Tag: orthopaedics

Discovery of New Skeletal Tissue Holds Promise for Regenerative Medicine

“Lipocartilage” is a type of supportive skeletal tissue, that consists of densely packed, bubble-like cells containing fat. This image shows a scan of mouse ear lipocartilage stained with a green fluorescent dye. Charlie Dunlop School of Biological Sciences

An international research team led by the University of California, Irvine has discovered a new type of skeletal tissue that offers great potential for advancing regenerative medicine and tissue engineering.

Most cartilage relies on an external extracellular matrix for strength, but “lipocartilage,” which is found in the ears, nose and throat of mammals, is uniquely packed with fat-filled cells called “lipochondrocytes” that provide super-stable internal support, enabling the tissue to remain soft and springy – similar to bubbled packaging material.

The study, published in the journal Science, describes how lipocartilage cells create and maintain their own lipid reservoirs, remaining constant in size. Unlike ordinary adipocyte fat cells, lipochondrocytes never shrink or expand in response to food availability.

“Lipocartilage’s resilience and stability provide a compliant, elastic quality that’s perfect for flexible body parts such as earlobes or the tip of the nose, opening exciting possibilities in regenerative medicine and tissue engineering, particularly for facial defects or injuries,” said corresponding author Maksim Plikus, UC Irvine professor of developmental and cell biology. “Currently, cartilage reconstruction often requires harvesting tissue from the patient’s rib – a painful and invasive procedure. In the future, patient-specific lipochondrocytes could be derived from stem cells, purified and used to manufacture living cartilage tailored to individual needs. With the help of 3D printing, these engineered tissues could be shaped to fit precisely, offering new solutions for treating birth defects, trauma and various cartilage diseases.”

Dr Franz Leydig first recognised lipochondrocytes in 1854, when he noted the presence of fat droplets in the cartilage of rat ears, a finding that was largely forgotten until now. With modern biochemical tools and advanced imaging methods, UC Irvine researchers comprehensively characterised lipocartilage’s molecular biology, metabolism and structural role in skeletal tissues.

They also uncovered the genetic process that suppresses the activity of enzymes that break down fats and reduce the absorption of new fat molecules, effectively locking lipochondrocytes’s lipid reserves in place. When stripped of its lipids, the lipocartilage becomes stiff and brittle, highlighting the importance of its fat-filled cells in maintaining the tissue’s combination of durability and flexibility. In addition, the team noted that in some mammals, such as bats, lipochondrocytes assemble into intricate shapes, like parallel ridges in their oversized ears, which may enhance hearing acuity by modulating sound waves.

“The discovery of the unique lipid biology of lipocartilage challenges long-standing assumptions in biomechanics and opens doors to countless research opportunities,” said the study’s lead author, Raul Ramos, a postdoctoral researcher in the Plikus laboratory for developmental and regenerative biology. “Future directions include gaining an understanding of how lipochondrocytes maintain their stability over time and the molecular programs that govern their form and function, as well as insights into the mechanisms of cellular aging. Our findings underscore the versatility of lipids beyond metabolism and suggest new ways to harness their properties in tissue engineering and medicine.”

Source: University of California – Irvine

Prehabilitation Improves Orthopaedic Surgery Outcomes

Photo by Barbara Olsen on Pexels

Pre-surgery exercise and education, or ‘prehabilitation’, can significantly improve outcomes for patients undergoing orthopaedic surgery, according to new research published in JAMA Network Open.

An ageing population plus the COVID pandemic has put great strains on healthcare systems, creating a longer waiting time for patients due to undergo routine elective surgical procedures. This can cause mental and physical deconditioning in patients, potentially impacting their surgical outcomes.

The study found prehabilitation may mitigate these negative factors and assist in improving strength and function prior to a surgical intervention. This may include exercise, patient education, pain management and psychological support.

Researchers from Anglia Ruskin University (ARU), Addenbrooke’s – Cambridge University Hospitals NHS Foundation Trust (CUH) and Western University in Ontario, Canada, examined the results of 48 unique clinical trials involving prehabilitation techniques such as exercise, pain management and acupuncture among patients about to undergo orthopaedic surgery.

Outcomes were measured prior to surgery as well as at intervals post-operation. Results were graded for certainty, or confidence that results were true.

Prior to surgery, the study found strong evidence that prehabilitation led to a reduction in back pain for people waiting for lower back surgery and evidence of moderate certainty for improvement in their health-related quality of life.

For patients waiting for total knee replacement, evidence of moderate certainty showed prehabilitation improved function and muscle strength. For patients waiting for a total hip replacement, evidence of moderate certainty showed prehabilitation improved health-related quality of life and hip muscle strength.

Following an operation, the study found that prehabilitation improved function in the short to medium term compared with no prehabilitation. In particular, evidence of moderate certainty suggested prehabilitation had favourable outcomes on function in those who had undergone knee replacement surgery at six weeks post-operatively. Evidence of moderate certainty also suggests prehabilitation improved function six months after lower back surgery.

Lead author Anuj Punnoose, ARU PhD candidate and Clinical Specialist Physiotherapist at CUH, said: “This study stemmed out of a need to find the best ways to prepare orthopaedic patients prior to surgery and prevent them from further deconditioning. Furthermore, any prehabilitation programme should ideally be delivered for at least four to six weeks prior to the surgical intervention and twice a week for optimum results. Health services looking at developing such programmes could utilise recommendations from this study.”

Source: Anglia Ruskin University

Unique Genetic Profile of Bone Cells Mapped

X-ray of a wrist. Photo by Cara Shelton on Unsplash

Pioneering new research has charted the unique genetic profile of the skeleton’s ‘master regulator’ cells, known as osteocytes.

The study led by the Garvan Institute of Medical Research was published in Nature Communications. The study describes the genes that are switched on or off in osteocytes, a multifunctional type of bone cell that regulates how bone material is grown or broken down in order to maintain healthy skeletons.

“This new information provides a kind of genetic shortlist we can look to when diagnosing bone diseases that have a genetic component,” said the study’s first author Dr Scott Youlten, Research Officer in the Bone Biology Lab. “Identifying this unique genetic pattern will also help us find new therapies for bone disease and better understand the impacts of current therapies on the skeleton.”

Far from static, the skeleton is a highly dynamic structure that is constantly remodelled throughout a person’s life. Though osteocytes are the most common cell type in bone, they have been hard to study as they are embedded within the skeleton’s hard mineral structure.

Osteocytes form a network inside bones on a scale and complexity which mirrors the neurons in the brain (42 billion osteocytes with over 23 trillion connections between them), which monitors bone health and responds to ageing and damage by signalling other cells to either add more bone or break down old bone. Osteoporosis, rare genetic skeletal disorders and other bone diseases arise from an imbalance in these processes.

To understand what genes are involved in controlling bone build-up or breakdown, the researchers isolated bone samples from different skeletal sites of experimental models in order to measure the average gene activity in osteocytes. In so doing, they found an osteocyte ‘signature’ of 1239 genes that are switched on. Of these genes, 77% had no previously known role in the skeleton, and many were completely novel and unique to osteocytes.

“Many of the genes we saw enriched in osteocytes are also found in neurons, which is interesting given these cells share similar physical characteristics and may suggest they are more closely related than we previously thought,” explained Dr Youlten.

Comparing the osteocyte signature genes with human genetic association studies of osteoporosis could identify new genes that may be associated with susceptibility to this common skeleton disease. Additionally, a number of these osteocyte genes were also shown to be responsible for rare bone diseases.

“Mapping the osteocyte transcriptome could help clinicians and researchers more easily establish whether a rare bone disease has a genetic cause, by looking through the ‘shortlist’ of genes known to play an active role in controlling the skeleton,” said Dr Youlten.

Co-senior author Professor Peter Croucher, Deputy Director of the Garvan Institute and Head of the Bone Biology Lab, said that “the osteocyte transcriptome map gives researchers a picture of the whole landscape of genes that are switched on in osteocytes for the first time, rather than just a small glimpse”.

“The majority of genes that we’ve found to be active within osteocytes had no previously known role in bones. This discovery will help us understand what controls the skeleton, which genes are important in rare and common skeletal diseases and help us identify new treatments that can stop development of bone disease and also restore lost bone.”

Source: Medical Xpress

Journal information: Nature Communications (2021). DOI: 10.1038/s41467-021-22517-1