Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep.
Ontology highlight
ABSTRACT:
SUBMITTER: Mohan N
PROVIDER: S-EPMC4977000 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep.
Mohan Neethu N Gupta Vineet V Sridharan Banu Priya BP Mellott Adam J AJ Easley Jeremiah T JT Palmer Ross H RH Galbraith Richard A RA Key Vincent H VH Berkland Cory J CJ Detamore Michael S MS
Regenerative medicine 20150929 6
<h4>Background</h4>The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage.<h4>Aim</h4>The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs.<h4>Materials & methods</h4>The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted.<h4>Results</h4>The repair tissues in the microfracture were mo ...[more]
Similar Datasets
Project description:Osseointegration, the ability for an implant to be anchored in bone tissue with direct bone-implant contact and allowing for continuous adaptive remodelling, is clinically used in different reconstructive fields, such as dentistry, orthopedics and otology. The latter uses a bone conducting sound processor connected to a skin-penetrating abutment that is mounted on a titanium implant placed in the temporal bone, thereby acting as a path for transmission of the vibrations generated by the sound processor. The success of the treatment relies on bone healing and osseointegration, which could be improved by surface modifications. The aim of this study was to evaluate the long-term osseointegration in a sheep skull model and compare a laser-ablated implant surface with a machined implant. Commercially available 4 mm titanium implants, either with a machined (Wide Ponto) or a laser-ablated surface (Ponto BHX, Oticon Medical, Sweden), were used in the current study. The surfaces were evaluated by scanning electron microscopy. The implantation was performed with a full soft tissue flap and the osteotomy was prepared using the MIPS drill kit (Oticon Medical, Sweden) prior to installation of the implants in the frontal bone of eight female sheep. After five months, biopsies including the implant and surrounding bone tissue obtained, processed and analysed using histology, histomorphometry, scanning electron microscopy and Raman spectroscopy. The animals healed well, without signs of adverse events. Histomorphometry showed a large amount of bone tissue around both implant types, with 75% of the threaded area occupied by bone for both implant types. A large amount of bone-implant contact was observed for both implant types, with 67%-71% of the surface covered by bone. Both implant types were surrounded by mature remodelled lamellar bone with high mineral content, corroborating the histological observations. The current results show that the laser-ablated surface induces healing similar to the well-known clinically used machined surface in ovine cranial bone. In conclusion, the present long-term experimental results indicate that a laser-ablated implant performs equally well as a clinically used implant with a machined surface. This, together with previously reported, improved early biomechanical anchorage, suggests future, safe and efficient clinical potential.
| S-EPMC9470750 | biostudies-literature
Project description:Extracellular matrix (ECM) "raw materials" such as demineralized bone matrix (DBM) and cartilage matrix have emerged as leading scaffolding materials for osteochondral regeneration owing to their capacity to facilitate progenitor/resident cell recruitment, infiltration, and differentiation without adding growth factors. Scaffolds comprising synthetic polymers are sturdy yet generally lack cues for guiding cell differentiation. We hypothesized that opposing gradients of decellularized cartilage (DCC) and DBM in polymeric microsphere-based scaffolds would provide superior regeneration compared to polymer-only scaffolds in vivo. Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds were fabricated, either with opposing gradients of DCC and DBM encapsulated (GRADIENT) or without DCC and DBM (BLANK control), and implanted into rabbit osteochondral defects in medial femoral condyles. After 12 weeks, gross morphological evaluation showed that the repair tissue in about 30% of the implants was either slightly or significantly depressed, hinting toward rapid polymer degradation in scaffolds from both of the groups. Additionally, no differences were observed in gross morphology of the repair tissue between the BLANK and GRADIENT groups. Mechanical testing revealed no significant differences in model parameter values between the two groups. Histological observations demonstrated that the repair tissue in both of the groups was fibrous in nature with the cells demonstrating notable proliferation and matrix deposition activity. No adverse inflammatory response was observed in any of the implants from the two groups. Overall, the results emphasize the need to improve the technology in terms of altering the DBM and DCC concentrations, and tailoring the polymer degradation to these concentrations.
| S-EPMC7423242 | biostudies-literature
Project description:Fresh osteochondral allograft transplantation has been an effective treatment option with promising long-term clinical outcomes for focal posttraumatic defects in the knee for young, active individuals. We examined histologic features of 35 fresh osteochondral allograft specimens retrieved at the time of subsequent graft revision, osteotomy, or TKA. Graft survival time ranged from 1 to 25 years based on their time to reoperation. Histologic features of early graft failures were lack of chondrocyte viability and loss of matrix cationic staining. Histologic features of late graft failures were fracture through the graft, active and incomplete remodeling of the graft bone by the host bone, and resorption of the graft tissue by synovial inflammatory activity at graft edges. Histologic features associated with long-term allograft survival included viable chondrocytes, functional preservation of matrix, and complete replacement of the graft bone with the host bone. Given chondrocyte viability, long-term allograft survival depends on graft stability by rigid fixation of host bone to graft bone. With the stable osseous graft base, the hyaline cartilage portion of the allograft can survive and function for 25 years or more.
| S-EPMC2584250 | biostudies-other
Project description:Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration.
| S-EPMC5299100 | biostudies-literature
Project description:Microtia, frequently encountered in plastic surgery practice, is usually corrected by auricular reconstruction with prostheses or autologous cartilages. In recent decades, however, cartilage tissue engineering has been emerging as a promising alternative for its minimal invasion and low immunogenicity. As a critical factor for tissue engineering, scaffolds are expected to be sufficiently porous and stiff to facilitate chondrogenesis. In this work, we introduce novel poly-l-lactic acid (PLLA) porous microsphere-reinforced silk-based hybrid (SBH) scaffolds with a multihierarchical porous structure. The scaffolds are fabricated by embedding PLLA porous microspheres (PMs) into a blending matrix of silk fibroin (SF) and gelatin solution, followed by mixing with a degummed silk fiber mesh and freeze-drying process. Through adjusting the amount of PLLA PMs, the mechanical strength approximates to natural cartilage and also balanced physical properties were realized. Biological evaluations of SBH scaffolds, both in vitro and in vivo, were conducted and PM-free plain silk-based (PSB) scaffolds were applied as control. Overall, it suggests that the incorporation of PLLA PMs remarkably improves mechanical properties and the capability to promote chondrogenesis of SBH scaffolds, and that SBH scaffolds appear to be a promising construct for potential applications in auricular cartilage tissue engineering and relevant fields.
| S-EPMC7860514 | biostudies-literature
Project description:The study aims to test the long-term stability of gradient characteristics for model-based correction of diffusion weighting (DW) bias in an apparent diffusion coefficient (ADC) for multisite imaging trials. Single spin echo (SSE) DWI of a long-tube ice-water phantom was acquired quarterly on six MR scanners over two years for individual diffusion gradient channels, along with B0 mapping, as a function of right-left (RL) and superior-inferior (SI) offsets from the isocenter. Additional double spin-echo (DSE) DWI was performed on two systems. The offset dependences of derived ADC were fit to 4th-order polynomials. Chronic shim gradients were measured from spatial derivatives of B0 maps along the tube direction. Gradient nonlinearity (GNL) was modeled using vendor-provided gradient field descriptions. Deviations were quantified by root-mean-square differences (RMSD), normalized to reference ice-water ADC, between the model and reference (RMSDREF), measurement and model (RMSDEXP), and temporal measurement variations (RMSDTMP). Average RMSDREF was 4.9 ± 3.2 (%RL) and -14.8 ± 3.8 (%SI), and threefold larger than RMSDEXP. RMSDTMP was close to measurement errors (~3%). GNL-induced bias across gradient systems varied up to 20%, while deviation from the model accounted at most for 6.5%, and temporal variation for less than 3% of ADC reproducibility error. Higher SSE RMSDEXP = 7.5-11% was reduced to 2.5-4.8% by DSE, consistent with the eddy current origin. Measured chronic shim gradients below 0.1 mT/m had a minor contribution to ADC bias. The demonstrated long-term stability of spatial ADC profiles and consistency with system GNL models justifies retrospective and prospective DW bias correction based on system gradient design models. Residual errors due to eddy currents and shim gradients should be corrected independent of GNL.
| S-EPMC8875771 | biostudies-literature
Project description:The purpose of this study was to characterize and determine the efficacy of a long-term, non-invasive gel/microsphere (GMS) eye drop for glaucoma. This novel drug delivery system is comprised of a thermoresponsive hydrogel carrier and drug-loaded polymer microspheres. In vitro release of brimonidine from the GMS drops and gel properties were quantified. A single brimonidine-loaded GMS drop was administered to 5 normotensive rabbits and intraocular pressure (IOP) was monitored for 28 days. Here we report that IOP reduction in rabbits receiving a single brimonidine GMS drop was comparable to that of rabbits receiving twice daily, standard brimonidine drops. GMS drops were retained in the inferior fornix in all animals for the length of the study. Our results suggest in vivo efficacy over 28 days from a single GMS drop and a potential decrease in systemic absorption, based on a lack of substantial IOP effects on the fellow untreated eye, compared to brimonidine twice-daily eye drops. To our knowledge, this represents the first long-term, drug-releasing depot that can be administered as a traditional eye drop.
| S-EPMC5561248 | biostudies-literature
Project description:Temporally and spatially controlled delivery of growth factors in polymeric scaffolds is crucial for engineering composite tissue structures, such as osteochondral constructs. In the present study, microsphere-mediated growth factor delivery in polymer scaffolds and its impact on osteochondral differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) was evaluated. Two growth factors, bone morphogenetic protein 2 (rhBMP-2) and insulin-like growth factor I (rhIGF-I), were incorporated as a single concentration gradient or reverse gradient combining two factors in the scaffolds. To assess the gradient making system and the delivery efficiency of polylactic-co-glycolic acid (PLGA) and silk fibroin microspheres, initially an alginate gel was fabricated into a cylinder shape with microspheres incorporated as gradients. Compared to PLGA microspheres, silk microspheres were more efficient in delivering rhBMP-2, probably due to sustained release of the growth factor, while less efficient in delivering rhIGF-I, likely due to loading efficiency. The growth factor gradients formed were shallow, inducing non-gradient trends in hMSC osteochondral differentiation. Aqueous-derived silk porous scaffolds were used to incorporate silk microspheres using the same gradient process. Both growth factors formed deep and linear concentration gradients in the scaffold, as shown by enzyme-linked immunosorbent assay (ELISA). After seeding with hMSCs and culturing for 5 weeks in a medium containing osteogenic and chondrogenic components, hMSCs exhibited osteogenic and chondrogenic differentiation along the concentration gradients of rhBMP-2 in the single gradient of rhBMP-2 and reverse gradient of rhBMP-2/rhIGF-I, but not the rhIGF-I gradient system, confirming that silk microspheres were more efficient in delivering rhBMP-2 than rhIGF-I for hMSCs osteochondrogenesis. This novel silk microsphere/scaffold system offers a new option for the delivery of multiple growth factors with spatial control in a 3D culture environment for both understanding natural tissue growth process and in vitro engineering complex tissue constructs.
| S-EPMC2698962 | biostudies-literature
Project description:Osteochondral defects (OCD) cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation. Conventional strategies, such as the control of implant microstructure or the introduction of growth factors, have limited functions failing to manage these complex environments. Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes (CuTA@SF) to provide a suitable microenvironment for enhanced OCD regeneration. The incorporation of CuTA nanozymes endowed the SF hydrogel with a uniform microstructure and elevated hydrophilicity. In vitro cultivation of mesenchymal stem cells (MSCs) and chondrocytes showed that CuTA@SF hydrogel accelerated cell proliferation and enhanced cell viability, as well as had antioxidant and antibacterial properties. Under the inflammatory environment with the stimulation of IL-1β, CuTA@SF hydrogel still possessed the potential to promote MSC osteogenesis and deposition of cartilage-specific extracellular matrix (ECM). The proteomics analysis further confirmed that CuTA@SF hydrogel promoted cell proliferation and ECM synthesis. In the full-thickness OCD model of rabbit, CuTA@SF hydrogel displayed successfully in situ OCD regeneration, as evidenced by micro-CT, histology (HE, S/O, and toluidine blue staining) and immunohistochemistry (Col I and aggrecan immunostaining). Therefore, CuTA@SF hydrogel is a promising biomaterial targeted at the regeneration of OCD.
| S-EPMC9163388 | biostudies-literature
Project description:F344 rats were divided into 4 groups: vehicle control, DEN, DEN+CLO and CLO. After one week of basal diet, rats belonging to the groups DEN and DEN+CLO underwent intraperitoneal injection of DEN (30mg/kg body weight) dissolved in NaCl 9‰. The two other groups were injected with NaCl 9‰ alone. At 30mg/kg, DEN is non-necrogenic thus only exhibiting initiating properties. Twelve days after injection, diet from rats belonging to the groups CLO and DEN+CLO was changed for diet containing 5000ppm CLO for up to 608 days. Series of 5 rats from each group were necropsied at days 18, 46, 102, 264, 377, 447 (reverse phase from day 377: no more CLO in the diet for rats belonging to the DEN+CLO group), and for the CLO and Control group 524, and 608 days after the injection of DEN or saline. From day 524, half of the CLO-treated rats were kept on basal diet (reverse phase) until day 608. Keywords = Clofibric acid Keywords = Diethylnitrosamine Keywords = Rat Keywords: other
2005-03-01 | GSE2216 | GEO