합성 생체재료가 응급 외상 상황에서 핵심이 될 수 있다

인공 혈소판으로 출혈 ‘치료’

A lot of deaths from injuries and accidents are linked to blood loss. While not as discussed as cancer, cardiovascular, or genetic diseases, this is a segment of medicine that can greatly 보다 첨단 기술의 혜택을 크게 받을 수 있어 생명을 구할 수 있는 분야입니다.

In current ER treatment, transfusion of platelets, the cells responsible for coagulation, is often required to manage bleeding.

The way platelets work is by responding to a signal sent by the body of an injury, making the platelets travel to the injury site. Once arrived, the platelets will clump together to form a clot helping to stop the bleeding.

출처: Byjus

The clot itself is formed by the agglomeration of platelets and fibrin, a fibrous protein present in the bloodstream. The whole process is also mediated by 13가지 이상의 다양한 응고 인자.

출처: 혈소판.

However, the problem is that the storage of platelet transfusions is difficult, reducing its utility in a pre-hospital setting. Among the issues are “제공자 부족, 보관 및 이동의 어려움, 높은 세균 오염 위험, 그리고 매우 짧은 유통기한(~5~7일)”.

Platelets remain the “final frontier” of blood component transfusion in the pre-hospital setting, and data supporting improved outcomes with early platelet transfusion in massive hemorrhage strongly support the rationale to move platelet transfusion forward along with PRBCs and plasma.

생체 모방 인공 혈소판: 과거, 현재 및 미래.

Bleeding from a traumatic injury will never stop being dangerous, no matter what other advancements we make in genetics, cell biology, or artificial organs. As bleeding is a major cause of death before reaching the hospital, another solution than platelet transfusion is needed.

While many efforts have been spent on improving the storage and utility of natural platelets, artificial platelets are another alternative.

Leveraging progress in nanotechnology, this concept might become a reality sooner than expected, thanks to researchers at the North Carolina State University, University of Virginia, Duke University, and Chapman University, and their results published under the title “초연성 혈소판 유사 입자가 설치류 및 돼지 외상 모델에서 출혈을 멈춘다”.

인공 혈소판

Several efforts have been made in the past to develop artificial platelet systems.

Using natural platelets together with artificial systems has been proven to solve most of the problems associated with natural platelets. More promising is the use of artificial nanoparticles linked to proteins or fragments of proteins.

This is what the researchers discussed above have done, creating synthetic platelet-like particles (PLPs). They were designed using ultrasoft and highly deformable nanogels coupled to fibrin-specific antibody fragments.

The fibrin-binding ligand was designed to target wound sites and enhance blood clot formation.

The flexible nanogel particles were also able to change shape in a similar way to real platelets. This improved clot stability and contributed to the healing.

훌륭한 결과, 좋은 안전성

In vitro, the PLP selectively bounded to fibrine and improved clot formation.

In animal models (rodents and pigs), the PLPs reduced blood loss without off-target clot formation, a very important point, as unwanted blood clots could be as deadly as blood loss. It could even cause strokes or heart attacks.

The blood losses were strongly reduced, even when the blood was partially replaced by fluids without adequate coagulation factors (“dilutional coagulopathy”).

The effect on blood loss worked both as a preventive measure and for immediate treatment after an injury.

Equally importantly when it comes to the safety profile, the PLPs were removed by the kidneys efficiently, proving that the body can eliminate them safely once the injury and blood loss has passed. This might have been helped by the flexible shapes of the gel’s nanoparticles.

인공 혈소판의 인간 적용 가능성

응급실 및 외상

Coagulation is a biological mechanism highly conserved throughout all mammals, so there is a very high chance that the PLPs we discussed will work in humans as well.

The obvious main application of this technology is in emergency treatment, especially in ambulances and first responders’ medical kits.

외상은 45세 이하 어린이와 성인의 주요 사망 원인이며, 연간 약 31,000명의 미국인이 예방 가능한 출혈로 사망하고 있습니다, this is a massive health crisis that nanotechnology could mostly solve. Especially if combined with making paramedics carry blood systematically.

출처: Dallas News

위험한 활동 및 군사

By improving the treatment of injury, the US military reduced mortality rates for troops serving in Afghanistan by nearly 50% from 2005 to 2013.

They did it with the help of a tourniquet (which limits bleeding on limbs) and giving blood on the way to the hospital.

Easy enough to store and carry, artificial platelets will likely be part of most military base medkits as soon as the technology is proven safe for humans.

This would be an application where PLPs would be even more vital than civilian use, as injuries are likely to happen away from a hospital, and the blood supply might be limited in case of intense combat action.

혈우병

Not all hemophilia types can be solved with PLPs, as some are due to incorrect fibrin proteins. Nevertheless, this disease, characterized by poor clotting, could be made much less dangerous in some cases.

It could even maybe make sense to use PLPs preventively, as long as repeated & long-term use of this technology has been proven safe.

혈액 및 혈소판 기업

Because artificial platelets are such a new technology, there is obviously no company commercializing them yet. However, we can assume that companies already in the field of blood transfusion and platelet production would have the distribution network and expertise to lead this healthcare revolution.

1. CSL Limited (CSL.AX)

CSL is a conglomerate selling biotech products like plasma products, gene therapies, and recombinants.

The plasma (derived from blood) segment is CSL Behring. With 100개 이상의 국가에 340개 이상의 혈장 채집 센터를 보유하고 있어, 회사는 혈장 시장의 3분의 1을 장악하고 있습니다.  The segment is also by far the largest revenue driver of the CSL group.

출처: CSL

The company is also a pharmaceutical/biotech company with an extensive R&D pipeline. It is mostly focused on vaccines, hematology/blood, respiratory, and cardiovascular. The group also recently added nephrology (kidneys) to its therapeutic segments.

출처: CSL

Thanks to its leadership in blood therapies and plasma collection, CSL is well-positioned to stay a leader of the segment and be among the first to provide artificial platelets as an additional item to the emergency healthcare toolkit.

2. Takeda

The Japanese Takeda is a diversified pharmaceutical company, with a presence in multiple sectors, including plasma.

출처: Takeda

Takeda has 230 facilities to collect plasma in the US and Europe, through BioLife Plasma services. It places it among the top 3 largest plasma organizations in the world, with 20 brands of products related to this sector and 80 years of activity.

Takeda is also very active in R&D, with 23 product candidates in phase 3 of clinical trials, with the 2 largest segments being gastrointestinal & inflammation, followed by plasma-derived therapies.

출처: Takeda

Like CSL, Takeda’s expertise in plasma should help it in bringing artificial platelets to the market.

It is also a company with an extensive strategy of partnerships with innovative startups, including in nanotechnology, for example, BioSurfaces’ nanomaterial, Cour Pharmaceutical Development’s nanoparticles,  or Leon-nanodrugs MicroJet Reactor.

So it could leverage such expertise in nano-design & fabrication to create its own version of PLPs, now that the proof-of-concept exists.