Monday, April 4, 2011

interstitial growth

Since we're trying to induce interstitial growth with LSJL ala endochondral ossification.  It's important to understand how it works.

Mixture theory-based poroelasticity as a model of interstitial tissue growth.

"the mixture model [for interestitial tissue growth] admits the possibility of following many solid and fluid constituents and it admits the possibility of having chemical reactions occurring"

"A mixture is a material with two or more ingredients, the particles of which are separable, independent, and uncompounded with each other. If the distinct phases of a mixture retain their identity, the mixture is said to be immiscible; if they lose their identity, the mixture is said to be miscible."

"Poroelasticity is atheory that models the interaction of deformation and fluid flow in a fluid-saturated porous, elastic medium. The deformation of the medium influences the flow of the fluid and vice versa."<-LSJL involves deformation and fluid flow in the medium.

"Interstitial flow is slow through a particular tissue because it is 8 liters per day or 5.55 cubic centimeters per minute for the entire human body "

"measurements in limb tissue have suggested they are on the order of 0.1–2 microns per second (.03–.57 feet per day)"

"Deformation-driven interstitial flows, such as those that occur in bone tissue, are greater, on the order of tens of microns per second"

The influence of function on chondrogenesis at the epiphyseal cartilage of a growing long bone.

"In order to study the behaviour of epiphyseal cartilage in a nonfunctional environment, the third metacarpal bone was transplanted intracerebrally{the bone was transplanted into the brain} as an isograft between 7-day-old litter-mate rats. Host animals were killed 1, 2, 3, 4, 5, 6 weeks post-operatively, and the cellular kinetics evaluated by means of tritiated thymidine autoradiography. The study was also used to compare the effects of function on chondrogenesis at the epiphyseal cartilage with that previously demonstrated for the condylar cartilage of the mandible. Transplantation resulted in three major changes in the cartilage; there was a decreased rate of proliferative activity in the cell columns; the cartilage failed to maintain a satisfactory increase in transverse diameter; the cells of the perichondrium differentiated into osteoblasts instead of chondroblasts. Autoradiographic and histological findings suggested that the inability of the cartilage to increase in transverse diameter was related to the decreased rate of proliferative activity in the cell columns and not to the cessation of perichondrial chondrogenesis. On the basis of these findings two conclusions can be made. 1. Extrinsic mechanical stresses associated with function appear to be necessary for the normal interstitial growth of epiphyseal cartilage during postnatal development, suggesting that functional activity can influence the rate of cell proliferation. 2. Functional activity provides the stimulus for the differentiation of perichondrial cells into chondroblasts."

"Normally the edges of the epiphyseal cartilage plate, in addition to being continuous with the cartilage of the rest of the epiphysis gradually blend into the tissues comprising the perichondrium. In the transplants however the edges of the cartilage terminated abruptly"

"Transplanted long bones are capable of achieving longitudinal growth levels comparable to those of the bone in situ, the cell columns continued to divide at rates that were sufficient to account for length increments approaching normal levels, but insufficient to provide the additional columns necessary to maintain a normal increase in transverse diameter."

"Epiphyseal cartilage increases in transverse diameter by interstitial growth"

"Osteogenesis requires a higher level of vascularity than chondrogenesis"<-cartilage is hypoxic and has an inhibitory effect on vascularity.

"The common initiating factors in evoking either osteogenesis or chondrogenesis, are the degree of vascularity of the tissues and the presence or absence of mechanical stresses."<-if vascularity does support osteogenesis over chondrogenesis then it is surprising that chondrogenesis occurs in limb lengthening where vascular factors are highly upregulated.

Zone-Specific Micromechanical Properties of the Extracellular Matrices of Growth Plate Cartilage

"The average elastic modulus upon transverse indentation orthogonal to the long axis of the growth plate showed a gradient distribution, increasing significantly from the reserve zone (0.57 +/- 0.05 MPa) to mineralizing zone (1.41 +/- 0.19 MPa). Longitudinal indentation of the reserve zone along the long axis of the growth plate revealed an average elastic modulus of 0.77 +/- 0.12 MPa, significantly different from the same zone upon transverse indentation."

Maybe this pressure gradient is part of the way endochondral ossification increases height.

"[The growth plate has] the primary purpose of rapid interstitial growth while under large mechanical stresses"

"Longitudinal indentation of the primary spongiosa[spongy, trabecular bone] disclosed an average elastic modulus of 9.68 +/- 0.68 MPa."

"Different cellular zones of growth plate cartilage have differential expression of proteoglycans such as aggrecan, versican, decorin, biglycan, fibromodulin and lumican"

Comparison of Amounts and Properties of Collagen and Proteoglycans in Condylar, Costal and Nasal Cartilages

"Collagen does not only provide tensile strength, but counteracts forces responsible for interstitial growth such as osmotic pressure"<-Thus maybe we need to degrade cartilage to grow taller?

"Decreases in sizes and changes in structural compositions of proteoglycans occur with age"

"Incubation with exogenous hyaluronic acid, for reaggregation, and chromatography of the A1 fractions, intensive aggregate formation was seen in nasal cartilage"<-you can take exogenous hyaluronic acid.

"The chondroitin sulfate content of fraction A1 remained fairly similar in condylar cartilage but increased markedly in costal cartilage, and most markedly in nasal cartilage from age 25 days to age 35 days. Total amounts of aggregating proteoglycans and their sizes increased in condylar and costal cartilages with age. In nasal cartilage, amounts of aggregating proteoglycans also increased throughout"

"The role of collagen may be to counteract forces of high amounts of proteoglycans responsible for interstitial growth"

"Matrix synthesis increases mass and volume via swelling pressure as a result of osmotic pressure"

"the amount of proteoglycans is greater in cartilages, which have greater independent growth potential"<-thus by increasing the amount of proteoglycans we may be able to increase the amount of growth potential.

"Immature bovine articular cartilage explants from the superficial and middle layers were analyzed immediately or after incubation in serum-supplemented medium for 13 days. Other explants were treated with chondroitinase ABC to deplete tissue GAG and also either analyzed immediately or after incubation in serum-supplemented medium for 13 days.
Incubation in serum-supplemented medium resulted in expansive growth with a marked increase in tissue volume that was associated with a diminution of tensile integrity. In contrast, chondroitinase ABC treatment on day 0 led to a marked reduction of GAG content and enhancement of tensile integrity, and subsequent incubation led to maturational growth with minimal changes in tissue volume and maintenance of tensile integrity at the enhanced levels."

Thus interstitial growth may be mostly related to GAGs.

"Fetal and postnatal growth of the articular cartilage normally involves a net deposition of collagen that is greater than that of proteoglycan, as well as an increase in mechanical integrity. During maturation of articular cartilage from fetus to skeletal maturity, there is an increase in collagen and pyridinoline (Pyr) crosslink densities, but little or no change in the content of glycosaminoglycans (GAGs)"

"The content of water did not vary with chondroitinase ABC treatment and culture duration in the middle layer, but an interactive effect was observed in the superficial layer. Treatment with chondroitinase ABC did not affect water content on day 0, but during subsequent incubation of these explants it decreased slightly (2%). The content of water of the untreated explants of the superficial layer did not change during culture, and on day 13 was slightly higher (by 2%) than that in the superficial layer of the chondroitinase ABC–treated explants."

"The extent of volumetric growth was generally paralleled by variations in the tissue contents of GAG and collagen, but not in the tissue content of Pyr. In each layer, GAG content (GAG/WWi) was reduced by chondroitinase ABC treatment and increased during culture, with an interactive effect"

"chondroitinase ABC–treated and subsequently cultured explants were able to restore GAG content to native levels"<-maybe similarly the cartilage is able to restore GAG content from exogenously high levels.

"demonstrated the ability of cartilage to restore proteoglycan content and organization within 4–10 days after enzymatic digestion by increasing the rate of proteoglycan synthesis"<-Thus maybe you should cycle off of proteoglycans once every four days if this return to equilibrium is similar with exogenously high levels.

A study from 1931, LINES OF ARRESTED GROWTH IN THE LONG BONES IN CHILDHOOD: THE CORRELATION OF HISTOLOGICAL AND RADIOGRAPHIC APPEARANCES IN CLINICAL AND EXPERIMENTAL CONDITIONS, has an interesting theory "there is no interstitial growth in length in the shaft of the tibia, and all growth in length takes place by the apposition of new bone to the ends of the diaphysis at the growth cartilages"

If we consider the epiphysis and diaphysis to be two different parts this is true.

Interstitial growth may occur within cartilage but not in bone efficiently which is why cartilage can make you taller but bone only has limited ability.

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