Tag: healing

The Ultimate 2-for-1: the Power of Contralateral Strength Training

For the competitive athlete, injury often means loss. Loss of playing time, loss of skill development, and most importantly, loss of training time. These are all unfortunate consequence of getting a bone or tissue injury requiring a long-term healing prognosis. Injuries can be so devastating because the road to recovery is often times an arduous two-step process. First, the athlete must wait for their broken bones, torn ligaments, or pulled muscles to naturally heal. During this time, the athlete’s injured limb is likely immobilized in a cast or brace, leaving the resulting muscle to slowly atrophy as the body tries to heal itself. As a result, an athlete must spend the second part of their recovery process re-training the weakened muscles in the immobilized limb to return to full-strength. What if there was a way to heal and train the body at the same time? This is the power of a neurophysiological phenomenon known as “contralateral strength training.”

First observed in 1894, this phenomenon describes the increase in strength seen in an untrained limb of the body after strength training the opposite limb. For example, performing strength training exercises using the left arm has been shown to also induce an increase in strength in the right arm without working out the right arm at all. This effect can be seen in all different muscle groups in the body, in both males and females, and in people of all different ages. Researchers have hypothesized that high-force contractions used in resistance strength training can have a “spillover” effect on the neurons controlling the opposite limb. These neural circuits can carry motor output signals from the trained muscle to the untrained contralateral muscles which works to increase the electrical activity of the untrained muscle and effectively activate the muscle as if it were being trained as well. The video from the YouTube channel “House of Hypertrophy” helps illustrate this effect.

This video is from the YouTube channel “House of Hypertrophy” and helps illustrate the contralateral strength training phenomenon.

Harnessing the power of this neurophysiological phenomenon is key to injury recovery especially when one limb is immobilized for an extended period of time. It’s not just for competitive athletes either. Anybody with an injury can take advantage of contralateral strength training to dramatically speed up injury recovery. This can be especially useful for the elderly population where maintaining balance is an important factor of injury rehab. Imagine being able to maintain the strength and mobility of an elderly patient’s leg after a common surgery such as a knee replacement. Although the leg will be immobilized by a brace or a cast to keep the knee stable after surgery, it could be possible to prevent the muscles from atrophying by simply training the opposite leg with effective physical therapies. This could mean the difference between a smooth recovery versus one where the patient faces serious balance and stability issues as a result of a weakened limb that was immobilized in a cast for weeks to months at a time. Whether it be for injury recovery or specialized strength training, contralateral strength training has an amazing 2-for-1 effect in which the body’s own neural mechanisms allows both homologous muscles to experience the effect of a single unilateral training.

How Mice Could Help You Regenerate a Lost Limb

If you have ever experienced a nasty scrape or burn, you know the process of healing is not very fun. Human skin can take several weeks to regenerate after an injury and that often comes with a fair amount of pain. For a bigger injury that involves tissue damage, there is often little the human body can do to regenerate larger parts. However, thanks to a small rodent – the African spiny mouse – regenerative medicine for humans could be making huge advances in the near future.

The concept of regeneration is not something new in the animal world – we have seen creatures like salamanders regenerate lost tails and starfish regrow lost limbs. However, the African spiny mouse is the only mammal ever observed to be able to completely regenerate tissue such as skin, fur, hair follicles, sweat glands, and even cartilage. Being able to quickly shed skin caught in the mouths of large predators comes in handy for the mouse to be able to escape, but they must also be able to quickly heal those wounds.

African spiny mice in a research lab have spiny hair shown in (a) and (b). A skin wound was administered to a mouse in (c). Scabbing has occurred over the full injury as seen in (d) by Day 3. By Day 30, the original wound has healed and new hair follicles have been regenerated as seen in (e) and (f).
Figure 1. African spiny mice in a research lab have spiny hair shown in (a) and (b). A skin wound was administered to a mouse in (c). Scabbing has occurred over the full injury as seen in (d) by Day 3. By Day 30, the original wound has healed and new hair follicles have been regenerated as seen in (e) and (f). Source: Seifert, A., Kiama, S., Seifert, M. et al. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature 489, 561–565 (2012). https://doi.org/10.1038/nature11499.

How exactly does this happen? Researchers have found that the skin of the spiny mice is much weaker than that of most other mammals – think 20 times weaker than the skin of your regular old house mouse. Upon being handled, the skin is quick to shed leaving gaping wounds across the backs of these mice. This is due to the density of hair follicles found in their skin – a greater proportion of follicles means there is much less connective tissue to hold the skin leading to very easy tears. The weakness of the skin is contrasted by the rapidity by which it heals – the wounds can shrink to two thirds of their original size in a single day!

To understand a little bit more about the biomechanics of this process, we must look at how exactly the skin heals. As it turns out, collagen, the structural protein found in tissues which is responsible for skin elasticity among other things, is partly responsible for this phenomenon. Whereas mammals like you and I heal injuries through the generation of dense layers of collagen fibers aligned in parallel layers, these mice produce collagen fibers in crisscross networks that resemble the original makeup of tissue. This leaves the healed skin completely scar-free.

In addition, researchers have noted that ear wounds in the mice heal in a way similar to salamander tail regeneration. When a mouse’s ear gets injured, a ball of cells forms at the site of the wound that resembles cells in the embryonic state. This cell clump, called a blastema, is what allows the lost tissue to regrow on the ear. Scientists hope to use this information to study regeneration of tissue in humans.

An experiment was performed on both an African spiny mouse (Acomys) and another genus of rodents comparable to a house mouse (Mus) by making 4mm punctures in each species' ears. The size of the puncture was then observed over the following days showing that Acomys completely healed the ear puncture after 56 days while the size of the ear puncture in Mus remained relatively the same size showing no regeneration.
Figure 2. An experiment was performed on both an African spiny mouse (Acomys) and another genus of rodents comparable to a house mouse (Mus) by making 4mm punctures in each species’ ears. The size of the puncture was then observed over the following days showing that Acomys completely healed the ear puncture after 56 days while the size of the ear puncture in Mus remained relatively the same size showing no regeneration. Source: Matias Santos D, Rita AM, Casanellas I, et al. Ear wound regeneration in the African spiny mouse Acomys cahirinus. Regeneration (Oxf). 2016;3(1):52-61. Published 2016 Mar 9. doi:10.1002/reg2.50.

While there is still more research to do on the healing mechanism of the spiny mice tissue, the research done on these little mammals provides an excellent foundation for regenerative medicine for humans – something that studying regeneration in other animal species has not been able to accomplish. Being able to regenerate a lost limb was something once found only in science-fiction but could be a real possibility in the future.

Read More:

Insights into the regeneration of skin from Acomys, the spiny mouse

Optimal skin regeneration after full thickness thermal burn injury in the spiny mouse, Acomys cahirinus

Unique behavior of dermal cells from regenerative mammal, the African Spiny Mouse, in response to substrate stiffness

African spiny mice can regrow lost skin

Why your scar tissue isn’t an issue

What do knee scrapes, adolescent acne, and paper cuts have in common? They all have the potential to leave a nasty scar. For people who have undergone trauma that results in serious wounds, especially on the face, scar aging is a serious concern. What are scars, and why does scar tissue tend to look different than regular skin as aging occurs?

In 1861, Karl Langer began observing the nature of the skin’s tensile properties. He cut small, circular holes into cadavers, and looked to see where on these holes the skin pulled the most. From these experiments, he developed “Langer’s Lines,” which he asserted were lines of tension all around the human skin. Later, Borges noticed that Langer’s lines only applied to cadavers, and began to perform similar experiments on live people to see if he saw different results. He pinched the skin of live people, and then saw how the direction of pinching impacted the length of the wrinkle formed. From these experiments, he identified RSTL, or relaxed skin tension lines. More and more researchers after Langer and Borges investigated the “tension line” phenomena, and they all noticed the same thing: wounds cut across these lines always led to nastier, uglier scars than wounds parallel to the tension lines. Why would that happen?

Figure 1 outlines the differences of Langer's lines, Kraissl's lines, and Borges's RSTL on the human face.
Image courtesy of MedMedia

To answer this question, let’s first identify the cellular mechanisms at work during healing. According to David Leffell of the Yale School of Medicine, there are three key stages of scar formation. The first stage of scar formation is inflammation. This happens right after the wound is incurred. Blood flows to the site, and tissue called granulation tissue begins to form at the base of the wound. Next is proliferation, when that granulation tissue helps the surrounding fibroblast cells to duplicate as quickly as possible. Fibroblasts are very important; they are the cells that produce collagen, a key protein in tissue formation. During proliferation, more and more fibroblasts fill the site, and they begin rebuilding the collagen networks for new skin. The final stage of scar formation is maturation/remodeling, when fibroblast levels decrease slowly as fresh tissue is rebuilt.

This figure shows each stage of wound healing, as is outlined by the supporting paragraph.
Image courtesy of biodermis.com

Because scars are formed differently than regular skin, they also tend to age differently. Normal consequences of skin aging can be seen around us in older people every day. As you may notice in your parents and grandparents, older skin tends to be dry, rough, wrinkly, and sometimes discolored. While these changes can also occur within scar tissue, the biggest factor in scar tissue aging is the difference in the rate of skin cell renewal. Skin cell renewal occurs when new skin cells travel from the basal layer of the skin up to the epidermis. Scar tissue’s renewal rate is different than normal skin’s renewal rate. This is why adults recover from wounds more slowly than young people – there is a greater difference between their cell renewal rates. The age at which the scar was formed, and the quality of the care provided, are critical in evaluating how well the scar will age.

If you’re interested in learning more about how that cut on your hand might heal and age, watch this video from TED-Ed, or for more detailed reading, check out this article.

Ankle Sprains: An Epidemic in the World of Athletics

Have you ever been out running on a gorgeous fall day, only to have the run cut short by a painful misstep on a tree root covered by leaves? I have, and let me tell you – it’s awful! And even if you aren’t a runner, according to the Sports Medicine Research Manual, ankle sprains are a common, if not the most common, injury for sports involving lower body movements. Now, the solution to preventing this painful and annoying injury could be as simple as avoiding tree roots and uneven ground, but the real problem behind ankle sprains deals with the anatomy of the ankle.

The ankle is made up of many ligaments, bones, and muscles. However, when sprained, it is the ligaments that are mainly affected. Connecting bone to bone, ligaments are used to support and stabilize joints to prevent overextensions and other injuries. The weaker a ligament is, the easier it is to injure. There are three main lateral (outer) ligaments supporting the ankle joint that can become problematic: the anterior talofibular ligament, the calcaneofibular ligament and the posterior talofibular ligament. According to a study from Physiopedia, these lateral ligaments are weaker than those on the interior (medial) of the ankle, with the anterior talofibular ligament being the weakest.

An image depicting the various ligaments of the ankle, both lateral and medial.
Anatomy of the ankle, highlighting the lateral and medial ligaments

The next question that has to be asked is why are these ligaments so much weaker than other ones? The answer to this question is based on their physical make up. Ligaments are made of soft tissue that has various collagen fibers running parallel to each other throughout it. The more fibers there are, the more structure and rigidity there is. Think of the fibers as a rope: The rope can stretch to a certain point, but once it hits that point it will snap and break. But if you have a thicker rope (such as the medial ligaments), it becomes much harder to break.

The ligaments on the outer part of the ankle have fewer collagen fibers than those on the inside of the ankle. Thus, when the ankle is moved in an awkward position, it is more likely that the lateral ligaments will break.

Once you sprain your ankle, the focus turns to treatment. Treatment will differ slightly for every individual depending on the severity of the ankle sprain. The simplest way to treat a sprained ankle is to follow the RICE (Rest, Ice, Compression, Elevation) method. Other forms of treatment include taping the ankle or using a brace to restrict movement and to add support and extra stability. Wearing proper footwear is another way that one can prevent and help treat a sprained ankle, as certain shoes are specifically designed to help avoid such injuries. To prevent future ankle sprains, exercises are recommended to help strengthen and stabilize the joint and surrounding ligaments and muscles.

For more information on ankle anatomy and sprains, check out these articles on BOFAS and SPORTS-Health.

Why do bone fractures take a long time for healing?

An athlete walking on crutches across the field - from The Washington Post
An athlete walking on crutches across the field – from The Washington Post

Have you observed that someone around you has broken their arms or legs? Bone fracture is a complete or incomplete break of bone continuity. And it is very common in our daily lives that there are more than 3 million cases in the U.S. per year. Many events may cause bone fractures, such as falls, car accidents or sports injuries. So, do you know how long it takes for the fracture to heal?

Locking compression plate used for treatment of a proximal femoral fracture - by Bjarke Viberg on ResearchGate
Locking compression plate used for the treatment of a proximal femoral fracture – by Bjarke Viberg on ResearchGate

Bone fracture healing is a repair process that consists of multiple stages. There are two types of repair: primary and secondary bone healing. Primary healing only occurs with the application of rigid internal fixation, for example, a compression plate. The rigid fixation provides absolute stability, and primary healing includes attempting to reconstruct the continuity between fracture fragments.

In contrast, secondary healing occurs when the fixation is not rigid. For secondary healing, there are four stages: inflammatory response, soft callus formation, hard callus formation, and bone remodeling. After the bone fracture, torn vessels form hematoma, which is localized bleeding outside of blood vessels within the fracture site and provides a foundation for the following stages. The inflammation begins immediately and continues until the cartilage or bone begins to form. During the inflammatory phase, stem cells migrate to the fracture site, form the granulation tissue (new connective tissue and microscopic blood vessels), and release growth factors that stimulate bone formation. This phase usually lasts 3-4 days and may last up to one week.

In the second week after the bone fracture, soft callus (cartilage) begins to form. At this stage, cells within periosteum (the membrane covers the outer surface of the bone) and granulation tissue begin to proliferate and differentiate into chondrocytes until they bind with each other. Chondrocytes are the cells found in cartilage connective tissue and constitute the “bridging callus”. In addition, the amount of newly formed cartilage is related to stability, that less stability leads to more cartilage. The formation of soft callus will be completed within the first three weeks after the fracture, which means this phase needs approximately two weeks to complete.

The following stage is hard callus formation, also known as endochondral ossification. It is a replacement of cartilage with bone. Mineralization of cartilage develops from the ends to the center of the fracture site. The trabecular bone would be formed from osteoblasts (cells that synthesize bone tissue) on the newly exposed mineralized surface. Finally, all the cartilage turns into trabecular bone and forms the “hard callus”. At the end of this phase, the injured bone will be able to recover sufficient strength and rigidity for rehabilitation exercise.

4 stages of secondary fracture healing. Stage 1: Inflammatory response. Stage 2: Soft callus formation. Stage 3: Hard callus formation. Stage 4: Bone remodeling - from Bigham-Sadegh & Oryan, International Wound Journal 2014
4 stages of secondary fracture healing. Stage 1: Inflammatory response. Stage 2: Soft callus formation. Stage 3: Hard callus formation. Stage 4: Bone remodeling – from Bigham-Sadegh & Oryan, International Wound Journal 2014

The final stage of secondary bone healing is bone remodeling. This phase starts 3-4 weeks after the bone fracture. Bone remodeling is a slow process that may last 6-9 years, which is 70% of the total healing time. In the remodeling, osteoclasts (cells that break down bone tissue) resorb the trabecular bone, and osteoblasts deposit compact bone. It is a process of equilibrium between resorption and formation, that the trabecular bone is replaced by compact bone, in order to recreate the bone to appropriate shape and adapt to mechanical loads and strain.

In clinical treatment, bone fracture usually takes 6-8 weeks to heal. However, it does not mean the bone is totally cured. When the doctor says the treatment is finished and it is fine to let the body free from the fixation, the bone actually is at the beginning of the final stage since the bone remodeling may take several years.

For more details of the bone fracture healing, please check the following video:

For further reading, please click here and here.

Skeletal Support Seekers’ Success (So Far)

Bones break, and broken bones need time to heal, or regrow. Fans of J.K. Rowling’s Harry Potter series are quite familiar with the concept of bone repair, as Harry is once required to drink a Skele-Gro potion to magically (and painfully) regrow his arm bones overnight. Now, as fantastic as it would be to completely fix broken bones in a few hours, modern medicine has not yet discovered that secret of the Wizarding World; however, several treatments have been developed in attempts to speed the rate of fracture repair as well as increase the comfort of the patient (take that, Skele-Gro).

Images of a broken bone and the progression of a callus being formed over time
Image from Cambridge Fracture Clinic

For those unfamiliar with the process of bone repair, a quick overview is in order. In short, inflammation provides stability to a fractured area, and over the course of several weeks fibrous tissue forms a callus around the fracture which is eventually replaced by bone. The mechanical environment at the fracture site is influential in healing, with factors such as hormones, vitamins, minerals, diet, fluid flow, and physical and electrical stimuli affecting healing rates. With these factors in mind, engineers and scientists are attempting to speed bone regrowth.

Low-level laser therapy (LLLT) is one practice found to accelerate bone healing. A study published in Lasers in Medical Science revealed that LLLT stimulates bone cells in fracture areas which increases the rate of callus development. Tests performed on the broken tibial bones of two groups of white rabbits demonstrated that bone mineral density at fracture sites remained higher in the group receiving laser therapy than in the control group throughout healing. 

However, post-mortem tests revealed that bones healed under LLLT endured significantly lower maximum stresses than intact bones or bones healed under normal conditions. This is a controversial result, as other studies have concluded opposite findings, so despite the enhanced growth resulting from LLLT, the authors of this study agree that additional experiments are necessary to satisfactorily settle this issue.

Images of stress concentrations in and around a solid titanium implant and porous titanium implants with various levels of bone ingrowth
Modified from Spoerke, et al., Septermber 2005

Surgical implants are another device used to facilitate bone healing. Most bone implants are made of titanium due to its lightness, durability, and biocompatibility. While these supports effectively immobilize and position bones for proper healing, some patients experience complications later on, largely due to stiffness differences between bone and titanium—resulting stress concentrations increase risk of fracture or implant loosening. Titanium foam implants coated in an organoapatite (OA) layer are a developing solution to this issue, described in detail in an Acta Biomaterialia article.

The porous surface of titanium foam, studied in vitro, substantially decreases implant stiffness, thus enabling stress to be more evenly shared between the foam and surrounding bone. Allowing bone ingrowth into the pores also reduces stress concentrations at the materials’ interface which helps alleviate risk of implant failure. Furthermore, the OA coating on the foam stimulates bonding between bone tissue and the implant, thereby increasing stability. The success of these studies suggest that titanium foam is ready for in vivo testing. 

Check out this video on the advantages of titanium foam:

Although the results of these fracture repair treatments are still a far cry from those achieved with Skele-Gro, further research and development regarding bone regrowth may lead to significant advances in the very near future. Interested in learning more? Check out articles on other developing fracture treatment technologies here and here.