Craniofacial regeneration
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Craniofacial regeneration refers to the biological process by which the
Function
Craniofacial regeneration is necessary following injury to the facial tissue. This can occur during surgery, where doctors fracture the face of a patient in order to correct
Craniofacial defects are most common
Most patients who suffer from
Research and historical context
In the 1970s,
Stem cells
While there is a lack of craniofacial-specific
Bone marrow mesenchymal stem cells (BMMSC)
Adipose-derived mesenchymal stem cells (AMCs)
Mechanism & Important Factors
Following facial tissue injury, craniofacial regeneration occurs in a sequence of steps. The process of regeneration is initiated by an
Inflammation
During
Angiogenesis and VEGF
Angiogenesis allows for
VEGF has two known roles in bone regeneration: promotion of
In addition, VEGF is necessary for a specific bone regeneration pathway called intramembranous ossification, where mesenchymal tissue is directed towards bone formation. This involves the direct differentiation of bone progenitors to osteoblasts (contrary to a cartilage intermediate in endochondral ossification). Many primary literature papers have demonstrated that a loss-of-function experiment against VEGF in the osteoblast precursors significantly reduces ossification in craniofacial bone structures,[27][28][29] highlighting the essential role of VEGF in craniofacial regeneration.
Mesenchymal Stem Cells (MSCs)
Osteogenic tissue is
Undifferentiated MSCs are limited in adults, but these cells along with committed osteoprogenitor cells are both involved in callus formation. Along with MSCs and osteoprogenitors, mechanobiology also influences bone regeneration. Simply put, compression can enhance bone apposition.[32] This is known as Wolff's law, which essentially states that bone remodeling occurs to counter and adapt to loads placed upon it.[31]
Scientific understanding of bone regeneration in vitro is limited. Thus, in vivo assays have been explored. One such assay is the “gold standard” assay, created by A.J. Friedenstein. His test utilizes diffusion chambers (open system) in which he implanted MSCs into immunodeficient mice. When this was done, he observed that MSCs formed bone and bone marrow. His test has also been used to demonstrate self-renewal and maintenance of “stemness” in serial implantations.[31]
Healing Process
One week following injury there are two
Nerve Regeneration
Following facial injury it is also critical to restore
Experimental models
Current approaches to craniofacial research are spearheaded by a branch of the U.S. National Institutes of Health, named the National Institute of Dental and Craniofacial Research (NIDCR). With regards to regenerative medicine, the NIDCR invested $52 million in “basic, translational, and clinical” regenerative research in 2017.[39] These experiments include but are not limited to:
- Microengineering blood vessels: enhancing current engineering of nutrient-rich blood vessels to promote transplanted tissues and bone precursor cells (cells that will give rise to bone structure). Proper engineering of these circulating blood vessels would alleviate pressure on newly implanted cells or craniofacial structures.
- Designing stronger cartilage: challenging cartilage cells in vitro (in the laboratory) with harsh conditions to mimic the environment of a craniofacial defect. It is vital that laboratory-generated cartilage be comparable in strength to natural cartilage.
- Isolating bone stem cells: purifying stem cells from a collection of human fat tissue that can generate bone in vivo (animal models).
Researchers are also implementing many genetic tools to further understand craniofacial regeneration. Developmental biologists have been reported to use laser capture microdissection and fluorescence-activated cell sorter (FACS) to create an array of genes involved in craniofacial development.[40]
Identification of specific genes necessary in craniofacial development can lead to striking transgenic experiments. These types of procedures involve genetically editing organisms to understand the function of their genes. For example, using Cre-recombinase, an enzyme which makes specific cuts in the genome, researchers were able to knockout the expression of Sp8, a gene hypothesized to be essential for face development. In the resulting mouse model, it was observed that facial development was significantly impaired, yet a tongue and a mandible were present (see image).[40] Transgenic animal models is just one way in which researchers are attempting to understand craniofacial abnormalities.
Causes of craniofacial injury
Physical injury
These injuries happen predominantly in young males, often as a result of traffic accidents which result in 22% of all craniofacial trauma. Craniofacial injuries can result in death due to
The usual surgery used to treat severe craniofacial injury occurs in three stages. Craniotomy is performed immediately, followed by orbitofacial repair 7–10 days later and finally cranioplasty after 6–12 months.[37]
Genetic disorders
Treacher Collins syndrome
Cherubism
Stickler syndrome
Surgery
This section may require cleanup to meet Wikipedia's quality standards. The specific problem is: limited coverage of surgeries for CF regeneration, poorly referenced. (December 2019) |
Facial surgery is often voluntary to make features more aesthetically pleasing. Rhinoplasty is exceedingly common, with 220,000 procedures occurring each year.[43] They are used for improving the outward appearance of the nose and for improving nasal airway flow. The first step is an incision into the columella, the skin connecting the nostrils. Surgeons can then remove cartilage and bone to correct a dorsal hump, wide tip, or crooked nose. They are also able to correct deviated septums, which are a common airway blockage. Once this is completed, the incisions are closed and splits are placed to maintain stability during the healing process.[45] Aesthetic surgery is also common following tumor resections, where plastic surgeons correct soft tissue or bone misalignments that occurred due to the removal of a tumor. These procedures can involve bone grafts from the pelvis or ribs to replace removed bone and implantation of titanium plates and screws to hold pieces of bone together.
References
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