Regenerative and reconstructive
medicine
LECTURE 1: INTRODUCTION
There are numerous clinical situations where tissue or organs are
damaged to such an extent that repair or regeneration is necessary. These
include trauma, ageing and congenital disorders. —> solution
transplantation or reconstructive surgery.
Autograph (golden standard): within one patient, fast healing, no rejection
problem or disease transmission, multiple surgical sites, limited treatment
at one hand, shortage (example very old person)
Allograft: from donor or acceptor, no second surgical site, short procedure,
risk of rejection by the body, longer healing and incorporation, shortage.
Shortage:
In donor organs: kidneys, liver, heart, lungs, small intestine
In donor tissue: cornea, heart valves, ski, bones, tendons, cartilage, large
vessels
Around 150 patients die while waiting for a donation.
Transplant medicine
Xenograft
From animal to human
Unlimited supply, no second surgery
Possible rejection or failure to incorporate with the body, longer healing
Alloplastic graft
Synthetically derived or made from natural
Low risk of disease transmission and low antigenicity
“Dead” materials —> poor integration
Tissue engineering
Introduced in 1980s-1990s
Tissue engineering is an interdisciplinary field that combines
biology, engineering, and materials
science to develop artificial biological
tissues that can replace or repair
damaged tissues.
Its ultimate aim is to restore,
maintain, or improve tissue function.
,Both solution and problem come from the patient.
1. Three-dimensional cell carrier material
“scaffold” (e.g. collagen sheet, biopolymer
porous foam, hydrogels)
2. Living cells (primary from a patient or
animal, embryonal /iPS / adult stem cells)
3. Additional factors specific for the cell type
or for proper tissue development (e.g.
growth factors, cytokines, bioreactors)
Most successful TECs so far is achieved in supporting tissues:
Skin
Bone/cartilage
Cardiovascular tissues
Useful tools for research
Drug development
Replacement of some animal Studies
Introduced in mid 2000s’
Broader than TE
, Tissue self-healing with help of foreign biological signals
Drug delivery
Stem cell therapy
Gene therapy, incl. mRNA delivery
Theranostics: therapeutic + diagnostics
TE & RM are often interchangeable terms
Replacement —> regeneration
• Replacement
Partly functional replacement of diseased or damaged tissues or orangs,
usually without replication of natural structure (prostheses, artificial
organs, most grafts)
• Regeneration
Generation of new tissue that is functionally and structurally analogous to
the diseased or damaged tissues or organs
, Wound healing questions:
1. Orientation and Diameter of Collagen Fibrils in Normal Dermis vs. Scar
Tissue:
In normal dermis, collagen fibrils are organized in a basket-weave
pattern, allowing for flexibility and strength. The fibrils are relatively
uniform in diameter.
In scar tissue, collagen fibrils are often more disorganized, aligning
in parallel bundles. The fibrils tend to be thicker, and the scar tissue
generally lacks the flexibility of normal skin due to this altered
structure.
2. Major Mechanistic Difference Between Fetal and Adult Wound Healing:
Fetal wound healing occurs with minimal inflammation and does
not result in scar formation. This is due to higher levels of growth
factors like TGF-β3, reduced inflammatory response, and an
enhanced ability to regenerate tissue.
Adult wound healing typically involves a more pronounced
inflammatory response and often results in scar formation, with
higher levels of TGF-β1 and TGF-β2 promoting fibrosis.
3. Two Major Disadvantages of Skin Repair Compared to Skin
Regeneration:
Loss of original structure and function: Repaired skin often has
scar tissue, which lacks the normal architecture and flexibility of the
original skin.