scholarly journals An endochondral ossification approach to early stage bone repair: Use of tissue‐engineered hypertrophic cartilage constructs as primordial templates for weight‐bearing bone repair

2018 ◽  
Vol 12 (4) ◽  
pp. e2147-e2150 ◽  
Author(s):  
Amos Matsiko ◽  
Emmet M. Thompson ◽  
Cai Lloyd‐Griffith ◽  
Gráinne M. Cunniffe ◽  
Tatiana Vinardell ◽  
...  

2021 ◽  
Vol 12 ◽  
pp. 204173142110042
Author(s):  
Rao Fu ◽  
Chuanqi Liu ◽  
Yuxin Yan ◽  
Qingfeng Li ◽  
Ru-Lin Huang

Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.



2012 ◽  
Vol 6 (1) ◽  
pp. 449-457 ◽  
Author(s):  
KL Chan ◽  
CC Mok

Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty.





2021 ◽  
Author(s):  
Kazuya Kaneda ◽  
Kengo Harato ◽  
Satoshi Oki ◽  
Yoshitake Yamada ◽  
Masaya Nakamura ◽  
...  

Abstract Background The classification of knee osteoarthritis is an essential clinical issue, particularly in terms of diagnosing early knee osteoarthritis. However, the evaluation of three-dimensional limb alignment on two-dimensional radiographs is limited. This study evaluated the three-dimensional changes induced by weight-bearing in the alignments of lower limbs at various stages of knee osteoarthritis.Methods 45 knees of 25 patients (69.9 ± 8.9 years) with knee OA were examined in the study. CT images of the entire leg were obtained in the supine and standing positions using conventional CT and 320 low-detector upright CT, respectively. Next, the differences in the three-dimensional alignment of the entire leg in the supine and standing positions were obtained using 3D-3D surface registration technique, and those were compared for each Kellgren–Lawrence grade. Results Increased flexion, adduction, and tibial internal rotation were observed in the standing position, as opposed to the supine position. Kellgren–Lawrence grades 1 and 4 showed significant differences in flexion, adduction, and tibial internal rotation between two postures. Grades 2 and 4 showed significant differences in adduction, while grades 1 and 2, and 1 and 3 showed significant differences in tibial internal rotation between standing and supine positions.Conclusions Weight-bearing increased the three-dimensional deformities in knees with osteoarthritis. Particularly, increased tibial internal rotation was observed in patients with grades 2 and 3 compared to those with grade 1. The increase in tibial internal rotation due to weight-bearing is a key pathologic feature to detect early osteoarthritic change in knees undergoing osteoarthritis.



2020 ◽  
Vol 21 (19) ◽  
pp. 7233
Author(s):  
Sébastien Pigeot ◽  
Paul Emile Bourgine ◽  
Jaquiery Claude ◽  
Celeste Scotti ◽  
Adam Papadimitropoulos ◽  
...  

Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, leading to ectopic bone formation. In this study, we aimed at engineering and devitalizing upscaled quantities of HyC ECM within a perfusion bioreactor, followed by in vivo assessment in an orthotopic bone repair model. We hypothesized that the devitalized HyC ECM would outperform a clinical product currently used for bone reconstructive surgery. Human MSC were genetically engineered with a gene cassette enabling apoptosis induction upon addition of an adjuvant. Engineered hMSC were seeded, differentiated, and devitalized within a perfusion bioreactor. The resulting HyC ECM was subsequently implanted in a 10-mm rabbit calvarial defect model, with processed human bone (Maxgraft®) as control. Human MSC cultured in the perfusion bioreactor generated a homogenous HyC ECM and were efficiently induced towards apoptosis. Following six weeks of in vivo implantation, microcomputed tomography and histological analyses of the defects revealed an increased bone formation in the defects filled with HyC ECM as compared to Maxgraft®. This work demonstrates the suitability of engineered devitalized HyC ECM as a bone substitute material, with a performance superior to a state-of-the-art commercial graft. Streamlined generation of the devitalized tissue transplant within a perfusion bioreactor is relevant towards standardized and automated manufacturing of a clinical product.



PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0178781 ◽  
Author(s):  
Chen-he Zhou ◽  
Jia-hong Meng ◽  
Chen-chen Zhao ◽  
Chen-yi Ye ◽  
Han-xiao Zhu ◽  
...  


Author(s):  
Shal N

This review presents the recent advances and the current state-of-the-art of bioactive glass-based hybrid biomaterials for bone regeneration. Hybrid materials comprise two (or more) constituents at the nanometre scale, in which typically, one constituent is organic and functions as the matrix phase and the other constituent is inorganic and behaves as the filler phase. Such materials, thereby, more closely resemble natural bio-nanocomposites such as bone. Various glass compositions in combination with a wide range of natural and synthetic polymers have been evaluated in vivo under experimental conditions ranging from unloaded critical-sized defects to mechanically-loaded, weight-bearing sites with highly favourable outcomes. Additional possibilities include controlled release of anti-osteoporotic drugs, ions, antibiotics, pro-angiogenic substances and pro-osteogenic substances. Histological and morphological evaluations suggest the formation of new, highly vascularised bone that displays signs of remodelling over time. With the possibility to tailor the mechanical and chemical properties through careful selection of individual components, as well as the overall geometry (from mesoporous particles and micro-/nanospheres to 3D scaffolds and coatings) through innovative manufacturing processes, such biomaterials present exciting new avenues for bone repair and regeneration.



1989 ◽  
Vol 109 (5) ◽  
pp. 2537-2545 ◽  
Author(s):  
P Bruckner ◽  
I Hörler ◽  
M Mendler ◽  
Y Houze ◽  
K H Winterhalter ◽  
...  

Primary chondrocytes from whole chick embryo sterna can be maintained in suspension culture stabilized with agarose for extended periods of time. In the absence of FBS, the cells remain viable only when seeded at high densities. They do not proliferate at a high rate but they deposit extracellular matrix with fibrils resembling those of authentic embryonic cartilage in their appearance and collagen composition. The cells exhibit many morphological and biochemical characteristics of resting chondrocytes and they do not produce collagen X, a marker for hypertrophic cartilage undergoing endochondral ossification. At low density, cells survive in culture without FBS when the media are conditioned by chondrocytes grown at high density. Thus, resting cartilage cells in agarose cultures can produce factors required for their own viability. Addition of FBS to the culture media leads to profound changes in the phenotype of chondrocytes seeded at low density. Cells form colonies at a high rate and assume properties of hypertrophic cells, including the synthesis of collagen X. They extensively deposit extracellular matrix resembling more closely that of adult rather than embryonic cartilage.



2005 ◽  
Vol 85 (2) ◽  
pp. 159-168 ◽  
Author(s):  
David A Brown ◽  
Sabina Nagpal ◽  
Sam Chi

Abstract Background and Purpose. This case report describes implementation of a limb-loaded cycling (LLC) training program as a feasible exercise for people in early phases of locomotor training following stroke. Case Description. Two individuals with early-stage poststroke hemiplegia participated in the LLC program as an adjunct to physical therapy intervention. Performance of LLC involved cycling while supporting progressive amounts of applied load and weight shifting from one lower extremity to the other lower extremity. The LLC was conducted daily during 2 to 3 weeks of inpatient rehabilitation. Outcomes. The LLC progressed with increases in weight bearing and force generation, as evidenced by larger amounts of limb loading during pedaling. The patients tolerated all loads without cardiorespiratory distress. Discussion. Limb-loaded cycling can accommodate people with little force-generating capability or weight-bearing ability as they practice locomotor skills. Gains in locomotor ability may be aided by the addition of this exercise regimen to patients' daily physical therapy.



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