>>67
The strength of collagen is regulated by cross-linked structures inter-locking adjacent molecules.
Then, collagen-molecules secreted from osteo-blasts are regularly ordered.
Next, adjacent collagen-molecules coupling through each cross-link are stabilized.
There are two kinds of cross-links.
一
>>68
One is called good-natured enzyme-dependent cross-link ( immature or mature cross-link ), this plays role to regularly place molecules and strengthens bone with moderate elasticity.
By the way, immature or mature cross-link is called 'physiological cross-link' .
Such cross-links are orderedly formed through actions of enzymes called lysyl oxidase generated from osteoblasts.
Furthermore, these cross-links give influence on calcification.
一
>>69
Meanwhile, under an AGEs-cross link ( aging or bad-natured cross link ), collagen-molecules are over-tied at random, the organization itself loses flexibility, elasticity and consequently it becomes easier to be broken.
Pentosidine is a representative cross link of AGEs.
As this matter has a positive correlation with the total quantity of AGEs , it's generically utilized as a surrogate marker to catch the total quantity.
一
>>70
2. Relations of changes of osteo-collagens into AGEs with microscopic bone-fractures
Saito found out that bone-fracture at micro scale as a main factor to lower the strength of bone is caused by over-formations of AGEs-cross links among collagen-molecules.
To understand inter-relations which hold among such factors to determine osteo-quality, it's convenient to liken bone to reinforced concrete.
As we know, cracks found out on an outer wall made of reinforced concrete are originated in exhaustions of those reinforcing bars due to aging.
In this case, micro-damages correspond to cracks on a reinforced concrete.
一
>>71
3. Changes of osteo-collagens into AGEs with aging
Saito analyzed influences of aging on formations of collagen-bridges in human bones ( 0 〜 84 in age ).
Especially, proximal humerus, distal radius, ilium, femoral neck, fourth lumbar vertebral body and the middle of tibia are known as parts easy to cause fracture due to osteoporosis.
Collagens were extracted from these respective parts, pentosidines ( AGEs-cross links ) contained in them were quantified and the number of cross links per collagen-molecules was calculated out.
一
>>72
So that, it's found out that pentosidines increase with aging over all taken parts.
The quantity of pentosidines in not only blood but also urine increases with aging in proportion to such variations.
Besides, the increase of AGEs in bones with aging are found out independently of gender.
一
一
>>73
4. Bone-matrix marker ; pentosidine and homocystein
Saito and others performed bone-biopsies ( cortical bone, cancellous bone ) on primary osteoporosis victims who had received femoral neck fractures ( 15 〜 25 cases ) and analyzed extracted collagens.
As the result, it has been made clear that AGEs-cross links namely pentosidines are over-formed even in young osteo-domains in early stages of calcification in cases of fracture.
Many supplementary examinations have made clear that over-formations of AGEs namely pentosidines in osteo-collagen directly cause the fall in strength of bone.
一
>>74
It's known that pentosidines contained in urine at high value have positive correlation with changes of osteo-collagens into AGEs .
Furthermore, cooperative researches with Shiraki and others have shown that these pentosidines at high value can be regarded as a factor to represent the risk of fracture independently of osteo-density.
一
>>75
The same investigation as that to know the risk of new generation of vertebral fracture were executed over uncured 432 women at postmenopause.
So that, especially, a group at maximum quartile value of pentosidines contained in urine ( 47.5 pM/mgCr , on compensations with creatinine ) has the risk of fracture independently of osteo-density, existing fractures, age and renal function.
※ maximum quartile value ;
gathered data are divided into four groups in order of size of value, the maximum group of those four groups.
一
>>76
Furthermore, according to some researches of symptom on contrast, if pentosidines are contained in osteo-collagen of a person at high value, homocysteines contained in blood of the person also are at high value.
Significantly, it has been successively reported that hyperhomocysteinemia is not only a risky factor to cause hardening of the arteries but also the risk of fracture independent of osteo-density in general people.
一
>>77
Then, to check whether hyper-homocysteinemia excessively induces variations of osteo-collagens into AGEs or not, we made tests on rabbits from which ovaries are eliminated ( but they had same remodeled bones as human bones ).
So that, it has been found out that if hyper-homocysteinemia is caused, pentosidines are excessively generated in osteo-collagen and changes of osteo-collagens into AGEs are promoted.
一
>>78
Furthermore, it also has been made clear that the strength of bone is weakened without fall in osteo-density due to this process.
Namely, it's probable that homocysteines in blood at high value promote changes of osteo-collagens into AGEs and increase the risk of fracture.
OFELY study showed that the risk of fracture rises in a group containing pentosidines in urine at high value too.
一
>>79
And, Saito & others found out that the group of the patients who show the brittleness of bone is classified into following three types on osteo-density and osteo-quality according to vertical investigations in age over 502 women at postmenopause ( Nagano-cohort ).
一
>>80
① Low osteo-density type ;
This type is 3.6 times higher than the cases at YAM ＞ 80 % in risk of fracture.
※ YAM ;
The abbreviation of Young Adult Mean. Namely, a mean of young generations in osteo-density.
② Osseous deterioration type ;
This type is 3.6 times higher than the cases at YAM ＞ 80 % in risk of fracture.
③ ① ＋ ② ;
This type is 7.2 times higher than the cases at YAM ＞ 80 % in risk of fracture.
In this case, the rate among respective types in number in Nagano cohort was as follows.
① : ② : ③ ＝ 5 : 3 : 2
Namely, it was made clear that the appearance of osseous deterioration type is not necessarily rare.
Homocysteines in blood at high value ( ＞ 13 nmol/mL ) and pentosidines in urine at high value ( ＞ 47 pmol/mg creatinine ) are useful as surrogate markers to find out symptoms of such osseous deteriorative osteoporosis.
>>81
It's possible to request measurements of homocysteines in blood and pentosidines in blood or in urine of contractors for inspection.
However, in Japan at present ( 2013 ), we can't apply the health insurance to such measurements on osteoporosis.
一
>>82
Furthermore, according to vertical studies in age over 251 osteoporotic patients at postmenopause,
it has been made clear that in cases of ③ low osteo-density ＋ osseous deterioration type osteoporosis, even if osteo-densities were raised with bisphosphonate ( a kind of bone-absorption suppressive drug ), the risk of fracture was 'not' reduced.
These facts mean that we must primarily suppress variations of bone collagens into AGEs to sufficiently improve the strength of bone.
一
>>83
5. Changes of bone-collagens into AGEs with diabetes and fall in renal function
In the case of II-type diabetes, hardening of the arteries often appears as a complication.
According to meta-analyses, it has been made clear that a fracture of bone can be caused even at high osteo-density.
So, it's supposed that fractures are actually originated in osseous deterioration.
And, Saito & others made clear the following mechanism on observations of rats which naturally received diabetes.
Low vitamin B6-state ( a state containing vitamin B6 at low value ) and remarkable durable hyper-glycemia originated in the failure of action of insulin bring over-formations of pentosidines in osteo-collagen,
consequently they cause the fall in the strength of bone without lowering the osteo-density.
一
>>84
In the case of II-type diabetes, pentosidines contained in blood or urine at high value also can be regarded as a risk of fracture independent of other some factors.
This is a considerable example to show the correlation between the increase of pentosidines in bone-collagen and the fall in the strength of bone.
一
>>85
Furthermore, Saito & others made clear that renal functional failure not only increases oxidative stress, carbonyl stress but also promotes variations of osteo-collagens into AGEs.
Besides, they drew it from bone biopsies over cases with renal failure that variations of osteo-collagen into AGEs bring falls in functions as osteo-blasts ( namely, fall in function to form bone ).
一
>>86
6. Limits of models with rodents ( such as rat, mouse ) in estimating changes of bone into AGEs
It's difficult to find out a significant increase of AGEs in an osseous substance of a rodent with short life span on aging and pathological models.
Though AGEs increase under remarkable high blood sugar even in the case of rodent, the increase is very small in comparison with that in a human osseous tissue.
We must execute tests on larger-sized animals with longer life span ( rabbit, dog, monkey, etc ) to obtain more reliable estimations.
Therefore, as human being is same as rodent in formation of enzyme-dependent cross-links, we perform experiments with rodents to estimate such formations.
一
>>87
Meanwhile, we plan a test on larger-sized animals for measurements of AGEs in osseous tissues, clarification of pathology and estimation of drug effect.
※ And, results drawn from human osseous tissue biopsies are compared with these data.
Furthermore, remodelings (≒ renewal of tissues namely metabolism ) are not carried out in bones of rodent.
Namely, those cases are different from cases of human being, as a single modeling is continued for a life span, it's not proper to analyze aging process of human bone with rodents.
一
>>88
・ Conclusion
Briefly explaining of osteoporosis, changes of osteo-collagen into AGEs are promoted by some factors ( ・ fall in osteo-density originated in the promotion of bone-remodeling, ・ fall in function of osteo-blast, ・ promoted oxidative stress ),
consequently osseous tissues are remarkably weakened.
Oxidative stress increases at menopause, variations of osseous tissues into AGEs are promoted without hyper-homocysteinemia.
In particular, as the cases at low osteo-density ＋ osseous deterioration have remarkable high risk of fracture, we must estimate markers related to osteo-density and osseous markers at the same time, choose an effective medicine which is suitable to the pathological type.
Furthermore, if the replacement with an artificial joint is performed on an osseous deterioration type osteoporotic case at high oxidative stress, as it's highly probable that a tissue-deterioration originated in the oxidation of polyethylene also is promoted,
we should take the use of medicines or chemicals with anti-oxidative actions into consideration too.
• High-polymer materials which are used as main bio-materials in the field of orthopedics
〈 Preface 〉
As the goal of regenerative medicine is to revive lost living functions, roles of bio-materials to help the purpose are still left.
1. Present conditions of materials to fix bones for treatment for fracture
Artificial materials with high strength are used to restore a fractured part and support the chest in respective fields such as orthopedics, oral surgery and thoracic surgery.
Primarily, plates and screws for joining bones should be used as supplementary tools to cure of fractures, they need to be removed as quickly as possible after recovery to prevent the weakening of bone.
>>90
At present, most of the clinical materials to fix bones are made of metal or ceramic.
But, elastic degrees of these materials are so high that they can deform bones.
And, metallic ions flowing out of those materials can injure the living body.
Accordingly, if those materials are same as bones in elastic degree and they are well resolved-absorbed into the living body, they are convenient to join bones.
一
>>91
So that, it also will be possible to cancel various bad influences caused by foreign matters which are left in a living body for a long term.
Researches to apply poly-lactic acid as a kind of possible high polymer to be resolved and absorbed into a living body to cure for fracture have a comparatively old history.
Gen and others developed materials made of PLLA ( PoLy-Lactic Acid ) to cure of fracture, those materials have been clinically utilized over the world ( the same as a surgery-assisting robot called da Vinci ).
一
>>92
Furthermore, the following way to mold was devised to improve its mechanical characters.
Once a tissue is molded with degradable & absorbable high-polymer materials in vivo containing hydroxyapatite such as PLLA, its strength and elastic degree are improved by uni-axially stretching the molded tissue.
Moreover, a poly-lactic acid rod processed with injection molding is uni-axially stretched at high temperature, high magnification ( 7 〜 12 times ), so that the fibrillated tissue gets higher strength and higher elastic degree.
一
>>93
Besides, Gen and others produced an other material to join bones by uni-axially stretching a fusion-molded body made of PLLA with viscous mean molecular mass of more than two hundred thousands.
But, in cases of above materials to fix bones, as only the initial strength and the hydrolysis-resistance (≒ durability against hydrolysis) are taken into consideration, those materials have been still in-sufficient in elastic degree, durability of strength in living body.
一
>>94
Especially, in-sufficiencies of following aspects have been pointed out.
・ Degradabilities and absorbabilities in vivo after the fracture is cured.
・ The promotion of degradabilities & absorbabilities in vivo after the degree to keep the initial strength gets 0 .
In general, a cure for fracture is completed for about 6 〜 8 months.
By the way, after the above material to cure of fracture is implanted into a living body, as the molecular mass is reduced, the strength also falls.
Accordingly, such a character is desirable for curing of fracture in some sense.
一
>>95
But, the initial strength gets 0 and the molecular mass also are reduced from two hundreds thousands to thousands 〜 tens of thousands within about 4 months after the implantation.
Furthermore, particle-like crystals are left in the living body for about 3 〜 5 years.
一
>>96
Therefore, even if these materials are applied to osteo-tissues, as speeds required to decompose and absorb them are so slow, the cavity of the bone is occupied with fibrous tissues, osseous tissues are not re-organized in a part into which a material to heal fracture is implanted even after 3 〜 5 years pass and the part will be left to be hollow.
Such a situation not only remarkably lowers the dynamical strength to bear a weight but also causes various following complications more seriously.
一
>>97
2. Present conditions of artificial joint ( 2013 )
Basic conditions necessary to materials for artificial joint are as follows.
① Exellent suitabilities for living body
② Sufficient dynamical strength
③ Excellent abrasion-resistant properties ( durabilities against abrasion )
④ Which are chemically stable without deteriorations of materials
Though artificial joints to satisfy above respective conditions are desired, actual situations have been still insufficient for such requirements.
一
>>98
Until now, metals have been mainly used as hard materials for artificial joint.
But, recently, ceramics also are partially being used for artificial joint.
Especially, alumina is preferred due to following properties.
・ Exellent suitabilities for living body and mechanical strength
・ This material has better affinity with Ultra High Molecular Weight PolyEthylene ( UHMWPE ) than metals in abrasive character.
But, as this alumina is fragile, zirconium is more expected as a stronger ceramic for artificial joint recently.
一
>>99
As stated in the above, various shaped artificial joints are clinically applied, they are synthesized by combining hard materials such as metals and ceramics with soft materials such as UHMWPE ( Ultra High Molecular Weight PolyEthylene ).
Then, osteo-cement plays a main role to fix an artificial joint in the bio-osseous tissue.
Osteo-cement is solidified by polymerizing methyl methacrylate in a living body.
Particularly, this osteo-cement has succeeded in strongly joining an artificial joint to a bionic bone.
一
>>100
However, osseous tissues around the osteo-cement get necrotic due to the heat of about 90 ℃ generated in polymerizing osteo-cement and residual monomers, fibrous tissues are formed instead of osseous tissues.
Therefore, after a long time passes from the implantation, the 'loosening' of the artificial joint is caused as the most serious complication.
一
>>101
Recently ( 2013 ), it has been found out that not only problems related to osteo-cement but also abrasions of UHMWPE ( Ultra High Molecular Weight PolyEthylene ) give remarkable influences on such the generation of 'loosening' .
There are many clinically applied cases except for representative artificial joints sold at present as shown in the above.
As those models also are constantly varied, those contents also will be further changed after several years.
一
>>102
More than 30 years have passed since artificial joints were developed and they were clinically applied to patients suffering from arthro-diseases.
For those some decades, many bed-ridden patients could walk again and return to society.
In the sense, artificial joints could considerably contribute to social welfare.
But, after about 10 〜 20 years, after 5 years at the earliest from an operation, the 'loosening' of artificial joint is caused as a complication at high frequency.
一
>>103
Consequently, as osseous tissues around the artificial joint are damaged, it's needed to execute a surgery again for healing the injury.
Such problems are being reported over the world, they are regarded as serious problems in the field of orthopedics.
一
>>104
Recently, some causes which bring damages to bone have been made clear.
According to those reports, it has been found out that as UHMWPE used as a material for rubbing parts of artificial joint is low in abrasion-resistance in comparison with cartilage, it's poor in stress-relaxation against impulsive weight.
一
>>105
Observing a Charnley type UHMWPE-socket with X-ray, it's abraded by about 0.08 mm every year.
Then, if one granule of UHMWPE-abrasion powders has a span of about 10 μm , 2800 abrasion granules are generated around the joint.
If the quantity of generated abrasion granules is small, as those granules can be digested by macrophages and foreign body giant cells, bad granulation tissues are not formed.
一
>>106
But, if large quantities of abrasion granules are generated, as even those cells can not digest generated granules, bad granulation tissues originated in remaining abrasion particles promote necrosis and osteo-injury.
So that, the patient not only gets impossible to walk again but also becomes suffered from intense agony.
一
>>107
As most of the 'loosenings' as the most serious complication for artificial joint are caused between bones and osteo-cements, artificial joints without osteo-cements had been developed and they have been clinically used since the 1980's .
To strongly fix this cementless artificial joint on the bone, we must modify the surface of the material so as to be porous and push newly generated osseous tissues into those modified materials.
一
>>108
For that, various ways including ways to coat the surface with active ceramics possible to directly join to bones such as hydroxyapatite, methods to screw in and methods to spike, etc are being executed.
But, recently, we have found out that even if these cementless artificial joints are applied to injured parts, the generation of 'loosenings' is not reduced, rather the bone-absorption around an implanted part becomes remarkable.
一
>>109
And, it has been reported that large quantities of UHMWPE-abrasion granules are contained in tissues around the implanted part, granulation tissues surrounded by macrophages and foreign body giant cells absorb osseous tissues near those implanted parts, consequently osseous tissues decay.
一
>>110
In an international meeting of orthopedics held in September of 1993 , Harris.W bundled up these problems into a concept called 'particle disease' , it was made clear that the most serious problems related to artificial joint at present are originated in abrasion-resistances of UHMWPE .
Since then, problems of UHMWPE-abrasion have been actively dealt with in meetings of orthopedics and bio-material.
However, these problems have never been solved yet ( 2013 ) .
一
>>111
・ Present conditions of cartilage for artificial joint ( 2013 )
Bio-joint ( namely a joint in a living body ) functionally relaxes an extreme impulsive weight, uniformly conducts such a weight to bones under cartilages and is durable against abrasion for about 80 years under very low friction.
一
>>112
Fluid membranes between articular cartilage and the surface of joint, cancellous bones under cartilages contribute to supporting amazing high performances of bio-joint.
However, it also is sure that functions of joint are gradually lowered due to aging, people who suffer from articular diseases such as deformable hip osteo-arthrists increase.
一
>>113
Therefore, it's not rare to reluctantly replace a bio-joint with an artificial joint for recovering lost functions.
In the case of most popularly used artificial hip joint at hip joint at present, a metallic stem such as titanium alloy is inserted into its thighbone-side directly or through osteo-cement, meanwhile a high-polymer hard material such as UHMWPE-cup is combined with its ace tabular side.
一
>>114
Correction ;
Therefore, it's not rare to reluctantly replace a bio-joint ( living joint ) with an artificial joint for recovering lost functions.
In the case of most popularly used artificial hip joint
at present ( 2013 ), a metallic stem such as titanium alloy is inserted into its thighbone-side directly or through osteo-cements, meanwhile a high-polymer hard material such as UHMWPE-cup is combined with its acetabular side.
一
>>115
But, after a replacement surgery, large quantities of polyethylene abrasion granules are generated between a stem and a cup, besides 'loosenings' originated in osteo-cements and surrounding granulation tissues are caused at very high frequency.
Therefore, in many cases, a secondary replacement is needed within 10 〜 20 years after the surgery. Furthermore, as it's needed to eliminate remarkable quantities of osseous tissues including healthy bones in surgery, considerable loads are brought to the patient.
一
>>116
Then, as considerable quantities of osseous tissues have been already lost in secondary surgery, these problems make such surgeries troublesome.
Accordingly, artificial joints are applied to only aged persons at present.
一
>>117
By the way, in the case of deforming coxarthropathy ( deforming hip osteo-arthritis ), as its focuses are found out in only partial domains of the surface of joint, we don't have to remove the major part of cartilaginous cancellous trabecular bone group including healthy osseous tissues in performing a surgery.
一
>>118
Then, we should develop a surfacial replacement-type artificial articular cartilage to replace only the focus with an artificial material.
In some experiment, an artificial articular cartilage made of polyvinyl alcohol ( PVA ) was applied to a beagle dog.
In this case, a focus originated in femoral head necrosis was replaced with an artificial articular cartilage made of PVA , since then good conditions have been brought to the dog.
一
>>119
・ Present conditions of artificial inter-vertebral disk
Main dynamical ( or mechanical ) functions of vertebra are summarized into following three factors.
1. Protections of the spinal cord and nervous components
2. The support of the weight of a body trunk
3. Smooth motions of a body trunk
Namely, bearability and movability are mainly requested of this part.
一
>>121
To heal damages on inter-vertebral disk as a main cause of backache, a surgery to remove inter-vertebral disk and an operation to fix lumbar vertebra are mainly performed.
Especially, the latter treatment is frequently executed owing to improvements in instrument, conditions after the operation also comparatively become stable.
一
>>121
But, movability is partially lost due to the operation to fix vertebra.
Consequently, as extreme stresses are brought to non-fixed neighboring inter-vertebral disks, we must take bad influences into consideration.
It's desirable to develop artificial inter-vertebral disks for giving both bearability and movability with no pains to an injured vertebra again.
Provisionally, developments of artificial inter-vertebral disk have been being carried out for 30 years until now.
一
>>122
But, most of them are conceptual researches on biomechanics of vertebra.
Namely, though there are many theoretical reports to show dynamical characters required of artificial inter-vertebral disk and to propose new inter-vertebral materials, we can't find out cases in which such ideas were actually applied to a living body so much.
一
>>123
In most of the artificial inter-vertebral disks used until now, a material like polyethylene is inserted between metallic plates.
Failures originated in dislocations and deviations from regular positions have been reported until now.
一
>>124
In particular, if an artificial inter-vertebral disk deviates or is dislocated from the vertebral body,
as serious complications are caused, goals to develop artificial inter-vertebral disks are focused on following two points, namely,
( 1 ) the stable settlement of the part on the vertebral body
( 2 ) the physiological movabilities of the implanted inter-vertebral disk
一
>>125
An artificial inter-vertebral disk made of PVA which had been developed by Gen & others was implanted into the vertebral body of a beagle dog.
The condition after one year from the surgery was good.
一
>>125
• Present conditions of artificial ligament
Damages in ligaments of knee are frequently found out in athletes and sportspersons.
Recently, as the population of sportspersons increases, cases which receive such a damage also gradually increase.
一
>>127
In general, as damages in ligaments of knee especially damages in anterior cruciate ligament are not naturally healed, it's needed to perform a surgical operation for healing such an injury.
If such damages are left, serious troubles can be caused in not only returns to sports but also daily life.
In general, 〈 suture ＋ the transplantation of own tendon into the injured part 〉is performed to heal this damage.
一
>>128
But, complications originated in picking own tendon such as fall in muscular strength, pains and nervous paralyses are caused, consequently, a long time is required to return to sports, the decline in performance also is inevitable.
In the past, some types of artificial ligaments made of non-absorbent polyester had been produced.
But, stable effects have never been realized yet because of rejections in a living body and in-durability against stress for a long term.
一
>>129
Progresses in regenerative medicine enable developments of various artificial organs.
For now, regenerative medical approaches for an injured ligament have been scarcely performed, as there are no effective treatments for this damage, it's one of the most urgent subjects.
A ligament is a tissue in which respective components are closely bound and this is a comparatively simple tissue of fibrous blasts and collagens.
一
>>130
However, this organ still includes many unknown points from viewpoints of molecular biology and systematic engineering.
Because, as each tissue itself is very tiny, it's difficult to separate it into cellular units, furthermore characters proper to cells constituting a ligament have never been made clear yet.
一
>>131
About one hundred and fifty thousand reconstructive surgeries for injured anterior cruciate ligament are performed a year in USA , about thirty 〜 fifty thousand reconstructive surgeries for it are performed a year in Japan.
It's probable that considerable numbers of cases including surgeries for ligaments except for anterior cruciate ligaments are executed.
Developments of new artificial ligaments combined with bio-activated matters will give remarkable influences on medical and industrial fields.
一
>>132
• Future Works
At present, there are various absorbent materials to heal fracture, they are clinically applied to respective situations.
Then, PDS ( Poly Dioxanone ), TMC ( Tri Methylene Carbonate ) or PDLLA ( Poly DL Lactic Acid ) are applied to parts at comparatively low strength.
Meanwhile, PLLA ( Poly L Lactic Acid ) is applied to parts at which high initial strength is required.
Furthermore, various ideas ( for example, introductions of molecular orientations and formations of composites ) are taken into consideration to improve such an initial strength.
一
>>133
By the way, materials to join bones for healing fracture at present are as follows.
To sustain the osteo-strength of more than 200 MPa for about 3 months,
for example, composites of poly-lactic acid, co-polymers of lactic acids and glycolic acids with hydroxyapatites are uni-axially stretched.
一
>>134
Then,
200 MPa ; the strength of human cortical bone against compression & bending
About 3 months ; the minimum term until a broken bone is naturally healed
Poly Lactic Acid, co-polymer of lactic acid and glycolic acid ; degradable and absorbable high-polymers in vivo
Hydroxyapatite ; this matter is excellent in affinity with osseous tissue , with molecular mass of more than one hundred thousand
一
>>135
But. as pointed out previously, the degree to maintain strength with initial strength and hydrolysis has been partially improved, however after four months from the implantation namely after the initial strength gets 0 , implanted materials are still left in the living body without completely being resolved and absorbed. From now, we must solve these problems.
一
>>136
〈 Artificial Joint 〉
Since the success in the Charnley-type artificial hip joint with UHMWPE ( Ultra High Molecular Weight PolyEthylene ), UHMWPE s have been applied to most of rubbing parts of artificial joints.
But, UHMWPE-abrasion-granules generated due to frictions and abrasions cause necroses and decays of tissues around an artificial joint, besides the 'loosening' of the artificial joint.
一
>>137
Accordingly, recently, improvements in abrasion-resistance in UHMWPE (＝ durability against abrasion ) is strongly requested.
Though this improvement in abrasion-resistance is the most important subject for artificial joint, ways to improve those troubles have been scarcely found out.
At present, we are being urged to overcome this trouble.
一
>>138
〈 Artificial Articular Cartilage 〉
An artificial articular cartilage can be applied to an injured part comparatively early, besides, it's possible to apply it to the young generation and to keep various healthy functions with it.
For example, PVA ( Poly-Vinyl Alcohol )-hydrogel has been studied as a main material composing an artificial articular cartilage.
As this material contains waters, it has lubricative effects similar to those of living articular cartilage.
So, it's expected to keep a low frictional state with it.
一
>>139
Following two points are especially important to apply artificial articular cartilage to clinical fields.
(a) ways to settle it on the osteo-ground
(b) dynamical suitabilities including functionalities in wide sense
First, about (a), according to some researches, it has been made clear that if a titanium fiber mesh (＝ porous artificial bone) is used as a material to bond PVA-hydrogels to osseous tissues, newly generated bones get into respective holes of the TFM ( Titanium Fiber Mesh ), so that the adhesion of osseous tissues with TFMs is rigidly fixed.
一
>>140
And, if a PVA-solution at high concentration sufficiently permeates the TFM with injection molding method and the permeated solution is varied to a gel, a strong bond between PVA and TFM can be realized.
Namely, PVA-hydrogel can be regarded as a material for artificial articular cartilage which is very effective in the settlement of it on an osteo-ground.
Furthermore, this is very effective against the deterioration in vivo too.
Accordingly, we should advance researches of artificial articular cartilage on this material.
一
>>141
〈 Artifivial Inter-vertebral Disk 〉
The same as the case of artificial articular cartilage, Gen and others produced a material to settle an artificial inter-vertebral disk on a living vertebral body by pouring a PVA-solution into respective holes of TFM with an injection molding machine.
From now, we need to demonstrate the usefulness of the new type of artificial inter-vertebral disk through experiments in vivo and aim at clinical application of it.
一
>>142
〈 Artificial Ligament 〉
Followings are provisional aims in this field at present.
・ If mechanical stimuli and various cytokines are given to ligamental cells, reactions to those stimuli and supplies appear.
We need to establish ways to culture ligamental cells at higher cellular activated state on those reactions.
・ Polymers containing heparins with respective cytokine-bonding capacities are used to design matrices which enable cell-multiplication, vascular induction.
一
>>143
Furthermore, we need to prepare following materials to compose tissues with sufficient strength.
・ Collagen-gels to which dynamical stimuli such as periodic stresses and magnetic stimuli are given.
・ Hybrid artificial ligaments with which artificial high-polymers such as polylactic acid fibers and elastin-like protein-based polymers ※ are combined.
※ They were developed by Urry SR and others ( Queensland university of technology, Australia ) with genetic modification methods.
First, transplanting this artificial ligament into a rabbit, we must demonstrate that its functions are sustained.
一
>>144
• Achievemental levels of respective aims
It's desirable that materials introduced here are developed as medical high-polymer biomaterials which are gentle to living body.
Concretely, following researches should be supported.
〈 Materials to fix bones for healing fracture 〉
・ Developments of degradable & absorbable materials in vivo for fixing bones which are equal to metallic materials for fixing in reliability.
・ To raise initial elastic degrees of those materials to that of cortical bone.
・ After those initial strengths get 0 , they should be quickly degraded and absorbed into the living body.
一
>>145
〈 Artificial Joint 〉
As the replacement with an artificial joint brings remarkable stresses to the patient, we should develop an artificial joint which works for a long term of 30 〜 50 years with no troubles after the surgery.
〈 Artificial Articular Cartilage 〉
Artificial joints have considerably contributed to healing of deforming coxarthrosis.
But, as its durable spans are short ( 10 〜 20 years ), they are not suitable to patients at young generation.
And, we need to develop a surfacial replacement-type artificial articular cartilage which is clinically applicable to the replacement of a chondral surface.
一
>>146
〈 Artificial Inter-vertebral Disk 〉
Developments of artificial inter-vertebral disks which are similar to living inter-vertebral disks namely have both bearability and movability.
〈 Artificial Ligament 〉
Recent progresses of tissue-engineering and regenerative medicine have partially produced clinically applicable organs.
But, for now, regenerative medical fruits on ligament are scarcely found out.
Namely, there are limits in healing of injured ligament at the present medicine.
Accordingly, the establishment of ways to heal on tissue-engineering is urgent in this case ( in 2013 ).
一
• The waste disposal by thermo-plasma 〜 〈 1 〉
1. Preface
It's regarded that thermal plasma is useful to waste-disposal due to following characters.
1 ）As thermo-plasma is at high energy, high density and high temperature,
its speed for processing & reaction is quick.
2 ）Because of its high temperature, we can synthesize compositions at quasi-stable phase and in-equilibrium phase by properly quenching.
3 ）We can quickly start up & shut down the process because of conveying-heat at high speed on thermal plasma.
4 ）A small quantity of gas is sufficient to perform a processing by thermal plasma, so exaust gases can be kept at low quantity.
>>150
And, following processes are realized as practical uses for waste disposal.
Thermo-plasma is being used for large general waste disposal such as process to melt down burnt ash.
We can prevent heavy metals which are included in burnt ash issued from incinerators for urban garbages from melting and can turn them to be harmless by resolving dioxin through the thermo-plasma.
Besides, plasma-melting technology is practically used for medical waste disposal.
一
>>151
In such a system, wastes are thermally decomposed at anoxia condition, disused material carbides, hypodermic needles and phials, etc are turned to be stable slags by heating through plasma.
And, thermal plasma is being used to re-cycle dusts which are issued in great quantities from iron-manufacturing and steel-making factories too.
一
>>152
Dusts from an electric furnace are about equal to 1 〜 2 % of thrown raw materials, those dusts contain valuable metals such as Zn, Pb, Cr, etc.
Processing those dusts through thermo-plasma, we can withdraw Zn and Pb at the high pressure of steam from the top of the furnace, other metals such as Fe, Cr, Ni at melted state from the bottom of the furnace.
一
>>153
Furthermore, processes to withdraw platinum-groups from abandoned catalysts for motor-vehicle, processes to re-withdraw aluminum from alumidolos resulted from melting and casting aluminum by melting through arc-plasma have been developed.
As the above, thermo-plasma has already been practically used in various fields for waste-disposal.
一
>>154
Besides, thermo-plasma was widely used as a heat source at high temperature in the field of material-processing, for example, plasma-spraying.
But, only characters at high temperature of thermo-plasma are used in most of these applied examples.
Furthermore, thermo-plasma has a fascinating property called 〝high chemical activation″ too.
Properly using charged particles and radicals in the thermal plasma together with its high chemical activation, new processes for waste-disposal also will be developed.
These processes are shown in the following.
一
2.1 The decomposition of CFC ( Chloro-Fluoro-Carbon )
To resolve environmental problems originating in CFCs , it's required to suppress the release of CFCs into the atmosphere by properly decomposing CFCs.
The plasma-method, the combustion-method, the cement kiln-method, the oxygen-hydrogen flame-method, etc were acknowledged as valid technologies to decompose CFCs in countries signing the Montreal protocol.
In the case of the method for decomposing CFCs by plasma, methods using arc-discharge, microwave-discharge and corona-discharge have been practically used.
Here, the method for decomposing CFCs by RF-plasma with steam is shown.
一
>>156
A plant to decompose CFCs by high-frequency ( RF ) thermal plasma with steam is put in I city of Japan.
This plant can decompose CFCs at 70 kg/h by generating the 100 %-steam plasma from the 200 kW-power under the 200 torr-pressure.
The total reaction to decompose CFC-11 ( CCl3F ) through steam-plasma is as follows.
CCl3F ＋ 2 ( H2O ) → CO2 ＋ 3 ( HCl ) ＋ HF
( 1 )
In the case without steam, disproportionations to generate CCl2F2 and CClF3 and demerization reactions to generate C2Cl3F and C2Cl3F3 appear, and the generation of soot also is confirmed.
To suppress these side-effects is one of the advantages on the use of steam-plasma.
When CFCs are decomposed through steam-plasma, HF and HCl also are generated.
一
>>157
Letting these decomposed gases through water, HF and HCl can be removed as solutions.
And, the water temperature can be lowered into below 80 ℃ by directly passing decomposed gas through water, so that the re-composition of dioxin can be suppressed.
After that process, issued gases are purified in a scraba or a building to remove active carbons.
In the case of PLASCON-plasma process in Australia, CFCs are decomposed by supplying steam into a DC plasma jet. http://www.plascon.com.au/
一
>>158
The system can decompose CFC-12 ( CF2Cl2 ) at 40 L/min through the 150 kW plasma jet, if the ratio of supply-quantity to the power of plasma is set up below 6 mol/kWh, CF3Cl generated from side-effects can be suppressed.
In particular, the use of steam as plasma-gas can more effectively suppress the generation of CF3Cl and CF4 compared with the use of oxygen.
And, in Germany, a pilot plant to decompose CFCs through DC-plasma jet of 100 % steam has been developed.
「Hazardous Waste Destruction」 http://www.youtube.com/watch?v=atFPpBWl31o
一
>>159
2. The waste disposal by steam plasma
2.2 The decomposition of halon
Halon is a kind of CFC including bromine, the matter has been used for computer-rooms, electric rooms and fire-extinguishing equipments in forbidden places of the use of water such as parking areas.
But, as halon was specified as a matter to cause environmental destruction, the production of this matter has been stopped.
However, methods to properly process abandoned halons also have never been established ( in 2011 ).
The decomposition of halon is costly, technologically more difficult than that of CFC .
一
>>160
In such a situation, the method to process halon by thermal plasma has been regarded as one of the efficient methods to decompose halon.
※ As about 98 % of managed halons correspond to halon 1301 ( CBrF3 ), the establishment of method to process halon 1301 is an emergency subject.
The decomposition of halon is being carried out through steam RF plasma shown in a previous section.
It has been achieved to decompose halon 1301 at 50 kg/h under the same condition as that of CFC .
The total reaction of halon 1301 with steam-plasma is as follows.
CBrF3 ＋ 2 ( H2O ) → CO2 ＋ 3 ( HF ) ＋ HBr
( 2 )
一
>>161
The research to decompose halon with techniques of PLASCON stated in the above also is being continued.
In the case of decomposition of CF2ClBr with steam, if the ratio of supplied quantity to plasma-power is below 10 mol/kWh , un-decomposed halons can be ignored.
And, HBr, HF and HCl can be removed as solutions by making decomposed gases alkaline.
However, a defect in ways to make decomposed gas alkaline is that the facility for drainage tends to be large-scale.
一
>>162
Recently ( about 2011 ), the dry-thermal decomposing-method is being considered to withdraw bromides and fluorines generated as decomposed CFC-gases by reacting them with solid-alkaline materials such as calcium oxide and magnesium oxide.
The system for waste-disposal without water-processing like this is economically advantageous.
The total reaction of halon 1301 with burnt lime is as follows.
CBrF3 ＋ 2 ( CaO ) → CO2 ＋ 3/2 ( CaF2 ) ＋ 1/2 ( CaBr )
( 3 )
一
>>163
One of the features of dry-thermal decomposing-method is to solidify fluorines & bromines resulted from the decomposition of halon into CaF2 & CaBr2 and efficiently withdraw those solidified matters.
2.3 The decomposition of tire
The process to re-use combustion heat resulted from the burning of abandoned tires has been regarded as one of the ways to process abandoned tires.
But, in this case, the generation of harmful issued gases such as NOx, CHx and SOx, etc is inevitable, and heavy-metals such as Hg, Zn, Cd also are contained in those issued gases.
So, way to synthesize fuel-gas through thermal decomposition is more suitable than burning for processing abandoned tires.
一
>>164
In particular, when the thermal decomposition of abandoned tires is carried out through thermal plasma, the fuel-gas of C2H2, CH4, C2H4, H2, CO, etc can be efficiently synthesized.
The mixed gas of argon or argon-hydrogen is used as a plasma-gas and the steam is supplied into the lower stream of plasma-jet at 3 kg/h in this process.
Processing tires turned to be like dusts in about 500 μm through 80 kW of plasma-jet at 1.5 〜 4 kg/h , fuel-gases equal to 4 〜 7 MJ/m＾3 can be synthesized.
一
>>165
It's important to control the generated quantity of ZnO , SOx , NOx in processing abandoned tires.
The process with thermal plasma can suppress the issued quantity of SOx and NOx so as to be below 100 〜 200 ppm , can gather ZnO through a filter.
So, the process to decompose abandoned tires through thermal plasma also is remarkable.
一
>>166
3. The waste disposal by plasma at reduction mode
3.1 A way to turn molten flying dusts to be harmless
About fifty million tons of urban garbages a year are issued in this country, 70 % of them are burnt.
Several % of high volatile heavy-metals such as Pb and Zn are contained in burnt flying dusts which are generated in garbage dumps.
一
