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RAPID COMMUNICATION |
Tissue Engineering Laboratory, Rm. 237, Departments of Orthodontics (MC 841), Bioengineering, and Anatomy and Cell Biology, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612-7211, USA;
*corresponding author, jmao2{at}uic.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: TMJ • osteochondral • tissue engineering • cartilage • bone
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
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Previous attempts to tissue-engineer mandibular condyles have utilized several meritorious approaches (for review, see Glowacki, 2001) that inspired various components of the present work. For instance, chondrocytes or osteoblasts encapsulated in various hydrogels survive in vitro fabrication and synthesize cell-associated extracellular matrices (Poshusta and Anseth, 2001; Schliephake et al., 2001; Springer et al., 2001; Weng et al., 2001). Increasingly sophisticated scaffold design influences cell differentiation patterns (Hollister et al., 2002; Sherwood et al., 2002). The premolded shape of the mandibular condyle is retained after marrow-derived osteoblasts are seeded in scaffolds consisting of poly-lactic-glycolic acid or natural coral (Weng et al., 2001; Chen et al., 2002; Abukawa et al., 2003). However, an unmet challenge is to tissue-engineer a mandibular condyle from adult stem cells that differentiate into both chondrogenic and osteogenic lineages, an approach that not only mimics the developmental processes of the mandibular condyle, but also is necessary for ultimate clinical applications. Stem cells are necessary because full-thickness osteochondral defects, such as those in severe arthritis, heal poorly in the absence of corresponding tissue-forming cells (Hunziker, 2002; Lietman et al., 2002). Adult mesenchymal stem cells have advantages over embryonic stem cells for tissue engineering of the mandibular condyle, because adult mesenchymal stem cells (MSCs) can be obtained from the same individual and readily induced to differentiate into both chondrogenic and osteogenic cells (Caplan, 1994).
Hydrogels are hydrophilic polymers capable of absorbing biological fluids while serving as a three-dimensional scaffold, thus providing tissue-forming cells with a mimicked environment of the extracellular matrix (Lee and Mooney, 2001). Polyethylene-glycol-based hydrogel, such as that used in the present work, is biocompatible and has been shown to maintain the viability of encapsulated cells (Poshusta and Anseth, 2001; Burdick et al., 2002). The objective of the present study was to tissue-engineer a human-shaped mandibular condyle from a single population of rat mesenchymal stem cells that had been induced to differentiate into chondrogenic and osteogenic lineages.
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MATERIALS & METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
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Treatment of MSCs with Chondrogenic and Osteogenic Differentiation Factors
The same population of first-passage MSCs was treated separately with chondrogenic or osteogenic specially formulated medium. The chondrogenic medium was supplemented with 10 ng/mL TGF-ß1, whereas the osteogenic medium contained 100 nM dexamethasone, 10 mM ß-glycerophosphate, and 0.05 mM ascorbic acid-2-phosphate. Cultures were incubated for 1 wk in 95% air/5% CO2 at 37°C, with fresh medium change every 3-4 days.
Hydrogel Preparation and Cell Photoencapsulation
Poly(ethylene glycol) diacrylate (PEGDA) (Shearwater, Huntsville, AL, USA) was dissolved in PBS supplemented with 100 units/mL penicillin and 100 µg/mL streptomycin (Gibco) to a final solution of 10% w/v. A biocompatible ultraviolet photoinitiator, 2-hydroxy-1-[4-(hydroxyethoxy) phenyl]-2-methyl-1-propanone (Ciba, Tarrytown, NY, USA) was added to the PEGDA solution to make a final concentration of 0.05% w/v. After trypsinization and counting, MSC-derived chondrogenic and osteogenic cells were re-suspended separately in the polymer/photoinitiator solution at a concentration of 5 x 106 cells/mL.
For in vivo experiments, a 200-µL aliquot of cell/polymer suspension containing MSC-derived chondrogenic cells was loaded in the human mandibular condyle-shaped polyurethane mold (ps. 1D, 1E), followed by photopolymerization with UV light at 365 nm (Glowmark, Upper Saddle River, NJ, USA) for 5 min (Elisseeff et al., 2000). MSC-derived osteogenic cells suspended in polymer/photoinitiator solution were loaded to occupy the remainder of the mold (approx. 400 µL), followed by photopolymerization. For the in vitro assay, a 100-µL aliquot of cell/polymer suspension containing either MSC-derived chondrogenic cells or MSC-derived osteogenic cells was loaded in tissue culture inserts (diameter, 5 mm), followed by photopolymerization.
In vivo Implantation and in vitro Incubation of Hydrogel Constructs
Following photopolymerization, the osteochondral construct was removed from the mold and washed with PBS supplemented with 1% antibiotics. After anesthesia of severe combined immunodeficient (SCID) mice (four- to five-week-old males) (Harlan) by I.P. injection of 100 mg/kg ketamine plus 5 mg/kg xylazine, the osteochondral constructs were implanted into dorsal subcutaneous pockets formed by blunt dissection. Four fabricated constructs were implanted into 2 SCID mice. Three experimental constructs contained MSC-derived chondrogenic and osteogenic cells encapsulated in 2 stratified layers of poly(ethylene glycol) diacrylate hydrogel, whereas the fourth construct, containing untreated MSCs, served as a control.
To demonstrate chondrogenesis and osteogenesis in vitro, we removed the resulting constructs (6 samples per group) from the tissue culture inserts and incubated them in six-well tissue culture plates with either chondrogenic or osteogenic medium, respectively. Control samples consisted of 6 constructs encapsulating untreated MSCs and 6 constructs with no cells. Control constructs were incubated with DMEM/FBS without exposure to chondrogenic or osteogenic factors. MSC monolayer cultures (6 culture plates per group) were incubated with chondrogenic or osteogenic medium, or with DMEM/FBS as control. All hydrogel constructs and monolayer cultures for the in vitro assay were incubated statically at 95% air/5% CO2 at 37°C for 4 wks, with fresh medium change every 3-4 days.
Harvest of Tissue-engineered Mandibular Condyles and Histologic Phenotyping
Eight wks following subcutaneous implantation, tissue-engineered osteochondral constructs were harvested from SCID mice. Following the animals’ CO2 asphyxiation, an incision was made in the dorsum of the SCID mice (Fig. 1A
). After careful separation from the surrounding fibrous capsule, the tissue-engineered mandibular condyles were removed (Figs. 1B, 1C), rinsed with PBS, fixed in 10% formalin overnight, embedded in paraffin, and sectioned in the sagittal plane and parallel to the long axis of the construct at 5-µm thickness according to standard histological procedures. Sequential sections were stained with hematoxylin and eosin, toluidine blue, von Kossa’s silver stain, and safranin O/fast green so that osseous and cartilaginous phenotypes could be distinguished. The same histologic preparations were used for in vitro constructs. Monolayer cultures were stained with either safranin O or von Kosssa and alkaline phosphatase stain. A fresh mixture of Naphthol, DMF (N, N-Dimethylformamide), Tris-HCl, and red violet LB salt (Sigma) stained monolayer cultures for alkaline phosphatase, followed by standard von Kossa staining.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
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) from osteochondral constructs consisting of a single population of MSC-derived chondrogenic and osteogenic cells encapsulated in two stratified layers of PEG-based hydrogel. The tissue-engineered mandibular condyle measured 11 x 4 x 7 mm (length and height measurements in Figs. 1B and 1C, respectively), virtually the same size as the polyurethane mold of the human cadaver mandibular condyle (cf. Fig. 1E). Gross examination and physical manipulation indicated that the tissue-engineered mandibular condyles were opaque, firm, and retained the macroscopic shape of the cadaver human mandibular condyle from which the polyurethane mold was made (Figs. 1D, 1E).
Nodules of mineral deposits in the osteogenic layer containing MSC-derived osteogenic cells encapsulated in PEG-based hydrogel were revealed with von Kossa silver staining (the lower half of Fig. 2A). In contrast, the chondrogenic layer, consisting of MSC-derived chondrogenic cells encapsulated in PEG-based hydrogel, lacked mineralization nodules (the upper half of Fig. 2A). The chondrogenic layer contained sparse chondrocyte-like cells within abundant extracellular matrix that reacted positively to safranin O (Fig. 2B). Multiple islands of dark-stained structures with H & E were present in the osteogenic layer, consisting of MSC-derived osteogenic cells encapsulated in PEG-based hydrogel (Fig. 2C). Osteoblast-like cells resided on the surface and in the center of these islands. These island structures reacted positively to toluidine blue (Fig. 2D). The control construct, consisting of hydrogel encapsulating untreated-MSCs, reacted negatively to safranin O, von Kossa, and toludine blue staining (data not shown).
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), whereas the same population of MSCs cultured without TGF-ß1 showed negative reaction to safranin O (Fig. 3B). Positive reaction to safranin O was also evident after encapsulation of MSC-derived chondrogenic cells in PEG-based hydrogel, especially in the matrix after four-week incubation of the hydrogel-MSC construct in the chondrogenic medium (Fig. 3C). In contrast, the same population of MSCs without exposure to chondrogenic medium prior to encapsulation in the hydrogel showed negative reaction to safranin O (Fig. 3D).
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) and von Kossa silver stain (green arrow in Fig. 4A), indicating their osteogenic phenotype and mineral deposition, respectively. In contrast, the same population of MSCs without exposure to osteogenic medium showed negative reaction for both alkaline phosphatase and von Kossa staining (Fig. 4B). Further, the osteogenic constructs, consisting of PEG-hydrogel encapsulating MSC-derived osteogenic cells incubated in osteogenic medium for 4 wks, showed the formation of mineral nodules and positive reaction to von Kossa silver stain (Fig. 4C), whereas the same population of MSCs without exposure to osteogenic medium showed negative reaction to von Kossa staining (Fig. 4D). The PEG hydrogel encapsulating MSC-derived chondrogenic cells showed negative reaction to osteogenic markers such as von Kossa stain, whereas PEG hydrogel encapsulating MSC-derived osteogenic cells demonstrated negative reaction to chondrogenic markers such as safranin O (data not shown). In addition, control hydrogel constructs without any cells reacted negatively to both chondrogenic and osteogenic markers (data not shown).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
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Analysis of the present data demonstrates that MSC-derived chondrogenic and osteogenic cells continued their phenotypic differentiations both in vitro and in vivo. This is remarkable, since MSC-derived chondrogenic and osteogenic cells were encapsulated into the shape of a human mandibular condyle with a dimension of 11 x 4 x 7 mm. The in vitro osteogenic potential of MSC-derived osteogenic cells in the present work is evidenced by their positive reactions to alkaline phosphatase and von Kossa staining. In vitro chondrogenesis in the present work is evidenced by positive reaction to safranin O, a cationic dye that binds to cartilage-specific glycosaminoglycans such as chondroitin sulfate and keratan sulfate (Lammi and Tammi, 1988; Mao et al., 1998; Wang and Mao, 2002). On the other hand, chondrogenesis and osteogenesis in vivo were demonstrated by strong safranin O labeling of the chondrocytes’ extracellular matrix, and positive reaction to von Kossa staining as well as by the formation of dark HE-stained island structures occupied by osteoblast-like cells, respectively. Matrix synthesis by MSC-derived chondrogenic and osteogenic cells in 2 stratified, and yet integrated, layers of PEG hydrogel corroborates previous findings from the use of similar PEG-based hydrogel systems (Elisseeff et al., 2000; Poshusta and Anseth, 2001; Burdick and Anseth, 2002; Halstenberg et al., 2002; Martens et al., 2003). In the present study, histological examination of the chondrogenic layer revealed abundant safranin-O-positive matrices of chondrocyte-like cells. In contrast, the present observation of osteoblast-like cells on both the surface and the center of toluidine-blue-positive island structures warrants further characterization for genetic and biochemical osteogenic markers. The selection of eight-week in vivo implantation was based on both our preliminary data and the anticipated clinical requirement for the shortest possible ex vivo incubation time (Temenoff and Mikos, 2000; Gao et al., 2001; Altman et al., 2002).
The use of a uniform polymer such as PEG-based hydrogel for both chondral and osseous components of osteochondral constructs has additional advantages, such as the ease of fabrication, and improved adhesion and interpenetration between the 2 layers (Lu and Anseth, 1999; Lee and Mooney, 2001; Nguyen and West, 2002). In the present study, physical manipulation of the ex vivo photopolymerized constructs and the harvested in vivo constructs failed to separate the 2 layers. PEGDA is biocompatible, biodegradable, and FDA-approved for several medical applications (Fu et al., 2002). Despite a somewhat slow degradation rate, degradation of PEGDA in the present study is evident from both cell-associated matrix synthesis and formation of distinctive microscopic structures in both the chondrogenic and osteogenic layers. A common tendency associated with seeding cells in prefabricated three-dimensional scaffolds is their localization in the scaffold’s surface (e.g., Abukawa et al., 2003). In the present study, loading MSC-derived chondrogenic and osteogenic cells in PEG hydrogel solution before photopolymerization likely has allowed for relatively homogenous cell distribution. On the other hand, copolymer may be necessary to promote differential needs of chondrogenesis and osteogenesis (Schaefer et al., 2000; Gao et al., 2001; Sherwood et al., 2002).
Much additional work is needed before tissue-engineered mandibular condyles are ready for therapeutic use in patients suffering from osteoarthritis, rheumatoid arthritis, injuries, and congenital anomalies. A meritorious approach is in vivo growth factor delivery to maintain phenotypic differentiations of chondrogenic and osteogenic cells (Martin et al., 1999; Blunk et al., 2002; Burdick et al., 2002; Pei et al., 2002a). The mechanical strength of tissue-engineered mandibular condyles must be enhanced so that they are capable of withstanding the mechanical stresses that normal condyles experience. Mechanical stresses with tailored peak magnitudes and frequencies are capable of modulating bone and cartilage growth at different levels of organization in both the appendicular and craniofacial skeletal lineages (Carter et al., 1998; Goldstein, 2002; Mao, 2002; Wang and Mao, 2002; Kopher and Mao, 2003). Recently, both hydrodynamic stresses and bioreactors have been shown to enhance the biophysical properties of tissue-engineered cartilage constructs (Buschmann et al., 1995; Vunjak-Novakovic et al., 1999; Mauck et al., 2000; Altman et al., 2002; Davisson et al., 2002; Pei et al., 2002b). The enhancement of mechanical properties of tissue-engineered mandibular condyles likely will be a critical step toward clinical applications. Nonetheless, the present findings represent a proof of concept for further development of tissue-engineered mandibular condyles.
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ACKNOWLEDGMENTS |
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Received March 21, 2003; Last revision October 1, 2003; Accepted October 3, 2003
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REFERENCES |
|---|
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TOPABSTRACTINTRODUCTIONMATERIALS & METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Altman GH, Lu HH, Horan RL, Calabro T, Ryder D, Kaplan DL, et al. (2002). Advanced bioreactor with controlled application of multi-dimensional strain for tissue engineering. J Biomech Eng 124:742–749.[ISI][Medline]
Baird DN, Rea WJ (1998). The temporomandibular joint implant controversy: a review of autogenous/alloplastic materials and their complications. J Nut Env Med 8:289–300.
Bell RB, Blakey GH, White RP, Hillebrand DG, Molina A (2002). Staged reconstruction of the severely atrophic mandible with autogenous bone graft and endosteal implants. J Oral Maxillofac Surg 60:1135–1141.[ISI][Medline]
Blunk T, Sieminski AL, Gooch KJ, Courter DL, Hollander AP, Nahir AM, et al. (2002). Differential effects of growth factors on tissue-engineered cartilage. Tissue Eng 8:73–84.[ISI][Medline]
Burdick JA, Anseth KS (2002). Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 23:4315–4323.[ISI][Medline]
Burdick JA, Mason MN, Hinman AD, Thorne K, Anseth KS (2002). Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. J Control Release 83:53–63.[ISI][Medline]
Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB (1995). Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci 108:1497–1508.[Abstract]
Caplan AI (1994). The mesengenic process. Clin Plast Surg 21:429–435.[ISI][Medline]
Carter DR, Beaupre GS, Giori NJ, Helms JA (1998). Mechanobiology of skeletal regeneration. Clin Orthop 355(Suppl):S41–S55.
Chen F, Mao T, Tao K, Chen S, Ding G, Gu X (2002). Bone graft in the shape of human mandibular condyle reconstruction via seeding marrow-derived osteoblasts into porous coral in a nude mice model. J Oral Maxillofac Surg 60:1155–1159.[ISI][Medline]
Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A (2002). Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res 20:842–848.[ISI][Medline]
Elisseeff J, McIntosh W, Anseth K, Riley S, Ragan P, Langer R (2000). Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. J Biomed Mater Res 51:164–171.[ISI][Medline]
Fu J, Fiegel J, Krauland E, Hanes J (2002). New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 23:4425–4433.[ISI][Medline]
Gao J, Dennis JE, Solchaga LA, Awadallah AS, Goldberg VM, Caplan AI (2001). Tissue-engineered fabrication of an osteochondral composite graft using rat bone marrow-derived mesenchymal stem cells. Tissue Eng 7:363–371.[ISI][Medline]
Glowacki J (2001). Engineered cartilage, bone, joints, and menisci. Potential for temporomandibular joint reconstruction. Cells Tissues Organs 169:302–308.[ISI][Medline]
Goldberg VM, Caplan AI (1994). Biological resurfacing: an alternative to total joint arthroplasty. Orthopedics 17:819–821.[ISI][Medline]
Goldstein SA (2002). Tissue engineering: functional assessment and clinical outcome. Ann NY Acad Sci 961:183–192.
Halstenberg S, Panitch A, Rizzi S, Hall H, Hubbell JA (2002). Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: a cell adhesive and plasmin-degradable biosynthetic material for tissue repair. Biomacromolecules 3:710–723.[ISI][Medline]
Henning TB, Ellis E 3rd, Carlson DS (1992). Growth of the mandible following replacement of the mandibular condyle with the sternal end of the clavicle: an experimental investigation in Macaca mulatta. J Oral Maxillofac Surg 50:1196–1206.[ISI][Medline]
Hollister SJ, Maddox RD, Taboas JM (2002). Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials 3:4095–4103.
Hunziker EB (2002). Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432–463.[ISI][Medline]
Kopher RA, Mao JJ (2003). Sutural growth modulated by the oscillatory component of micromechanical strain. J Bone Miner Res 18:521–528.[ISI][Medline]
Lammi M, Tammi M (1988). Densitometric assay of nanogram quantities of proteoglycans precipitated on nitrocellulose membrane with safranin O. Anal Biochem 168:352–357.[ISI][Medline]
Lee KY, Mooney DJ (2001). Hydrogels for tissue engineering. Chem Rev 101:1869–1879.[ISI][Medline]
LeResche L (1997). Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. Crit Rev Oral Biol Med 8:291–305.
Lietman SA, Miyamoto S, Brown PR, Inoue N, Reddi AH (2002). The temporal sequence of spontaneous repair of osteochondral defects in the knees of rabbits is dependent on the geometry of the defect. J Bone Joint Surg Br 84:600–606.
Lu S, Anseth KS (1999). Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release. J Control Release 57:291–300.[ISI][Medline]
Mao JJ (2002). Mechanobiology of craniofacial sutures. J Dent Res 81:810–816.
Mao JJ, Rahemtulla F, Scott PG (1998). Proteoglycan expression in the rat temporomandibular joint in response to unilateral bite raise. J Dent Res 77:1520–1528.
Martens PJ, Bryant SJ, Anseth KS (2003). Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering. Biomacromolecules 4:283–292.[ISI][Medline]
Martin I, Vunjak-Novakovic G, Yang J, Langer R, Freed LE (1999). Mammalian chondrocytes expanded in the presence of fibroblast growth factor 2 maintain the ability to differentiate and regenerate three-dimensional cartilaginous tissue. Exp Cell Res 253:681–688.[ISI][Medline]
Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, et al. (2000). Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122:252–260.[ISI][Medline]
Nguyen KT, West JL (2002). Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314.[ISI][Medline]
Niederauer GG, Slivka MA, Leatherbury NC, Korvick DL, Harroff HH, Ehler WC, et al. (2000). Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials 21:2561–2574.[ISI][Medline]
Okeson JP (1996). Orofacial pain: guidelines for assessment, diagnosis and management. Carol Stream, IL: Quintessence Publishing Co., Inc., pp. 1-15.
Pei M, Seidel J, Vunjak-Novakovic G, Freed LE (2002a). Growth factors for sequential cellular de- and re-differentiation in tissue engineering. Biochem Biophys Res Commun 294:149–154.[ISI][Medline]
Pei M, Solchaga LA, Seidel J, Zeng L, Vunjak-Novakovic G, Caplan AI, et al. (2002b). Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J 16:1691–1694.
Poshusta AK, Anseth KS (2001). Photopolymerized biomaterials for application in the temporomandibular joint. Cells Tissues Organs 169:272–278.[ISI][Medline]
Sarnat BG, Laskin DM (1991). The temporomandibular joint: a biological basis for clinical practice. Philadelphia, PA: W.B. Saunders Publ.
Schaefer D, Martin I, Shastri P, Padera RF, Langer R, Freed LE, et al. (2000). In vitro generation of osteochondral composites. Biomaterials 21:2599–2606.[ISI][Medline]
Schliephake H, Knebel JW, Aufderheide M, Tauscher M (2001). Use of cultivated osteoprogenitor cells to increase bone formation in segmental mandibular defects: an experimental pilot study in sheep. Int J Oral Maxillofac Surg 30:531–537.[ISI][Medline]
Sherwood JK, Riley SL, Palazzolo R, Brown SC, Monkhouse DC, Coates M, et al. (2002). A three-dimensional osteochondral composite scaffold for articular cartilage repair. Biomaterials 23:4739–4751.[ISI][Medline]
Springer IN, Fleiner B, Jepsen S, Acil Y (2001). Culture of cells gained from temporomandibular joint cartilage on non-absorbable scaffolds. Biomaterials 22:2569–2577.[ISI][Medline]
Stohler CS (1999). Muscle-related temporomandibular disorders. J Orofac Pain 13:273–284.[ISI][Medline]
Temenoff JS, Mikos AG (2000). Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials 21:2405–2412.[ISI][Medline]
Vunjak-Novakovic G, Martin I, Obradovic B, Treppo S, Grodzinsky AJ, Langer R, et al. (1999). Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. J Orthop Res 17:130–138.[ISI][Medline]
Wang X, Mao JJ (2002). Accelerated chondrogenesis of the rabbit cranial base growth plate upon oscillatory mechanical stimuli. J Bone Miner Res 17:1843–1850.[ISI][Medline]
Weng Y, Cao Y, Silva CA, Vacanti MP, Vacanti CA (2001). Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. J Oral Maxillofac Surg 59:185–190.[ISI][Medline]
Wolford LM, Karras SC (1997). Autologous fat transplantation around temporomandibular joint total joint prostheses: preliminary treatment outcomes. J Oral Maxillofac Surg 55:245–251.[ISI][Medline]
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