4:Ground Stone Redux:2019/11/12(火) 05:29:39 ID:.CwsIRrI0
>>3
The replacement with an artificial joint has following three main tasks.
① bearability
② movability
③ painless
Namely, movability with bearing one’s weight and movability with no pains are requested.
These are necessary points to enable a human being to independently make the daily life.
Concrete characters requested to future type artificial joints are summarized into following two points.
( 1 ) articular functions sustained for a long term
( 2 ) improvements in articular function
5:Ground Stone Redux:2019/11/12(火) 05:41:10 ID:.CwsIRrI0
>>4
The former task is to reduce stresses originated in replacement and prolong a lifespan at healthy condition namely to develop an artificial joint usable without being exchanged for a long period.
Meanwhile, the latter task is to recover individual life activities such as work, sport and hobby.
Improvements in economic & social activity for patients are necessary to assure of the usefulness of the artificial joint as a new technology.
一
6:Ground Stone Redux:2019/11/12(火) 05:55:40 ID:.CwsIRrI0
>>5
In this section, we mention main points of maintenance of joints for a long period and its improvements in performance, limits of artificially ‘produced’ joints and new aspects of ‘grown’ joints with regenerative technologies.
Furthermore, we briefly introduce ways to prepare communication-environments ( communications about risks, risky communications ) required to find out new ways for healing damaged joints into this section too.
7:Ground Stone Redux:2019/11/13(水) 05:19:10 ID:r5.ITLX.0
>>6
5.2.5-1 Maintenance of articular function for a long period ( structural healthiness in wide meaning )
The replacement of artificial joint is clinically generalized as an articular constructive method taking movability into consideration.
But, the ‘structural healthiness’ of the artificial joint as an industrial product has never been established yet ( about 2013 ).
‘Structural healthiness’ as a term means a generic durability including fatigue resistance, abrasion resistance.
8:Ground Stone Redux:2019/11/13(水) 05:31:17 ID:r5.ITLX.0
>>7
It’s hard to find out a machine which continues to work without maintenances for a long period of about 20 years except for artificial joints in various industrial products.
Furthermore, in case of artificial joints, it’s needed to estimate ‘structural healthiness’ in wide meaning with bearing biological interactions on the interface between a living tissue and a material in mind.
9:Ground Stone Redux:2019/11/13(水) 05:49:42 ID:r5.ITLX.0
>>8
Ultra High Molecular Weight Polyethylenes ( UHMWPE ) which were applied to clinical fields by Charnley are being generally utilized as rubbing materials for artificial joints for now.
It’s rare that rubbing functions are lost due to abrasions.
But, as polyethylene abrasion granules at submicron in size cause osteo-lyses, further, loosenings between the artificial joint and osseous tissues,
it’s important to reduce the quantity of abrasion and suppress osteo-lyses for prolonging the lifespan of artificial joint.
10:Ground Stone Redux:2019/11/13(水) 06:22:35 ID:r5.ITLX.0
>>9
An idea of cross-linked polyethylene proposed by Oonishi and others was mainly applied to artificial hip joints, it considerably contributed to improvement in abrasion resistance.
Furthermore, a way to graft 2-methacryloyloxyethyl phosphoryl-choline ( MPC ) onto the polyethylene-surface of the rubbing part of an artificial hip joint at nano-scale ( MPC-processing ) was devised by a collaboration of the orthopaedic class of the medical department and the faculty of engineering of Tokyo-university, this way also remarkably improved abrasion resistance.
And, Tomita and others in Kyoto-university showed that mixing dl-α-tocopheral as a kind of vitamin E with polyethylene before molding can prevent oxidative fatigue fractures of polyethylene for artificial joints.
11:Ground Stone Redux:2019/11/13(水) 20:51:37 ID:CEDLc7Ho0
>>10
By the way, the most important factor to determine the lifespan of an artificial joint is bone-absorption.
This bone-absorption is caused by reactions of polyethylene abrasion granules in a living tissue.
Both technologies shown in the above can suppress reactions of abrasion granules with living tissues.
As the above, new material technologies have possibility to prolong the lifespan of an artificial joint including an artificial hip joint and an artificial knee joint.
а
12:Ground Stone Redux:2019/11/13(水) 21:01:32 ID:CEDLc7Ho0
>>11
But, in experiments of the former MPC-technology, activations of actually generated abrasion granules in a living body have never been made clear yet.
And, even in experiments of the latter polyethylene containing vitamin E , activations of abrasion-granules under the same complete aseptic condition as an inner-living body have never been made clear yet ( in 2013 ).
к
13:Ground Stone Redux:2019/11/13(水) 21:12:45 ID:CEDLc7Ho0
>>12
A device to realize an aseptic frictional state in vivo is shown in Fig 24 .
It’s possible to freely prepare an optional rubbing state matching with the artificial hip joint and that matching with the artificial knee joint with this device.
Systems to measure its bio-activations at the contact of abrasion granules generated by such a device with living cells are being developed.
14:Ground Stone Redux:2019/11/13(水) 21:30:18 ID:CEDLc7Ho0
>>13
The primary problem to develop artificial joints until now is that there have never been ways to directly the extent of osteo-lysis as the main factor to determine its lifespan and its performance.
Therefore, general industrial ways for examination have been applied to estimating materials for artificial joints without taking the differences between a living body and a matter into consideration.
But, as a device to generate abrasion granules at aseptic state and various rubbing conditions was developed, it has enabled to investigate bio-activations of abrasion granules at higher accuracy.
一
15:Ground Stone Redux:2019/11/14(木) 05:00:48 ID:aBjyCzo60
>>14
5.2.5-2 Further improvement in articular function ( artificial joints matching for life-demands and re-generative joints )
As stated previously, it’s important to reconstruct articular functions matching for individual life demands such as works, sports and hobbies for developing future type artificial joints.
For instance, it’s often reported that a famous pro-golfer continues playing a golf after receiving a replacement operation with an artificial joint.
16:Ground Stone Redux:2019/11/14(木) 05:08:54 ID:aBjyCzo60
>>15
Furthermore, recently, it’s requested to design artificial medical materials matching individual conditions and hobbies.
Especially, it’s getting possible to produce artificial joints so as to match them with individual shapes of bone and life-styles owing to the appearance of customized artificial joint.
17:Ground Stone Redux:2019/11/14(木) 05:19:52 ID:aBjyCzo60
>>16
However, if we continuously make a more active motion with a mechanical matter such as artificial joints, its durability of the mechanical tool also will be lowered.
And, even though we provisionally succeed in the prevention of osteolysis, as its functions are sustained under the constant exchange of components, it’s unlikely that an artificial matter semi-permanently plays stable functions.
18:Ground Stone Redux:2019/11/14(木) 05:39:13 ID:aBjyCzo60
>>17
For example, athletes basically have same joints as those of general people in structure.
But, joints of athletes are endurable to tens times more extreme motions than usual motions.
Those mechanisms have never been made clear yet ( about 2013 ).
However, joints of living being seem to have functions to keep the low frictional state with adjusting themselves against extreme conditions.
Technologies to re-generate such living tissues, further, systems to heal damaged joints including re-generative processes are being realized.
一
19:Ground Stone Redux:2019/11/14(木) 05:49:09 ID:aBjyCzo60
>>18
But, as regenerative treatments for cartilage at present are applied to only cases with widely damaged articular cartilages of deforming osteo-arthritis and chronic rheumatoid arthritis,
we must develop treatment-systems taking bearability, movability and painless into consideration from now.
一
20:Ground Stone Redux:2019/11/14(木) 06:08:53 ID:aBjyCzo60
>>19
For instance, as the appearance of deforming osteoarthritis includes the bad circle of deformation → failure in dynamical balance → failure in lubricant function → damaged tissue → deformation as a main factor, even if the cartilage is regenerated, the same symptom appears again.
Accordingly, we must combine the correction of this deformation with the regeneration of cartilage and the reconstruction of mechanism to support a weight.
21:Ground Stone Redux:2019/11/14(木) 06:24:06 ID:aBjyCzo60
>>20
As the effectiveness of ways to mold a bone so as to be a proper shape to each condition for correcting considerable deformation ( arthroplasties including corrections of dynamical environments such as formation of acetabular and bone cutting operation for higher tibia ) has been already, widely known,
future-type treatment systems for joint in which above arthroplasties are combined with technologies to regenerate cartilage are being prepared ( about 2013 ).
к
22:Ground Stone Redux:2019/11/14(木) 21:26:16 ID:aBjyCzo60
>>21
Fig 25 shows a treatment system to which a technology to regenerate cartilage is added after an arthroplasty such as bone cutting operation for higher tibia and formation of acetabular.
Under the treatment system, a fibroin-sponge with one highly strengthened membranous side is pasted on the injured part to which an arthroplasty and an operation to promote the re-generation of cartilage ※ are applied.
※ A hole is made on the surface of the joint, the treatment to easily lead inner-cells to an injured part through such a hole.
23:Ground Stone Redux:2019/11/14(木) 21:41:50 ID:aBjyCzo60
>>22
Fibroin is a protein extracted from a refined silk thread.
If cells are scattered over a fibroin-sponge ( a kind of porous medium ), healthy chondral tissues are formed around the put cell.
And, the following case is reported in a clinical model applied to kneecap ( replacement surgery for a patellofemoral joint ).
In the case, if a silk-fibroin over which chondral cells are scattered is pasted on a lost chondral part, chondral tissues similar to articular cartilages are actually formed after 2 〜 6 weeks.
24:Ground Stone Redux:2019/11/14(木) 21:54:19 ID:aBjyCzo60
>>23
Chondral tissues formed near the pasted fibroin are bonded to the joint, both scattered cells and cells near the joint are shifted to the injured part, consequently, chondral tissues are formed on the injured part.
с
25:Ground Stone Redux:2019/11/14(木) 21:59:22 ID:aBjyCzo60
>>24
Furthermore, it was found out that even if scattered cells are replaced with own bone marrow cells, chondral tissues are well repaired.
е
26:Ground Stone Redux:2019/11/14(木) 22:14:06 ID:aBjyCzo60
>>25
Accordingly, when bone marrow liquids extracted in performing a surgery are injected into a fibroin-sponge without culturing in vitro,
if the fibroin-sponge ( into which bone marrow liquids are injected ) is pasted on the damaged part, it’s expected as a new treatment method to self-organize cartilages under the pasted part.
But, why proteins refined out of silks have such healing effects has never been made clear yet ( in 2013 ).
27:Ground Stone Redux:2019/11/14(木) 22:23:16 ID:aBjyCzo60
>>26
According recent researches, it has been made sure that a cluster composed of cells moves around in a fibroin-sponge.
It’s supposed that cellular clusters formed in this fibroin and cells in vivo cooperatively generate functional tissues near the material.
28:Ground Stone Redux:2019/11/15(金) 04:15:31 ID:H0YUDWRA0
>>27
5.2.5-3 Development of medical technology on life and risk communication
In technological development for medicine & welfare, it’s often insufficient for improvement in medical level to prolong lifespan and remove pain.
For example, even if it becomes possible to save a life from some intractable disease owing to medical progress, it’s possible that the person survives with certain disability.
Actually, such cases are increasing.
29:Ground Stone Redux:2019/11/15(金) 04:31:42 ID:H0YUDWRA0
>>28
Furthermore, regarding this country as a family of 20 members hypothetically, it’s supposed that 10 members of them work, those 10 members bear remaining 10 members.
In this case, if the work of one person of working 10 members is to take care of a sick person, then substantially 9 members bear lives of 20 members.
Medical・welfare works are included in a main mature industry in the future.
By the way, if two members of 10 members take care of two sick persons as its main tasks, is it actually possible that 8 members bear lives of 20 members ?
30:Ground Stone Redux:2019/11/15(金) 04:44:01 ID:H0YUDWRA0
>>29
The increase of borne medical expenses until now has been supposed by improvement in productivity in society.
But, keeping exhaustion of resources, reconstruction of old buildings in mind, we can’t expect improvement in productivity over the whole society so much.
31:Ground Stone Redux:2019/11/15(金) 04:52:16 ID:H0YUDWRA0
>>30
And, the ratio of supported people also rapidly increases due to the appearance of aging society.
Accordingly, to develop technologies related to medicine & welfare in the future, we must sufficiently consider about respective factors including sustainability, necessity of the technology.
а
32:Ground Stone Redux:2019/11/15(金) 05:27:27 ID:H0YUDWRA0
>>31
Recently, technologies to cure articular diseases have been paid attention.
Because this technology can contribute to improvement in independence and social economic activity.
Then,
① Maintenance of articular function for a long period
② High-functionalization of joint
These two aims are essentially important to improve not only independence of a patient but also individual economic & social activities such as work, sport and hobby and to give sustainable useful mechanisms to this technology in society.
33:Ground Stone Redux:2019/11/15(金) 05:39:03 ID:H0YUDWRA0
>>32
However, there are still many rooms to consider what technology truly improves qualities of individual lives, and it’s important to prudently expand the applied range without blindly obeying the market mechanism.
Future-type medical treatments for damaged joints should not be separated from the viewpoints of life in other words individual standards of value and ideals of health.
34:Ground Stone Redux:2019/11/15(金) 05:53:24 ID:H0YUDWRA0
>>33
It’s called ‘risk communication’ to share sense of values among concerned people with mutually considering effectiveness and risks of treatment-technologies from the viewpoint of daily lives.
Recently ( about 2013 ), this risk communication has been attracted.
This concept called ‘risk communication’ has been known as a method to briefly explain risks related to technologies such as nuclear power generation for local residents.
35:Ground Stone Redux:2019/11/15(金) 22:21:03 ID:eor6U2Rk0
>>34
But, originally, this term means to fundamentally reconsider about various factors requested of technology and technique or to construct such a field among different people in sense of values.
For example, Tomita chose dl-α-tocopherol ( a kind of vitamin E ) to develop vitamin E-added polyethylene for prolonging the lifespan of an artificial knee joint.
The main reason was based on the following somewhat subjective judgment by this developer.
36:Ground Stone Redux:2019/11/15(金) 22:29:09 ID:eor6U2Rk0
>>35
Namely, as this matter is originally contained in a living body, unknown risks may scarcely happen in comparison with a complete foreign substance.
Probably, patients will comparatively easily receive such an ‘expectation of safety’ ( which is different from scientific criteria ).
37:Ground Stone Redux:2019/11/15(金) 22:42:55 ID:eor6U2Rk0
>>36
And, fibroin-sponge ( protein refined from silk ) has been selected to develop a paste-type system for re-generating cartilage.
The primary reason was that this material had being utilized for surgical operation over a long history rather than cell delivery function ( tissues are originated near the material ).
Above criteria are not informations to quantitatively and objectively confirm its safety.
с
38:Ground Stone Redux:2019/11/15(金) 22:50:51 ID:eor6U2Rk0
>>37
Rather, provisionally, these choices are based on subjective ( or empirical, intuitive ) ‘senses of security’ from unknown risks.
But, when it’s hard to objectively and quantitatively estimate safety, such ‘senses of security’ play significant roles under risk communication.
39:Ground Stone Redux:2019/11/15(金) 22:59:13 ID:eor6U2Rk0
>>38
In medical fields such as orthopedics which don’t directly determine whether life or death but have relations to improvement in quality of daily life,
these ‘senses of security ( or safety )’ are especially significant to deal with unknown risks at very low probability which are difficult to scientifically forecast.
40:Ground Stone Redux:2019/11/15(金) 23:05:50 ID:eor6U2Rk0
>>39
And, when new technologies for medical treatment and welfare are developed, it’s the essence of risk communication and sense of safety to ask following questions to doctors and developers themselves.
41:Ground Stone Redux:2019/11/15(金) 23:13:49 ID:eor6U2Rk0
>>40
For example,
‘Do you want to apply technologies that you are developing at presnt to yourself and your family?’,
‘If you are a doctor, will you perform the medical treatment being executed on the patient on yourself and your family?’, etc.
42:Ground Stone Redux:2019/11/15(金) 23:21:12 ID:eor6U2Rk0
>>41
It’s necessary for developing technologies for medical treatment and welfare that the developer shares senses of values with users with questioning ‘is it truly safe?’, ‘is the technology truly required?’, etc.
From 「Artificial Medical Materials」,
5.2.4 High Molecular Materials for Promoting Calcification
5.2.4-1 Bone-regeneration by organic-inorganic hybrid materials
A living bone has composite structures of proteins such as collagen with hydroxyapatite ( HAp ) at molecular level,
metabolisms are constantly repeated between osteoclasts and osteoblasts under osteocytes sensible to stresses.
Osteo-structures are kept due to repeated metabolic exchanges.
>>44
In general, an autogeneous bone taken out of a healthy part is grafted onto an injured part to heal a lacked bone originated in fracture and to cure of a tumor generated on a living bone.
But, in such cases, we must take risks such as damages of the healthy part and complications into consideration.
一
>>45
Meanwhile, in cases of treatments to graft an artificial material for filling in a lacked part of bone, if such a material is precisely designed at molecular level, it’s expected not only to avoid risks but also to promote bone-regeneration.
By the way, main characters demanded of osteo-filling are as follows.
>>46
・ New generation of bones is induced by formations of bones.
・ The material is quickly absorbed into living tissues.
・ The material does not cause rejections including allergic reactions.
The hybridization of organic ingredients with inorganic ones is a main key to give above material merits to an implanted object.
>>47
Hybrid materials are categorized into the 4th possibility following high molecular-, metallic-, ceramic- 〜 .
And, it’s supposed that complementariness between respective components remarkably improves those properties.
>>48
On the other hand, HAp is the main ingredient contained in the enamel of a tooth and a living bone.
And, this ingredient is composed of calcium ions, phosphate ions and hydroxide ions.
※ Chemical quantitatively, it’s expressed as Ca 10 ( PO 4 ) 6 ( OH ) 2 .
Holes are made on the ingredient under some condition, phosphate ions contained in it are replaced by carbonic ions.
As the above, this ingredient shows various compositions dependently on adjustment, condition.
>>49
Hybrid materials simulating above structures at molecular level have been actively studied.
Actually, materials containing HAp and calcium phosphate have been already practically used.
But, HAp until now is poor in bio-resolvabity because of its high crystalline features, therefore, it has been hard to replace it with a living bone ( in 2013 ).
с
>>50
5.2.4-2 Developments of nanostricture-controlled hybrid materials
Under the above background, Taguchi and Akashi paid attention to the alternate immersion method as a way to precisely control the structure of an interface.
And, they developed HAp-gel ( Hydroxyapatite agarose gel ) as a nano-hybrid material by compounding HAp or CaCO3 ( calcium carbonate ) as an inorganic ingredient with agarose gel as an organic ingredient.
一
>>51
In this way, two kinds of solutions respectively containing inorganic ions composing HAp or CaCO3 are prepared.
And, agarose gel is alternately immersed in these two solutions.
So that, formations of crystals are induced on the surface of the ground material.
In this case, it’s possible to control the quantity of HAp generated on the ground material on the immersed time, the number of steps.
>>52
Further significantly, as HAp prepared in this way has low crystalline characters, its resolvability in vivo is high.
Accordingly, the quick absorption of a material into living tissues and quick bone-formations after implantation are expected.
с
>>53
The speed required to produce the HAp-gel by this method ( alternate immersion method ) is 100 times faster than that by the method until now ( bio-simulated reaction ).
As the number of alternate immersions increases, HAp goes to be developed around the agarose gel.
5 cycles of alternate immersion can form HAp for 1 〜 6.5 mg of agarose gel at dry state.
HAp-crystals composed of granules of 200 〜 300 nm in span were formed in the inside.
>>54
And, we found out diffraction patterns proper to HAp through X-ray crystallographic analysis.
Accordingly, we found out the possibility to compose a new hybrid material made of HAp by alternate immersion method.
а
>>55
5.2.4-3 Estimations of bone-regeneration and the quantity of generated bones on implantation-tests in animals
Because HAp produced by this method ( alternate immersion method ) are low in crystality, it’s supposed that though this ingredient induces bone-generation, on the other hand, it can be resolved and absorbed into the living tissue.
Then, an implantation test in a macaca fascicularis was executed to make sure of usefulness, safety for bone-generation under cooperation between medicine and engineering.
>>56
HAp-gels had been homogenized so as to be like a paste for improving operability, such gels had been implanted into a macaca fascicularis with extracted teeth and the state after 90 days from the implantation was observed.
So that, it was made clear that bleeding is stopped within one-minute at the implanted part in comparison with parts without such treatments and the treatment promotes regeneration of alveolar bone.
一
>>57
It’s indispensable in dental treatment to stop the bleeding after pulling out a tooth.
Accordingly, it’s significant that this HAp has not only high absorbability but also good effects originated in components to stop the bleeding.
And, it’s known that it’s possible to regenerate osseous tissues with bone-fillings on-around which formations of HAp are further promoted by electro-chemical methods.
>>58
By the way, taking materials suitable to hard tissues into consideration, resolvability and absorbability are demanded even in some cases which have lower dynamical strength than a living bone.
Here, HAp-gels were implanted into a lacked thigh bone of a rabbit, and we qualitatively estimated bone-regenerative processes in this case.
※ Then, the lack of 5 mm in diameter, of 10 mm in depth.
>>59
Respective states over regenerative processes after the implantation were successively checked with micro-CT .
After two weeks from the implantation, bone-regeneration started around the implanted part.
Furthermore, after 4 weeks from the implantation, regeneration of osseous tissues is actively developed around the implanted part.
с
>>60
These results shows that regeneration around the part into which HAp-gels were implanted was significantly more active than those around the part into which agarose gels were implanted.
※ In a word, a part into which HAp-gels were implanted was more active than a part into which agarose gels were implanted in regeneration.
>>61
And, as most of materials for bone-filling until now were radio-opaque, it has been difficult to catch those opaque parts through X-rays.
But, as this HAp-gel has radio-lucency, it’s possible to easily and successively catch transitions of newly developing bones around the part filled with this material by X-rays.
>>62
Furthermore, HAp was implanted into a lacked part of a bone of a rat, we quantitatively estimated variations of the quantity of bone after the implantation.
Then, the quantity of regenerated bone was calculated out as follows with a bone density measuring device.
・ Plural virtual squares and cuboids covering each lack were assumed.
・ And, the quantity of bone was derived from weights of bones contained in those respective ‘sections’ or ‘units’ .
>>63
So that, the bone-density at a part filled with HAp-gel remarkably increased in comparison with parts filled with other materials.
Accordingly, HAp-gel is effective in not only filling of lacked part but also bone-regeneration.
а
>>64
5.2.4-4 Applications of HAp-gel to clinical fields
It was made clear through animal tests that HAp-gel was useful as a filling to induce bone-regeneration.
Clinical studies are being executed under the cooperation between medicine and engineering to practically use this material in the dental field.
一
>>65
At present ( about 2013 ), to make sure of the safety of HAp-gel based on ISO 10993 , clinical researches for that are being executed by Prof. Masashi.Tabata ( the dental surgery of Miyakonojyou-hospital of Miyazaki prefecture ) and an Assistant Prof. Souichi. Iwai ( the dental department of Osaka university ).
с
>>66
We show some of those outlines here.
Following clinical observations were executed under the cooperation between the dental department of Osaka-univ and engineering.
A patient had a lack on one’s own bone after the extraction of cysts on the lower jaw.
Then, HAp-gels were implanted into the lacked part, we checked bone-generation before and after the surgery through X-ray photography.
>>67
For now, clinically harmful problems ( infection, prolonged inflammation, prolongation of time required to heal wounds, etc ) have never been found out.
As shown in pictures, we find out that bone-regeneration remarkably develops after about 12 months from the implantation.
а
>>68
Next, we attempted to implant this material into a cleft jaw of a patient suffering from cleft lip and palate in another clinical case.
When a transplant operation is performed on the cleft part of a cleft lip and palate patient,
as it’s possible to sufficiently perform an operation within the mouth, osseous tissues are generally taken out of maxilla or mandible bone due to lower invasiveness to minimize the stress on the patient.
In the case, the main problem is whether the possible quantity to take is small or not.
>>69
Then, we mixed this filling ( HAp-gel ) with PCBM ( Particulate Cancellous Bones & Marrows ) taken out of a chin bone to increase the grafted quantity.
And, the implanted part was observed after six months from the transplantation, we found out that osseous tissues were actively generated around the cleft part.
к
>>70
Following possibilities have been made clear owing to this result.
・ Bone-transplantation on only a small quantity of chin bone
・ Remarkable reduction of invasiveness on a patient with small quantities of bones such as children, in hospitalization period
>>71
Furthermore, in an other case, HAp-gel was applied to a patient suffering from a serious periodontosis ( this case was presented by the dental surgery of Miyakonojyou hospital in Miyazaki prefecture ).
一
>>72
Front teeth on the left lower jaw had been lost to sharpened root parts due to serious periodontosis.
But, we found out that osseous tissues were regenerated around roots of teeth by filling those lost parts with HAp-gels.
с
>>73
It was made sure through animal experiments that the hybrid material of agarose gel with HAp as a bio-high molecular material can induce bone-regeneration.
Furthermore, it also was clinically made clear that this material can be effective in healing various diseases such as lacked ( broken ) bone, cleft jaw, periodontosis.
а
We also heard that the fellows habitually presenting undesirable advertisements including vulgar ones and fraudulent ones on the net would fight against the world as their enemies from now.
с
Indeed, we also heard that the chaps habitually presenting e×tremely erotic advertisements and vulgar ones on the net would fight against the world as their enemies from now.
91:Ground Stone Redux:2020/08/22(土) 17:03:19 ID:1mHKElfQ0
Indeed, we also heard that the people habitually presenting undesirable advertisements such as e×tremely erotic contents and unreliable ones dealing with defective products and fakes on the net would be conveyed to purgatories due to the judgment by the king of Enma (閻魔).
We also heard that the people habitually presenting undesirable contents such as e×tremely erotic & vulgar contents on the net would fight against the world as their enemies, and they would be transferred to ‘purgatories’ .
115:介良事件、甲府事件は wiki にあるのに 仁頃事件がない怪:2021/03/08(月) 14:47:24 ID:NPfbnEgQ0
We heard that the people habitually making violent & annoying noises for intentionally bringing uneasy feelings & harassments to us would fight against the world from now.
а
Xmas ;
It’s supposed that respective bands and a gap between bands are embedded in a 2D plane, the embedded gap-zone is ‘twisted’ .
Besides, edges of the ‘twisted gap’ could be viewed for intersecting (≒ crossing) edges.