Developmental Biology I: Bone Development, Repair, and Regeneration

2019 ◽  
Author(s):  
Mimi R. Borrelli ◽  
Ledibabari M. Ngaage ◽  
Derrick C. Wan ◽  
Michael T. Longaker ◽  
H. Peter Lorenz
Keyword(s):  
Stem Cell ◽  
Distraction Osteogenesis ◽  
Endochondral Ossification ◽  
Cell Function ◽  
Bone Development ◽  
Fracture Repair ◽  
Appendicular Skeleton ◽  
Craniofacial Skeleton ◽  
Biology I ◽  
Skeletal Stem Cell

Defects of the skeletal system are extremely common and amount to a significant biomedical burden. Bone is a unique tissue that retains its regenerative potential into adulthood. The biology behind bone development, repair, and regeneration is thus of considerable interest, and may lead to advances in patient care. There are two distinct forms of osteogenesis; bones of the craniofacial skeleton develop via intramembranous ossification, whilst bones of the appendicular skeleton form by endochondral ossification. In this review, bone regenerative mechanisms based on skeletal stem cell function during fracture repair and during distraction osteogenesis are reviewed.  Skeletal stem cell function more closely follows developmental mechanisms during distraction osteogenesis compared to fracture osteogenesis.  This review contains 5 figures and 50 references. Keywords: skeletal stem cell, osteogenesis, skeletogenesis, mechanotransduction, regeneration, remodeling, focal adhesion kinase, ossification

Cell Intrinsic versus Extrinsic Factors and their Role in Skeletal Stem Cell Function with Aging

2014 ◽  
Vol 186 (2) ◽  
pp. 689
Author(s):  
A. McArdle ◽  
C.K. Chan ◽  
D.D. Lo ◽  
M.T. Chung ◽  
K. Senarath-Yapa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Extrinsic Factors ◽  
Skeletal Stem Cell

scholarly journals Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair

2019 ◽  
Author(s):  
S. Herberg ◽  
A. M. McDermott ◽  
P. N. Dang ◽  
D. S. Alt ◽  
R. Tang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Formation ◽  
Mechanical Loading ◽  
Endochondral Ossification ◽  
Bone Development ◽  
Human Mesenchymal Stem Cell ◽  
Bone Defects ◽  
Mechanical Environment ◽  
Tgf Β1

AbstractEndochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation and is directed by local morphogen signals and mechanical cues. Here, we aimed to mimic these developmental conditions for regeneration of large bone defects. We hypothesized that engineered human mesenchymal stem cell (hMSC) condensations with in situ presentation of transforming growth factor-β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles would promote endochondral regeneration of critical-sized rat femoral bone defects in a manner dependent on the in vivo mechanical environment. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with dual BMP-2 + TGF-β1 fully restoring mechanical bone function by week 12. In vivo ambulatory mechanical loading, initiated at week 4 by delayed unlocking of compliant fixation plates, significantly enhanced the bone formation rate in the four weeks after load initiation in the dual morphogen group. In vitro, local presentation of either BMP-2 alone or BMP-2 + TGF-β1 initiated endochondral lineage commitment of mesenchymal condensations, inducing both chondrogenic and osteogenic gene expression through SMAD3 and SMAD5 signaling. In vivo, however, endochondral cartilage formation was evident only in the BMP-2 + TGF-β1 group and was enhanced by mechanical loading. The degree of bone formation was comparable to BMP-2 soaked on collagen but without the ectopic bone formation that limits the clinical efficacy of BMP-2/collagen. In contrast, mechanical loading had no effect on autograft-mediated repair. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.One Sentence SummaryMimicking aspects of the cellular, biochemical, and mechanical environment during early limb development, chondrogenically-primed human mesenchymal stem cell condensations promoted functional healing of critical-sized femoral defects via endochondral ossification, and healing rate and extent was a function of the in vivo mechanical environment.

The osteoarthritic niche and modulation of skeletal stem cell function for regenerative medicine

2012 ◽  
Vol 7 (8) ◽  
pp. 589-608 ◽  
Author(s):  
E. L. Williams ◽  
C. J. Edwards ◽  
C. Cooper ◽  
R. O. C. Oreffo
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Function ◽  
Skeletal Stem Cell

Distraction Osteogenesis in the Treatment of Craniofacial Anomalies: Applications and Outcomes

2020 ◽  
Vol 5 (6) ◽  
pp. 1469-1481 ◽  
Author(s):  
Joseph A. Napoli ◽  
Carrie E. Zimmerman ◽  
Linda D. Vallino
Keyword(s):  
Distraction Osteogenesis ◽  
Bone Growth ◽  
Upper Airway ◽  
Craniofacial Anomalies ◽  
Craniofacial Skeleton ◽  
Facial Skeleton ◽  
Psychosocial Impairment ◽  
And Function ◽  
Correct Structure

Purpose Craniofacial anomalies (CFA) often result in growth abnormalities of the facial skeleton adversely affecting function and appearance. The functional problems caused by the structural anomalies include upper airway obstruction, speech abnormalities, feeding difficulty, hearing deficits, dental/occlusal defects, and cognitive and psychosocial impairment. Managing disorders of the craniofacial skeleton has been improved by the technique known as distraction osteogenesis (DO). In DO, new bone growth is stimulated allowing bones to be lengthened without need for bone graft. The purpose of this clinical focus article is to describe the technique and clinical applications and outcomes of DO in CFA. Conclusion Distraction can be applied to various regions of the craniofacial skeleton to correct structure and function. The benefits of this procedure include improved airway, feeding, occlusion, speech, and appearance, resulting in a better quality of life for patients with CFA.

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