Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
A hydrogel injection to regenerate cartilage

A hydrogel injection to regenerate cartilage

3D BioPen: a hydrogel injection to regenerate cartilage - developmental path towards clinical treatment
Development of BioPen. Credit: Biofabrication, doi: https://doi.org/10.1088/1758-5090/aad8d

Highly specialized cartilage is characteristically avascular and non-neural in composition with low cell numbers in an aliphatic environment. Despite its apparent simplicity, bioengineering regenerative hyaline cartilage in a form effective for implantation remains challenging in musculoskeletal tissue engineering. Existing surgical techniques including autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are considered superior to self-repair induction techniques. However, both MACI and ACI are complex, multistage procedures that require a double operation; first for surgical excision of native cartilage, followed by expansion of adult chondrocytes in vitro prior to implantation by a second operation.

Regenerating robust articular hyaline-like cartilage is a key priority in musculoskeletal tissue engineering to prevent cost-intensive degenerative osteoarthritis that limits the quality of life in global healthcare. Integrating mesenchymal stem cells and 3-D printing technologies has shown significant promise in bone tissue engineering– although the key challenge remains in transferring the bench-based technology to the operating room for real-time applications. To tackle this, a team of Australian orthopedic surgeons and bioengineers collaboratively proposed an in situ additive manufacturing technique for effective cartilage regeneration. The handheld engineered extrusion device known as the BioPen offers an advanced, co-axial extrusion strategy to deposit cells embedded in a hydrogel material within a surgical setting. The dynamics of material distribution to facilitate cell survival, and the maintenance of mechanical properties for cartilage tissue engineering of BioPen are now published in Biofabrication, IOP Science.

In the recent study, Claudia Di Bella and co-workers conducted neocartilage biofabrication as a requisite step in the path toward clinical translation of the BioPen device, preceded by an in vivo proof-of-principle pilot animal study performed in a sheep model. The authors used human adipose-derived mesenchymal stem cells (hADSCs) laden in gelatin methacrylate (GelMa) and hyaluronic acid methacrylate (HAMa) hydrogels, extruded via the BioPen to generate bioscaffolds that formed hyaline-like cartilage. The authors replicated the previously established protocol to synthesize the GelMa/HAMa hydrogel. The surgical device showed capacity to biofabricate a regenerative stem cell niche in situ with future potential to change the existing clinical approaches in surgical practice for organ and tissue regeneration.

The bench to clinic framework of materials development for clinical translation of the BioPen device. The flow chart lists the steps achieved (green) and the steps projected (purple). The present stage is neocartilage biofabrication (red highlight), this is the final step for in vitro analysis, prior to ex vivo and in vivo animal studies. Credit: Adapted from Biofabrication, doi: 10.1088/1758-5090/aad8d

Human stem cells were harvested from the infrapatellar fat pad (IPFP) of patients undergoing total knee replacement. To control the size and shape of the scaffolds extruded by the BioPen, the authors used polydimethylsiloxane (PDMS) cylindrical molds to create a desired shape with regulated cell numbers, providing reproducible structural organization with 3-D geometry for mechanical testing. Immediately after extrusion, samples were irradiated with UV light for photopolymerization. Materials were characterized with mechanical loading tests for compression and atomic force microscopy (AFM) to determine surface topology.

The capacity to produce hyaline-like neocartilage was analyzed using the cellular response to the chondrogenic stimuli via histology, gene and protein expression analysis. The building of new tissue was defined by protein localization and organization of the main components of hyaline cartilage. The neocartilage function was determined via mechanical properties with time.

The study demonstrated the capacity of the BioPen to produce human hyaline-like cartilage by coaxial extrusion of hADSC-laden in GelMa/HAMa hydrogel. A handheld device for surgical extrusion can also overcome clinical graft-site mismatch limitations. The previously established core/shell distribution of the scaffold geometry protected the survival and proliferative potential of the hADSCs. Genes expressed during hyaline-like cartilage formation were quantified with qRT-PCR, the expression of SOX9 – the master regulator of chondrogenesis reflected the chondrogenic potential of the stem cells source. Cells similarly expressed COL2A1 (type II collagen found in cartilage) and ACAN (that forms proteoglycan protein) to demonstrate differentiation. Bioscaffolds were further tested using non-linear two-photon microscopy and second-harmonic generation (SHG) to detect mature fibrillary collagen after eight weeks of chondrogenesis.

Extruding gel with UV light for photopolymerization. Credit: Melbourne Medical School, Biofabrication, doi: 10.1088/1758-5090/aad8d

The possibility of delivering osteogenic and chondrogenic growth factors within the hydrogel will be considered in the future. Additional studies will also aim to achieve biomechanical properties for the chondrogenic bioscaffolds comparable to native articular cartilage. Studies hereon will evaluate de novo cartilage formation to understand the interplay between stem cells and 3-D architectured hydrogels with different mechanical and biodegradation properties.


Explore further:
Platelet-rich plasma does not promote stem cell-mediated cartilage repair

More information:
Carmine Onofrillo et al. Biofabrication of human articular cartilage: a path towards the development of a clinical treatment, Biofabrication (2018). DOI: 10.1088/1758-5090/aad8d9

Serena Duchi et al. Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair, Scientific Reports (2017). DOI: 10.1038/s41598-017-05699-x

Cathal D O’Connell et al. Development of the Biopen: a handheld device for surgical printing of adipose stem cells at a chondral wound site, Biofabrication (2016). DOI: 10.1088/1758-5090/8/1/015019

Journal reference:
Biofabrication

Scientific Reports

About author

Related Articles