expression of osteogenic and origin related marker genes. Juvenile tibial cells proliferated at the highest rate while juvenile mandibular cells exhibited higher ALP activity depositing more mineralized matrix. Expression of Hoxa4 in tibial cells verified their mesodermal origin, whereas very low levels in mandibular cells confirmed their ectodermal descent. Distinct differences in the expression pattern of bone development related genes (collagen type I, osteonectin, osteocalcin, Runx2, MSX1/2, TGF-ß1, BAMBI, TWIST1, ß-catenin) were found between the different cell types. The distinct dissimilarities in proliferation, alkaline phosphatase activity, the expression of characteristic genes, and mineralization may aid to explain the differences in bone healing time observed in mandibular bone when compared to long bones of the extremities.


Subject(s)
Mandible/physiology , Mesoderm/physiology , Neural Crest/physiology , Osteoblasts/physiology , Osteogenesis/physiology , Tibia/physiology , Alkaline Phosphatase/metabolism , Animals , Cell Growth Processes/physiology , Cells, Cultured , Mandible/cytology , Mandible/metabolism , Mesoderm/cytology , Mesoderm/metabolism , Neural Crest/cytology , Neural Crest/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Sheep , Tibia/cytology , Tibia/metabolism
9.
Acta Biomater ; 9(8): 7874-84, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23628773

ABSTRACT

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in allogenic applications. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical size segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic medium for 2weeks before implantation. Autologous and allogenic transplantation was performed using the cell-seeded scaffolds and unloaded scaffolds, while the application of autologous bone grafts served as a control group (n=6). Bone healing was assessed 12weeks after surgery by radiology, microcomputed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant differences in bone formation between the autologous and allogenic groups. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell groups and the unloaded scaffolds. The results of the study suggest that scaffold-based bone tissue engineering using allogenic cells offers the potential for an off-the-shelf product. Thus the results of this study serve as an important baseline for translation of the assessed concepts into clinical applications.


Subject(s)
Disease Models, Animal , Mesenchymal Stem Cell Transplantation/methods , Plastic Surgery Procedures/methods , Tibial Fractures/pathology , Tibial Fractures/surgery , Tissue Scaffolds , Animals , Cells, Cultured , Equipment Design , Equipment Failure Analysis , Humans , Sheep , Transplantation, Autologous/methods , Transplantation, Homologous , Treatment Outcome
10.
Orthopade ; 41(4): 268-79, 2012 Apr.
Article in German | MEDLINE | ID: mdl-22476417

ABSTRACT

STUDY GOALS: The aim of the study was to evaluate the therapeutic benefit of CaReS®, a type I collagen hydrogel-based autologous chondrocyte implantation technique, for the treatment of osteochondral defects of the knee (Outerbridge grades III and IV) within a prospective multicenter study. MATERIAL AND METHODS: A total of 116 patients in 9 clinical centers were treated with CaReS between 2003 and 2008. The Cartilage Injury Evaluation Package 2000 of the International Cartilage Repair Society (ICRS) was employed for data acquisition and included the subjective International Knee Documentation Committee score (IKDC score), the pain level (visual analog scale, VAS), the physical and mental SF-36 score, the overall treatment satisfaction and the functional IKDC status of the indexed knee. Follow-up evaluation was performed 3, 6 and 12 months after surgery and annually thereafter. RESULTS: The mean defect size treated was 5.4 ± 2.7 cm(2) with 30% of the cartilage defects being ≤4 cm(2) and 70% ≥4 cm(2). The mean follow-up period was 30.2 ± 17.4 months (minimum 12 months and maximum 60 months). The mean IKDC score significantly improved from 42.4 ± 13.8 preoperatively to 70.5 ± 18.7 (p < 0.01) in the mean follow-up period. Global pain level significantly decreased (p < 0.001) from 6.7 ± 2.2 preoperatively to 3.2 ± 3.1 at the latest follow-up. Both the physical and mental components of the SF-36 score significantly increased. At the latest follow-up 80% of the patients rated the overall treatment satisfaction as either good or very good. The functional IKDC knee status clearly improved from preoperative to the latest follow-up when 23.4% of the patients reported having no restriction of knee function (I), 56.3% had mild restriction (II), 17,2% had moderate restriction (III) and 3.1% revealed severe restriction (IV). CONCLUSIONS: The CaReS technique is a clinically effective and safe method for the reconstruction of isolated osteochondral defects of the knee joint and reveals promising clinical outcome up to 5 years after surgery. A longer follow-up period and larger patient cohorts are needed to evaluate the sustainability of CaReS treatment.


Subject(s)
Chondrocytes/transplantation , Collagen Type I/therapeutic use , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Adult , Female , Humans , Hydrogels/therapeutic use , Male , Osteoarthritis, Knee/diagnosis , Prospective Studies , Treatment Outcome
11.
Orthopade ; 41(4): 280-7, 2012 Apr.
Article in German | MEDLINE | ID: mdl-22476418

ABSTRACT

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.


Subject(s)
Bone Substitutes/therapeutic use , Guided Tissue Regeneration/instrumentation , Osteogenesis/physiology , Tibial Fractures/surgery , Tissue Scaffolds , Animals , Equipment Failure Analysis , Prosthesis Design , Sheep , Treatment Outcome
12.
J Tissue Eng Regen Med ; 5(10): 831-44, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21312337

ABSTRACT

Reviewing the available literature, one could conclude that marrow-derived mesenchymal stem cells (BMSCs) are the 'gold standard' source for bone tissue engineering applications, due to their multilineage differentiation potential and easy accessibility. However, comprehensive studies comparing their osteogenic potential with bone-derived osteoblasts (OBs) to justify the preferred application of BMSCs based on performance are few. To address these shortfalls, in the present study, ovine BMSCs and OBs seeded onto scaffolds were characterized in vitro and transplanted subcutaneously into NOD/SCID mice in combination with and without recombinant human bone morphogenetic protein 7 (rhBMP-7). It was hypothesized that cell origin, ossification type and degree of vascularization and ossification depends on the nature and commitment of transplanted cells and stimulating growth factors, such as rhBMP-7. After retrieval, specimens were analysed by biomechanical testing, µCT analysis, scanning electron microscopy/energy-dispersive X-ray spectroscopy and histo- and immunohistochemistry for osteocalcin, type II collagen and BrdU. The results showed a high degree of cell survival and proliferation ectopically, resulting in active contribution to endochondral osteogenesis. When compared to BMSCs, OBs showed a higher degree of bone deposition while OB-derived bone was of higher maturation. Stimulation with rhBMP-7 increased the rate of bone synthesis for both BMSCs and OBs, additionally promoting neovascularization and osteoclast activity. These results suggest that the origin and commitment of transplanted cells highly influence the type and degree of ossification, that rhBMP-7 represents a powerful adjuvant for bone tissue-engineering applications, and that mature bone is an adequate alternative cell source for bone tissue-engineering applications.


Subject(s)
Bone Marrow Cells , Bone Marrow Transplantation , Osteoblasts , Osteogenesis , Tibia/cytology , Tissue Scaffolds , Animals , Antigens, Differentiation/biosynthesis , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 7/pharmacology , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Osteoblasts/cytology , Osteoblasts/metabolism , Osteoblasts/transplantation , Recombinant Proteins/pharmacology , Tissue Engineering/methods , Transplantation, Heterologous
13.
Z Orthop Unfall ; 148(1): 31-8, 2010 Jan.
Article in German | MEDLINE | ID: mdl-20151353

ABSTRACT

AIM: Mesenchymal stem cells have a high therapeutic potential for the reconstruction of articular cartilage defects. In this study, a cartilage-polymer construct using mesenchymal stem cells from trabecular bone and a polylactic acid polymer was fabricated with a press-coating technique. We investigated whether cells from human trabecular bone fragments have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow and whether it is possible to reconstruct an osteochondral lesion in the nude rat with the fabricated construct. METHOD: Cells were obtained from the femoral head of patients undergoing total hip arthroplasty. The fabrication of the constructs was performed by centrifugation of 1.5x10(6) cells to a cell pellet which was then placed in a polymer block. The fabricated cell constructs were cultivated for 3 weeks in a serum-free medium, supplemented with transforming growth factor beta1. Every third day, the chondrogenic differentiation was analysed using chondrogenic and osteogenic marker genes. After three weeks the constructs were implanted into 5 mm osteochondral defects of the knee joint of nude rats. After 4 and 12 weeks histochemical and immunohistochemical analyses were performed. RESULTS: At the end of the culture period the constructs showed a proteoglycan-rich extracellular matrix with the expression of collagen types II, IX and X as well as aggrecan und COMP (cartilage oligomeric matrix protein). No osteogenic markers except collagen type I could be detected. The analysis of the in vivo experiment showed a good defect filling with a reconstructed cartilage surface along with increasing resorption of the polymer. CONCLUSION: We have shown that it is possible to fabricate cartilage-polymer constructs from trabecular bone-derived cells, and that the cells have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow. With the fabricated cartilage-polymer construct it is possible to reconstruct an osteochondral defect in the knee joint of the nude rat.


Subject(s)
Bone Regeneration/physiology , Bone and Bones/surgery , Chondrocytes/cytology , Chondrocytes/transplantation , Chondrogenesis/physiology , Disease Models, Animal , Lactic Acid , Mesenchymal Stem Cell Transplantation/methods , Polymers , Prostheses and Implants , Tissue Engineering/methods , Animals , Bone Regeneration/genetics , Cell Differentiation/genetics , Chondrogenesis/genetics , Genetic Markers/genetics , Knee Joint/pathology , Knee Joint/surgery , Male , Polyesters , Rats , Rats, Nude , Reverse Transcriptase Polymerase Chain Reaction
14.
Biomed Mater ; 4(6): 065001, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19837997

ABSTRACT

The osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (MSCs) in a collagen I hydrogel was investigated. Collagen hydrogels with 7.5 x 10(5) MSCs ml(-1) were fabricated and cultured for 6 weeks in a defined, osteogenic differentiation medium. Histochemistry revealed morphologically distinct, chondrocyte-like cells, surrounded by a sulfated proteoglycan-rich extracellular matrix in the group treated with bone morphogenetic protein 2 (BMP-2), while cells cultured with dexamethasone, ascorbate-2-phosphate, and beta-glycerophosphate displayed a spindle-shaped morphology and deposited a mineralized matrix. Real-time polymerase chain reaction (RT-PCR) analyses revealed a specific chondrogenic differentiation with the expression of cartilage-specific markers in the BMP-2-treated group and a distinct expression pattern of the osteogenic markers alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), and cbfa-1 in the group treated with an osteogenic standard medium. The collagen gels were used to engineer a cell laden medical grade epsilon-polycaprolactone (PCL)-hydrogel construct for segmental bone repair showing good bonding at the scaffold hydrogel interface and even cell distribution. The results show that MSCs cultured in a collagen I hydrogel are able to undergo a distinct osteogenic differentiation pathway when stimulated with specific differentiation factors and suggest that collagen I hydrogels are a suitable means to facilitate cell seeding of scaffolds for bone tissue engineering applications.


Subject(s)
Bone Regeneration , Collagen/chemistry , Hydrogels/chemistry , Mesenchymal Stem Cells/cytology , Polyesters/chemistry , Bone Morphogenetic Protein 2/metabolism , Cartilage/metabolism , Cartilage, Articular/metabolism , Cell Differentiation , Chondrocytes/metabolism , Humans , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Osteocalcin/metabolism , Osteogenesis , Reverse Transcriptase Polymerase Chain Reaction
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