ABSTRACT
INTRODUCTION: This article reports, after at least 10 years of follow-up, the comparative data of marginal bone loss (MBL) and periimplant soft tissue parameters, around implant with and without laser-microtextured (L) collar surface, previously reported at 3 years of follow-up. MATERIALS AND METHODS: Twenty implants with L collar surface (test) were placed adjacent to 20 control implants with machined (M) collar surface in 15 partially edentulous patients, who were followed up for at least 10 years as part of a prospective longitudinal study. The plaque score, bleeding on probing (BoP) score, and probing depth (PD) were recorded at baseline and at each year follow-up examination. Mucosal recession (MR), and radiographic MBL were assessed at baseline and after at least 10 years. RESULTS: Four patients were lost during follow-up, so the number of implants that have been followed for at least 10 years was 32 (16 tests and 16 controls). At the end of the follow-up period, no significant differences were found between the study groups regarding the presence of plaque and BoP (P > 0.05). A statistically significant difference between test and control implant was found for mean PD (2.3 ± 0.7 mm vs 3.8 ± 0.8), MBL (1.23 ± 0.21 mm vs 2.8 ± 0.9 mm), and mean MR (1.08 ± 0.4 mm vs 2.46 ± 0.3 mm). CONCLUSION: Results suggest that after at least 10 years of function, implants with laser-microtexturing (L) collar surface, compared with implants with machined surface, lead to lower MBL and PD.
Subject(s)
Alveolar Bone Loss/diagnostic imaging , Dental Implants , Dental Prosthesis Design/methods , Alveolar Bone Loss/epidemiology , Alveolar Bone Loss/etiology , Dental Implants/adverse effects , Dental Plaque Index , Female , Humans , Lasers , Male , Periodontal Index , Radiography, DentalABSTRACT
The purpose of this in vitro study was to develop calcium sulfate (CS)-based disks infused with an antimicrobial drug, which can be used as a post-surgical treatment modality for osteomyelitis. CS powder was embedded with 10% antibiotic, amoxicillin (AMX) or moxifloxacin (MFX), to form composite disks 11 mm in diameter that were tested for their degradation and antibiotic release profiles. For the disk degradation study portion, the single drug-loaded disks were placed in individual meshes, subsequently submerged in phosphate-buffered saline (PBS), and incubated at 37 °C. The disks were weighed once every seven days and analyzed via Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and scanning electron microscopy. During the antibiotic release analysis, composite disks were placed in PBS solution, which was changed every 3 days, and analyzed for antibiotic activity and efficacy. The antibacterial effects of these sustained-release composites were tested by agar diffusion assay using Streptococcus mutans (S. mutans) UA 159 as an indicator strain. The degradation data showed significant increases in the degradation of all disks with the addition of antibiotics. Following PBS incubation, there were significant increases in the amount of phosphate and decreases in the amount of sulfate. The agar diffusion assay demonstrated that the released concentrations of the respective antibiotics from the disks were significantly higher than the minimum inhibitory concentration exhibited against S. mutans over a 2-3-week period. In conclusion, CS-antibiotic composite disks can potentially serve as a resorbable, osteoconductive, and antibacterial therapy in the treatment of bone defects and osteomyelitis.
ABSTRACT
There are several significant issues that prevent us from growing a human arm now, or within the next 10-20 years. From a tissue engineering perspective, while we can grow many of the components necessary for construction of a human arm, we can only grow them in relatively small volumes, and when scaled up to large volumes we lack the ability to develop adequate blood/nerve supply. From a genetic engineering perspective, we will probably never be able to turn on the specific genes necessary to "grow an arm" unless it is attached to a fetus and this presents enormous ethical issues related to farming of human organs and structures. Perhaps the most daunting problem facing the transplantation of a tissue engineered or transplanted arm is that of re-innervation of the structure. Since the sensory and motor nerve cells of the arm are located outside of the structure, re-innervation requires those nerves to regenerate over relatively large distances to repopulate the nervous system of the arm. This is something with which we have had little success. We can grow repair parts, but "growing an arm" presents too many insurmountable problems. The best we could possibly do with tissue engineering or genetic engineering would be the equivalent of a fetal arm and the technical problems, costs, and ethical hurdles are enormous. A more likely solution is a functional, permanent, neuroelectronically-controlled prosthesis. These are nearly a reality today.
Subject(s)
Arm/physiology , Regeneration , Animals , Genetic Engineering , Humans , Models, Animal , Salamandridae/physiology , Tissue EngineeringABSTRACT
Regeneration and preservation of bone after the extraction of a tooth are necessary for the placement of a dental implant. The goal is to regenerate alveolar bone with minimal postoperative pain. Medical grade calcium sulfate hemihydrate (MGCSH) can be used alone or in combination with other bone grafts; it improves graft handling characteristics and particle containment of particle-based bone grafts. In this case series, a 1:1 ratio mix of MGCSH and mineralized irradiated cancellous bone allograft (MICBA) was mixed with saline and grafted into an extraction socket in an effort to maintain alveolar height and width for future implant placement. MGCSH can be used in combination with other bone grafts and can improve handling characteristics and graft particle containment of particle-based bone grafts. In the cases described, we found that an MGCSH:MICBA graft can potentially be an effective bone graft composite. It has the ability to act as a space maintainer and as an osteoconductive trellis for bone cells, thereby promoting bone regeneration in the extraction socket. MGCSH, a cost-effective option, successfully improved MICBA handling characteristics, prevented soft tissue ingrowth, and assisted in the regeneration of bone.
Subject(s)
Alveolar Ridge Augmentation/methods , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Calcium Sulfate/therapeutic use , Sinus Floor Augmentation/methods , Tooth Socket/surgery , Aged , Alveolar Bone Loss/surgery , Biocompatible Materials/chemistry , Bone Regeneration/physiology , Female , Follow-Up Studies , Humans , Male , Mandible/surgery , Maxilla/surgery , Membranes, Artificial , Middle Aged , Polytetrafluoroethylene/chemistry , Tissue ScaffoldsABSTRACT
BACKGROUND: While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. OBJECTIVE: The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to ß-Tricalcium phosphate (ß-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells in vitro. METHODS: MBG, BG 45S5, and ß-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (µ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). RESULTS: Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in ß-TCP scaffolds compared to BG 45S5 and MBG groups. CONCLUSION: All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.
Subject(s)
Osteogenesis , Tissue Scaffolds , Humans , Tissue Scaffolds/chemistry , Regenerative Medicine , X-Ray Microtomography , Glass/chemistry , Ceramics/chemistry , Printing, Three-DimensionalABSTRACT
Solid freeform fabrication techniques such as direct write technology can be used to fabricate tissue-engineering scaffolds in 3 dimensions with high levels of reproducibility and precision. These can comprise complex structures made of osteoconductive, remodelable lattices to conduct bone ingrowth and solid barriers to prevent soft tissue invasion. As such, they act as a combination of bone graft and barrier membrane. Results from animal studies have shown that these structures fill rapidly with healing bone and can conduct bone across critical-size defects to fill large defects in rabbit skull. Results indicate that this technology can be used to produce both off-the-shelf and custom-fabricated bone graft substitutes. These may initially be used to restore alveolar ridge defects, but could also be used, in the future, to repair or replace complex craniofacial bone defects such as cleft palate defects. In the more distant future, these technologies could be combined with controlled-release bioactive substances such as growth factors and pharmaceuticals to regenerate complex structures comprising multiple tissue types.
Subject(s)
Bone Substitutes/chemistry , Computer-Aided Design , Facial Bones/surgery , Plastic Surgery Procedures/methods , Skull/surgery , Tissue Scaffolds/chemistry , Absorbable Implants , Animals , Biocompatible Materials/chemistry , Bone Diseases/surgery , Bone Regeneration/physiology , Bone Remodeling/physiology , Calcium Phosphates/chemistry , Cell Culture Techniques , Colloids/chemistry , Delayed-Action Preparations , Durapatite/chemistry , Elastic Modulus , Intercellular Signaling Peptides and Proteins/therapeutic use , Osteogenesis/physiology , Parietal Bone/pathology , Porosity , Prosthesis Design , Rabbits , Tissue Engineering/instrumentation , Tissue Engineering/methods , ViscosityABSTRACT
Microporous scaffolds designed to improve bony repair have had limited success; therefore, we sought to evaluate whether time-released porous scaffolds with or without recombinant bone morphogenetic protein 2 (rhBMP-2) could enhance stem cell osteoinduction. Custom-made 15/85 hydroxyapatite/ß-tricalcium phosphate scaffolds were left empty (E) or filled with rhBMP-2 (E+), calcium sulfate (CS), or CS and rhBMP-2 (CS+). All scaffolds were placed in media and weighed daily. Conditioned supernatant was analyzed for rhBMP-2 and then used to feed human adipose-derived mesenchymal stem cells (ASCs). Adipose-derived mesenchymal stem cell ALP activity, OSTERIX expression, and bone nodule formation were determined. E scaffolds retained 97% (SD, 2%) of the initial weight, whereas CS scaffolds had a near-linear 30% (SD, 3%) decrease over 60 days. E+ scaffolds released 155 (SD, 5) ng of rhBMP-2 (77%) by day 2. In contrast, CS+ scaffolds released only 30 (SD, 2) ng (10%) by day 2, and the remaining rhBMP-2 was released over 20 days. Conditioned media from E+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ACSs on day 2. However, after day 6, media from CS+ scaffolds stimulated the highest ALP activity and OSTERIX expression in ASCs. Adipose-derived mesenchymal stem cells exposed to day 8 CS+-conditioned media produced significantly more bone nodules (10.1 [SD, 1.7] nodules per high-power field) than all other scaffolds. Interestingly, day 8 conditioned media from CS scaffolds simulated significantly more bone nodules than either E or E+ scaffold (P < 0.05 for both). Time-released hydroxyapatite/ß-tricalcium phosphate porosity provides sustained growth factor release, enhances ASC osteoinduction, and may result in better in vivo bone formation.
Subject(s)
Adipose Tissue/cytology , Bone Morphogenetic Protein 2/pharmacology , Bone Regeneration/physiology , Calcium Phosphates/pharmacology , Durapatite/pharmacology , Mesenchymal Stem Cells/metabolism , Tissue Engineering/instrumentation , Tissue Scaffolds , Transforming Growth Factor beta/pharmacology , Alkaline Phosphatase/metabolism , Analysis of Variance , Calcium Sulfate/pharmacology , Cell Culture Techniques , Cell Differentiation , Enzyme-Linked Immunosorbent Assay , Humans , Porosity , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Sp7 Transcription Factor , Staining and Labeling , Transcription Factors/metabolismABSTRACT
OBJECTIVE: To evaluate a novel method of detecting and comparing the porosity of white Mineral Trioxide Aggregate and Portland cement at two different pH. MATERIALS AND METHODS: Cylindrical specimens (n = 120) were prepared from hydrated ordinary white Portland Cement (WPC) (n = 60) and white Mineral Trioxide Aggregate (WMTA) (n = 60) and exposed to environments with pH of 4.4 (n = 30) or 7.4 (n = 30). The pore size distribution and total pore volume were detected using Mercury Intrusion Porosimetry. Data were analyzed by analysis of variance and post-hoc Tukey or Tamhane test (p = 0.05). RESULTS: The pore volume of WMTA was significantly lesser than WPC at both pH (p < 0.05). The surface tension of mercury was taken as 480 (N/m) and the contact angle 141.3° for both materials. Pores were consistently found in all specimens. Total pore volumes for WPC and WMTA (cubic centimeter/gram) were 0.1954 and 0.1023, respectively, while the diameter of the pores ranged from 50-100 Å and 20-50 Å, respectively. CONCLUSIONS: Mercury Intrusion Porosimetry technique is a promising and reliable technique for assessing the porosity of endodontic materials.
Subject(s)
Aluminum Compounds , Calcium Compounds , Mercury/chemistry , Oxides , Root Canal Filling Materials , Silicates , Dental Cements , Dental Leakage/prevention & control , Drug Combinations , Feasibility Studies , Hydrogen-Ion Concentration , Materials Testing/methods , Permeability , PorosityABSTRACT
Where does dentistry fit into the field of regenerative medicine? Based on the fact that the goal of regenerative medicine is to restore function to damaged organs and tissues, it is apparent that dentistry, which has long embraced the concept of restoring function of damaged teeth, has embraced this goal from the very beginning. In this brief review we present the opinion that if you take as the primary criterion the restoration of tissue and organ function, dentistry has not only been at the forefront of restorative medicine but actually predates it in practice. We illustrate the depth and breadth of dental regenerative medicine using examples of therapies or potential therapies from our laboratories. These begin with an example from a historical area of strength, dental implant design and fabrication, progress to a more high tech bone scaffold fabrication project, and finish with a stem cell-based soft tissue engineering project. In the final analysis we believe that the restorative nature of dentistry will keep it at the forefront of regenerative medicine.
Subject(s)
Dental Implants , Regenerative Medicine , Tissue Scaffolds , Adult Stem Cells , Animals , Bone Regeneration , Bone Substitutes , Dental Prosthesis Design , Humans , Surface PropertiesABSTRACT
Deep bone defects are caused by the progression of periodontal disease, which breaks down bone and connective tissue that hold teeth in place. In this case, a 37-year-old male patient presented a deep bone defect with advanced periodontal disease around an upper canine. Medical-grade calcium sulfate was mixed with demineralized freeze-dried bone allograft and used to repair and regenerate the defect. Analysis of the radiographs at the 5-month time point showed the bone had completely regenerated.
Subject(s)
Alveolar Bone Loss/surgery , Bone Regeneration , Bone Transplantation/methods , Calcium Sulfate/pharmacology , Guided Tissue Regeneration, Periodontal/methods , Membranes, Artificial , Adult , Bone Regeneration/drug effects , Bone Substitutes , Cuspid , Humans , Male , Maxilla/surgeryABSTRACT
INTRODUCTION: A tapered dental implant (Laser-Lok [LL] surface treatment) with a 2 mm wide collar, that has been laser micromachined in the lower 1.5 mm to preferentially accomplish bone and connective tissue attachment while inhibiting epithelial downgrowth, was evaluated in a prospective, controlled, multicenter clinical trial. MATERIALS: Data are reported at measurement periods from 1 to 37 months postoperative for 20 pairs of implants in 15 patients. The implants are placed adjacent to machined collar control implants of the same design. Measurement values are reported for bleeding index, plaque index, probing depth, and crestal bone loss. RESULTS: No statistical differences are measured for either bleeding or plaque index. At all measurement periods there are significant differences in the probing depths and the crestal bone loss differences are significant after 7 months (P < 0.001). At 37 months the mean probing depth is 2.30 mm and the mean crestal bone loss is 0.59 mm for LL versus 3.60 and 1.94 mm, respectively, for control implant. Also, comparing results in the mandible versus those in the maxilla demonstrates a bigger difference (control implant - LL) in the mean in crestal bone loss and probing depth in the maxilla. However, this result was not statistically significant. DISCUSSION: The consistent difference in probing depth between LL and control implant demonstrates the formation of a stable soft-tissue seal above the crestal bone. LL limited the crestal bone loss to the 0.59 mm range as opposed to the 1.94 mm crestal bone loss reported for control implant. The LL implant was found to be comparable with the control implant in safety endpoints plaque index and sulcular bleeding index. There is a nonstatistically significant suggestion that the LL crestal bone retention superiority is greater in the maxilla than the mandible.
Subject(s)
Dental Implants , Dental Prosthesis Design , Lasers , Osseointegration/physiology , Periodontal Ligament/physiology , Adult , Aged , Alveolar Bone Loss/classification , Alveolar Process/pathology , Connective Tissue/pathology , Dental Plaque Index , Female , Follow-Up Studies , Gingival Hemorrhage/classification , Humans , Male , Mandible/surgery , Maxilla/surgery , Middle Aged , Periodontal Index , Periodontal Ligament/pathology , Periodontal Pocket/classification , Prospective Studies , Surface Properties , Wound Healing/physiologyABSTRACT
PURPOSE: The purpose of this study was to examine the crestal bone, connective tissue, and epithelial cell response to a laser microtextured collar compared with a machined collar, in the dog model. MATERIALS: Six mongrel dogs had mandibular premolars and first molars extracted and after healing replaced with BioLok implants 4 x 8 mm. Each dog had 3 control implants placed on one side of the mandible and 3 experimental, laser microtextured, implants placed contralaterally. After 3 months, 1 dog was killed. Bridges were placed on the implants of 4 of the dogs. The sixth dog served as a negative control for the duration of the experiment. Two of the dogs were killed 3 months after loading, of the dogs were killed 6 months after loading as was the negative (unloaded) control. Histology, electron microscopy, and histomorpho-metric analysis was done on histologic sections obtained from block sections of the mandible containing the implants. RESULTS: Initially the experimental implants showed greater bone attachment along the collar. With time the bone heights along the control and experimental collars were equivalent. However, the controls had more soft tissue downgrowth, greater osteoclastic activity, and increased saucerization compared with sites adjacent to experimental implants. There was closer adaptation of the bone to the laser microtextured collars. CONCLUSION: Use of tissue-engineered collars with microgrooving seems to promote bone and soft tissue attachment along the collar and facilitate development of a biological width.
Subject(s)
Dental Etching/instrumentation , Dental Implants , Dental Prosthesis Design , Osseointegration , Animals , Cell Adhesion , Connective Tissue Cells/physiology , Dental Implantation, Endosseous , Dogs , Epithelial Attachment/physiology , Epithelial Cells/physiology , Gingiva/physiology , Lasers , Surface PropertiesABSTRACT
The in vivo bone response of 3D periodic hydroxyapatite (HA) scaffolds is investigated. Two groups of HA scaffolds (11 mm diameter x 3.5 mm thick) are fabricated by direct-write assembly of a concentrated HA ink. The scaffolds consist of cylindrical rods periodically arranged into four quadrants with varying separation distances between rods. In the first group, HA rods (250 microm in diameter) are patterned to create pore channels, whose areal dimensions are 250 x 250 microm(2) in quadrant 1, 250 x 500 microm(2) in quadrants 2 and 4, and 500 x 500 microm(2) in quadrant 3. In the second group, HA rods (400 microm in diameter) are patterned to create pore channels, whose areal dimensions of 500 x 500 microm(2) in quadrant 1, 500 x 750 microm(2) in quadrants 2 and 4, and 750 x 750 microm(2) in quadrant 3. Each group of scaffolds is partially densified by sintering at 1200 degrees C prior to being implanted bilaterally in trephine defects of skeletally mature New Zealand White rabbits. Their tissue response is evaluated at 8 and 16 weeks using micro-computed tomography, histology, and scanning electron microscopy. New trabecular bone is conducted rapidly and efficiently across substantial distances within these patterned 3D HA scaffolds. Our observations suggest that HA rods are first coated with a layer of new bone followed by subsequent scaffold infilling via outward and inward radial growth of the coated regions. Direct-write assembly of 3D periodic scaffolds composed of micro-porous HA rods arrayed to produce macro-pores that are size-matched to trabecular bone may represent an optimal strategy for bone repair and replacement structures.
Subject(s)
Bone Regeneration , Bone Substitutes , Durapatite , Tissue Scaffolds , Animals , Ink , Materials Testing , Porosity , Rabbits , Skull Fractures/therapyABSTRACT
Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3D) printing technology we have created custom 3D scaffolds of hydroxyapatite (HA)/beta-tri-calcium phosphate (ß-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. Nearly 15% HA:85% ß-TCP scaffolds were designed using Robocad software, fabricated using a 3D Robocasting system, and sintered at 1100°C for 4 h. Scaffolds were coated with BMP-2 (200 ng mL-1 ), dypiridamole 100 µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3 mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. Micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/ß-TCP-dipyridamole and HA/ß-TCP-BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4, and 8 weeks (n = 5 per group; p ≤ 0.05, p ≤ 0.05, and p ≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/ß-TCP- dipyridamole and HA/ß-TCP-BMP-2 scaffolds. Coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/ß-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 366-375, 2017.
Subject(s)
Bone Morphogenetic Protein 2 , Bone Regeneration/drug effects , Calcium Phosphates , Coated Materials, Biocompatible , Dipyridamole , Durapatite , Printing, Three-Dimensional , Skull , Tissue Scaffolds/chemistry , Animals , Bone Morphogenetic Protein 2/chemistry , Bone Morphogenetic Protein 2/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Dipyridamole/chemistry , Dipyridamole/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Mice , Mice, Knockout , Skull/injuries , Skull/metabolism , Skull/pathologyABSTRACT
The treatment of peri-implant disease is one of the most controversial topics in implant dentistry. The multifactorial etiology and the myriad proposed techniques for managing the problem make successful decontamination of an implant surface affected by peri-implantitis one of the more unpredictable challenges dental practitioners have to face. This article presents the first known published case report demonstrating human histologic evidence of reosseointegration using a plastic curette for mechanical debridement and dilute sodium hypochlorite, hydrogen peroxide, and sterile saline for chemical detoxification. Guided bone regeneration in the infrabony component of the peri-implantitis lesion was accomplished using calcium sulfate and bovine bone as grafting materials and a porcine collagen barrier for connective tissue and epithelial exclusion.
ABSTRACT
Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd.
Subject(s)
Calcium Phosphates/chemistry , Cell Culture Techniques/methods , Durapatite/chemistry , Mesenchymal Stem Cells/metabolism , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Bone and Bones/metabolism , Cell Line , Humans , Mesenchymal Stem Cells/cytology , MiceABSTRACT
Osteoconductive mineral coatings represent an established technology for enhancing the integration of orthopedic implants with living bone. However, current coatings have limitations related to fabrication methods, attachment strength to metal substrates, and in vivo performance. Low temperature biomimetic growth is a coating technique wherein the device to be coated is immersed in a meta-stable saturated solution of the coating constituents and growth of the coating is then allowed to proceed on the surface of the device. This study focused on the in vivo evaluation of a biomimetic apatite coating fabricated under these conditions. The experiment was designed to specifically test the amount of bone ingrowth into the coated channels versus the uncoated channels of an established bone chamber system, with emphasis placed on the amount of bone present on the coupon surface. Three types of measurements were taken on each channel: linear ingrowth %, area ingrowth %, and continuous bone apposition %. The experiments demonstrated that under controlled conditions, the apatite coating appears to resorb in 8 weeks and did stimulate early osseointegration with the metal surface with a reduction in fibrous tissue encapsulation. This coating may, therefore, be useful in facilitating early bone ingrowth into porous surfaces without the potential for coating debris, macrophage infiltration, fibrous tissue encapsulation, and eventual coating failure as may occur with current plasma-sprayed hydroxapatite coating techniques.
Subject(s)
Apatites , Biomimetic Materials , Coated Materials, Biocompatible , Titanium , Animals , Dogs , Femur/physiology , Time FactorsABSTRACT
The current study analyzes the in vivo performance of porous sintered hydroxyapatite (HA) bone repair scaffolds fabricated using the TheriForm solid freeform fabrication process. Porous HA scaffolds with engineered macroscopic channels had a significantly higher percentage of new bone area compared with porous HA scaffolds without channels in a rabbit calvarial defect model at an 8-week time point. An unexpected finding was the unusually large amount of new bone within the base material structure, which contained pores less than 20 microm in size. Compared with composite scaffolds of 80% polylactic-co-glycolic acid and 20% beta-tricalcium phosphate with the same macroscopic architecture as evaluated in a previous study, the porous HA scaffolds with channels had a significantly higher percentage of new bone area. Therefore, the current study indicates that scaffold geometry, as determined by the fabrication process, can enhance the ability of a ceramic material to accelerate healing of calvarial defects.
Subject(s)
Biocompatible Materials/chemistry , Bone Regeneration/physiology , Bone Substitutes/chemistry , Hydroxyapatites/chemistry , Osseointegration , Tissue Engineering/methods , Animals , Biocompatible Materials/metabolism , Bone Substitutes/metabolism , Calcium Phosphates/chemistry , Calcium Phosphates/metabolism , Hydroxyapatites/metabolism , Implants, Experimental , Lactic Acid/chemistry , Lactic Acid/metabolism , Male , Materials Testing , Polyglycolic Acid/chemistry , Polyglycolic Acid/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/chemistry , Polymers/metabolism , Rabbits , Skull/cytology , Skull/pathology , Skull/surgeryABSTRACT
Tight control of pore architecture in porous scaffolds for bone repair is critical for a fully elucidated tissue response. Solid freeform fabrication (SFF) enables construction of scaffolds with tightly controlled pore architecture. Four types of porous scaffolds were constructed using SFF and evaluated in an 8-mm rabbit trephine defect at 8 and 16 weeks (n = 6): a lactide/glycolide (50:50) copolymer scaffold with 20% w/w tri-calcium phosphate and random porous architecture (Group 1); another identical design made from poly(desaminotyrosyl-tyrosine ethyl ester carbonate) [poly(DTE carbonate)], a tyrosine-derived pseudo-polyamino acid (Group 2); and two poly(DTE carbonate) scaffolds containing 500 microm pores separated by 500-microm thick walls, one type with solid walls (Group 3), and one type with microporous walls (Group 4). A commercially available coralline scaffold (Interpore) with a 486-microm average pore size and empty defects were used as controls. There was no significant difference in the overall amount of bone ingrowth in any of the devices, as found by radiographic analysis, but patterns of bone formation matched the morphology of the scaffold. These results suggest that controlled scaffold architecture can be superimposed on biomaterial composition to design and construct scaffolds with improved fill time.
Subject(s)
Bone Substitutes/metabolism , Bone and Bones/physiology , Fracture Healing/physiology , Tissue Engineering , Animals , Models, Biological , Rabbits , Skull/physiology , TrephiningABSTRACT
This study analyzed the in vivo performance of composite degradable bone repair products fabricated using the TheriForm process, a solid freeform fabrication (SFF) technique, in a rabbit calvarial defect model at 8 weeks. Scaffolds were composed of polylactic-co-glycolic acid (PLGA) polymer with 20% w/w beta-tricalcium phosphate (beta-TCP) ceramic with engineered macroscopic channels, a controlled porosity gradient, and a controlled pore size for promotion of new bone ingrowth. Scaffolds with engineered macroscopic channels and a porosity gradient had higher percentages of new bone area compared to scaffolds without engineered channels. These scaffolds also had higher percentages of new bone area compared to unfilled control defects, suggesting that scaffold material and design combinations could be tailored to facilitate filling of bony defects. This proof-of-concept study demonstrated that channel size, porosity, and pore size can be controlled and used to influence new bone formation and calvarial defect healing.