October 19, 2005
New Method Grows Collagen For Surgery Orders Of Magnitude Faster

University College London researcher Robert Brown and his team have stumbled upon a cell free way to rapidly produce collagen protein polymers for surgical repair of collagen damage.

A research team from the UCL Tissue Repair and Engineering Centre (TREC), the UCL Eastman Dental Institute and the UCL Institute of Orthopaedics, have pioneered a novel technique for engineering tissues, which has the capacity to greatly reduce the time taken to fabricate implantable human tissue.

Tissue engineering is a method whereby the patient has cells extracted from his or her body and grown under laboratory conditions for a myriad of applications such as cartilage, skin grafts, heart valves and tendons, without the risk of rejection, infection or the ethical dilemma involved in transplanting a donated organ.

Current tissue engineering methods depend on the ability of the cultured cells themselves to grow new tissue around a cell scaffold, which is slow, expensive and has limited success. Professor Brown’s process is cell-independent, controlled engineering of scaffolds by rapidly removing fluid from hyper-hydrated collagen gels.

The fluid is removed by employing plastic compression, a process that the team found produces dense, cellular, mechanically strong collagen structures that can be controlled at nano and micro scales and which mimic biochemical processes.

Principal investigator Professor Robert Brown (UCL TREC) said: “The fluid removal dramatically shrinks the collagen by well over 100 times its original volume, which provides the ability to introduce controlled mechanical properties, and tissue-like microlayering, without cell participation. Crucially, this takes minutes instead of the conventional days and weeks without substantial harm to the embedded cells. The rapidity and biomimetic potential of the plastic compression fabrication process opens a new route for the production of biomaterials and patient-customised tissues and represents a new concept in ‘engineered’ tissues.”

A paper describing the process in detail will be published in the October edition of the ‘Advanced Functional Materials’ journal.

The method takes 35 minues instead of weeks and is twice as strong as collagen made using existing methods.

Cell-seeded collagen gel typically takes weeks to develop into weak, early-stage tissues. In the UCL study, published today in Advanced Functional Materials online, the team sucked most of the water out of the structure in a procedure known as plastic compression rather than waiting for the cells to do their job.

The result - following huge-scale shrinkage by a factor of at least 100 - was a simple collagen-based tissue created in 35 minutes. The shrinkage – a new approach to microfabrication – also gave the tissue an average break strength of 0.6 MPa (megapascals) compared with tissues conventionally grown over 1 to 12 weeks of around 0.3 MPa. Given that collagen sheets are fragile – in the study they were around 30 micrometres thick – the team rolled them up like swiss rolls to produce 3D rods which were easier to handle and manipulate.

Tissue engineering typically involves placing cells on a polymer scaffold and allowing them to grow into the desired tissues, which can then be used for surgical implantation. The process can take days or weeks and is difficult to control, cells may also fail to develop into the target material and at best, produce a tissue of less than 1 MPa break strength compared with natural collagen which can be up to 100 MPa strong in a human tendon.

Collagen makes up a quarter of the body.

Collagen is a protein which acts as a structural support for skin, bone, tendon, ligament, cartilage, blood vessels and nerves and as such it makes up 25 per cent of the human body.

Collagen accumulates damage with age and injury just like the rest of the body. So the ability to produce collagen quickly for implant is another step down the road toward full body rejuvenation. However, since collagen's arrangement in so many locations in the body is so microscopic in structure and in so many different locations surgery is not a practical method of replacing all or even most worn collagen. A lot of the damaged collagen in an aged body will need to be replaced by cells sent into the body as cell therapy programmed to do collagen repair. Still, this latest discovery has uses for repair of larger sized pieces of collagen.

The discovery was made accidentally.

Professor Robert Brown, of the UCL Institute of Orthopaedics, says: “We stumbled across this discovery while trying to measure the compression properties of collagen gel. Our method offers a simple and controllable means of quickly engineering tissue structures. The next stage is to test whether this method could help repair injured tissues.

“The speed and control it offers means that our method could one day be used to produce implant tissue at the bedside or in the operating theatre. We have a proof of concept grant from UCL BioMedica to produce a semi-automatic device for implant production. Ultimately, the goal is to design a rapid, inexpensive, automatic process for creating strong tissues which could supply hospital surgical units with a tool kit of spare parts for reconstructive surgery.”

This result fits a larger pattern of bioscientific and biotechnological advances where smarter manipulation of biological molecules allows processes to be speeded up by orders of magnitude.

Share |      Randall Parker, 2005 October 19 11:00 AM  Biotech Tissue Engineering

epobirs said at October 20, 2005 5:26 PM:

This may not be immediately useful for rejuvanative therapies but should be huge for sports medicine. So there should be lots of money coming in for researching further applications.

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