How to minimise fat cell death post fat grafting that your surgeon won't tell you (2 Viewers)

[surgerymax]

Periorbital fat grafts are an affordable , very effective treatment to improving the eye area , there’s a good case to be made to even opt for this instead of implants.​

The main big issue with fat grafts is the survival rate and it’s particularly brutal in the peri orbital area (30-80% survival rate) , it’s common to overfill to try compensate for the fact you will lose significant fat however you can only do this to a certain extent before overfilling actually starts to cause more fat loss , this happens due to parcels of fat forming that are further from blood supply that will die (this kind of overfilling is a major cause for massive fat loss)

There is a 2mm rule Adipocytes within a 2mm range from the graft edge can receive sufficient nutrition through early neovascularization and survive , anything deeper than 2mm from the graft surface is essentially in an ischemic core
Even will overfilling correctly if you aren’t fortunate you will just see so much of the fat melt away
Beyond things like the obvious surgeon technique , managing by weight post op what else can be done to make fat grafts more likely to survive , first need to look into the route cause of the fat cell death
This being
1. Poor blood supply (sufficient blood supply is needed to restore nutritional support, transmit stem cells, and reduce oxygen deficit)
2. Mechanical stress
3. Oxidative stress/Inflammation
We can use a pharmaceuticals stack that promotes adipogenesis , blood flow and more to try counteract this as much as possible , of course your surgeon won’t tell you this as it loses them money when you don’t come back for a revision , there's a good chance they're also just as unaware JFL.
Most of these have minimal human data with mostly preclinical data however there is strong mechanistic plausibility for all as well as most being healthmaxxes in general so i see 0 reason not to run this

Vitamin E + Pentoxifylline​

I'm not going to waste time explaining the mechanisms of the actual drugs , this is dedicated to their application to fat grafting survival specifically


In this study they had recorded the effects of vitamin E and Pentoxyfilline on fat grafted mice (human fat grafted to them) and the drugs were actually administered orally

Vitamin E had showed significant effects in fat retention due to its reductions in oxidative stress and angiogenesis , surprisingly pentoxifylline did not but there is still good mechanistic reasoning to use pentoxifylline post fat grafting

This is because pentoxifylline increases red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation
In the context of fat grafting this matters because capillaries in that region are small and blood flow is compromised.
As RBCs become more flexible and plasma less viscous this increases oxygen delivery to the marginal zone of the graft where cells are on the edge of survival.

Vitamin E was effective through reducing oxidative stress and its effects on angiogenesis (forming of new blood vessels)

These are rough estimates but when you scale for humans the dosage of pentoxifylline used was 8mg/kg , which is quite low (560mg for a 70kg male) , in real world 1200mg ED is common so we can go far above this dose in the study
The vitamin E was 0.9mg/kg60-65mg for a 70kg male which is still much lower than what you could run

PDE5 inhibitors​

PDE5 inhibitors improve the vasodilatory effect of NO through cGMP and have demonstrated beneficial effects in angiogenesis endothelial proliferation , remodelling and improvement of oxygen supply during healing.
They can also regulate vasodilation and clear oxidative stress components


Of all PDE5 inhibitors, tadalafil has the longest half-life at 17.5 hours making it the most practical for sustained perioperative coverage


This has some interesting data behind it though unfortunately is only in rodents and done in a way that isn't practical for us (method is patent protected and could be annoying to convince your surgeon regardless) though systematic PDE5 inhibitors are still is powerful.

A patent protected method demonstrates that PDE5 inhibitor treatment of grafts prior to harvest and transfer significantly improved revascularisation within the graft core at 1 and 2 weeks post grafting with sildenafil treated grafts maintaining virtually ALL volume over 12 weeks compared to rapid resorption in controls

As you can see the group with sildenafil not even tadalafil maintained pretty much double the fat
Of course this effect wouldn’t be near as profound practically when we use systematic PDE5 inhibitors rather than it being injected right into the subq fat as in this study however you will still get the benefits such as cGMP pathway enhancement , vasodilation , microcirculatory improvement , angiogenic signalling modulation and more.

BPC-157​

This one is mainly mechanistic speculation though should hold up and is worth adding IMO


'It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions'

Rapamycin​

Rapamycin is quite interesting for fat cell preservation

mTOR inhibition by rapamycin upregulates autophagy (the cellular self cleaning process)

In a fat graft context this is relevant because grafted adipocytes in the ischaemic zone (area lacking blood flow) are energy starved.
They can't access external nutrients or oxygen adequately due to lack of blood flow.
Autophagy allows these cells to essentially use their own damaged components to survive the ischaemic window until revascularisation occurs

There is actually some pretty recent direct fat graft research on this published in 'Aesthetic Plastic Surgery'

​

The timing logic here is important autophagy upregulation during the first 72 hour ischaemic window which can extend how long cells survive before vessels reach them

However mTOR is also required for normal adipogenesis and adipocyte differentiation , sustained mTOR inhibition could impair the regenerative replacement phase that follows initial survival

Rapamycin might be beneficial acutely in the ischaemic window but counterproductive during neovascularisation and onward , essentially only use during the first 72 hours post fat grafting.

Bonus : Botox​

Threw this one in as a bonus just because i found it interesting tbh though I imagine most people wont bother with doing this but Botox not only does it help promote angiogenesis through many mechanisms but is the first on this list to directly reduce mechanical stress which is another major factor , there isn't much data but has a lot of potential to work.

PPARY agonists​

PPARY agonists might seem like an obvious choice as it is the ‘master transcription factor for adipogenesis however they strongly promote adipogenesis in preadipocytes, but in mature adipocytes rosiglitazone actually decreases lipid content rather than increasing it.

Meaning do not use them though on paper it would seem like a no brainer

LDN (Low Dose Naltrexone)​

Naltrexone at any dose is a TLR4 antagonist
TLR4 is a pattern recognition receptor on macrophages and other immune cells that gets activated by free fatty acids and lipid debris from lysed adipocytes
When adipocytes lyse (break) in the graft they release free lipid droplets that activate TLR4 on macrophages triggering a sustained inflammatory response that damages neighbouring cells.
LDN blocking TLR4 directly interrupts this specific pathway.

Antioxidant stack ​

It is very established that oxidative stress/inflammation is a major factor for fat cell death so we will run a fat anti oxidant stack
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
I am not too worried about reductive stress as your cells will be under A LOT of stress during the initial weeks of healing
The periorbital region's limited vascularity means ischemia will be prolonged and the reperfusion ROS burst when vessels do grow in will be meaningful. The threshold for reductive stress in this context is shifted considerably compared to your healthy baseline state
The full stack I'll be running
- Tadalafil
- Pentoxifylline
- BPC-157 (Maybe TB500 too)
- Magnesium
- Low-dose naltrexone
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
- Rapamycin (First 72 hours possibly still need to research this a little more)
Day 1-5 (peak ischemia) - Full stack
Day 5-21 (neovascularisation phase) - This is where i would pull back on the antioxidants a bit , reducing NAC (or remove) removing Vitamin C during this window
3 weeks onward (Remodelling) - Can reintroduce full stack if desired or remove more if i want , less critical either way at this point


Thank you for reading and i hope this helped some of you considering fat grafting

 

[Includings]

Periorbital fat grafts are an affordable , very effective treatment to improving the eye area , there’s a good case to be made to even opt for this instead of implants.​

View attachment 44713

View attachment 44714


View attachment 44738









The main big issue with fat grafts is the survival rate and it’s particularly brutal in the peri orbital area (30-80% survival rate) , it’s common to overfill to try compensate for the fact you will lose significant fat however you can only do this to a certain extent before overfilling actually starts to cause more fat loss , this happens due to parcels of fat forming that are further from blood supply that will die (this kind of overfilling is a major cause for massive fat loss)


View attachment 44716


There is a 2mm rule Adipocytes within a 2mm range from the graft edge can receive sufficient nutrition through early neovascularization and survive , anything deeper than 2mm from the graft surface is essentially in an ischemic core
Even will overfilling correctly if you aren’t fortunate you will just see so much of the fat melt away
Beyond things like the obvious surgeon technique , managing by weight post op what else can be done to make fat grafts more likely to survive , first need to look into the route cause of the fat cell death
This being
1. Poor blood supply (sufficient blood supply is needed to restore nutritional support, transmit stem cells, and reduce oxygen deficit)
2. Mechanical stress
3. Oxidative stress/Inflammation
We can use a pharmaceuticals stack that promotes adipogenesis , blood flow and more to try counteract this as much as possible , of course your surgeon won’t tell you this as it loses them money when you don’t come back for a revision , there's a good chance they're also just as unaware JFL.
Most of these have minimal human data with mostly preclinical data however there is strong mechanistic plausibility for all as well as most being healthmaxxes in general so i see 0 reason not to run this

Vitamin E + Pentoxifylline​

I'm not going to waste time explaining the mechanisms of the actual drugs , this is dedicated to their application to fat grafting survival specifically


In this study they had recorded the effects of vitamin E and Pentoxyfilline on fat grafted mice (human fat grafted to them) and the drugs were actually administered orally

Vitamin E had showed significant effects in fat retention due to its reductions in oxidative stress and angiogenesis , surprisingly pentoxifylline did not but there is still good mechanistic reasoning to use pentoxifylline post fat grafting

This is because pentoxifylline increases red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation
In the context of fat grafting this matters because capillaries in that region are small and blood flow is compromised.
As RBCs become more flexible and plasma less viscous this increases oxygen delivery to the marginal zone of the graft where cells are on the edge of survival.

Vitamin E was effective through reducing oxidative stress and its effects on angiogenesis (forming of new blood vessels)



View attachment 44719 View attachment 44720 View attachment 44721View attachment 44722




These are rough estimates but when you scale for humans the dosage of pentoxifylline used was 8mg/kg , which is quite low (560mg for a 70kg male) , in real world 1200mg ED is common so we can go far above this dose in the study
The vitamin E was 0.9mg/kg60-65mg for a 70kg male which is still much lower than what you could run

PDE5 inhibitors​

PDE5 inhibitors improve the vasodilatory effect of NO through cGMP and have demonstrated beneficial effects in angiogenesis endothelial proliferation , remodelling and improvement of oxygen supply during healing.
They can also regulate vasodilation and clear oxidative stress components


Of all PDE5 inhibitors, tadalafil has the longest half-life at 17.5 hours making it the most practical for sustained perioperative coverage


This has some interesting data behind it though unfortunately is only in rodents and done in a way that isn't practical for us (method is patent protected and could be annoying to convince your surgeon regardless) though systematic PDE5 inhibitors are still is powerful.

A patent protected method demonstrates that PDE5 inhibitor treatment of grafts prior to harvest and transfer significantly improved revascularisation within the graft core at 1 and 2 weeks post grafting with sildenafil treated grafts maintaining virtually ALL volume over 12 weeks compared to rapid resorption in controls


View attachment 44729 View attachment 44730 View attachment 44731



As you can see the group with sildenafil not even tadalafil maintained pretty much double the fat
Of course this effect wouldn’t be near as profound practically when we use systematic PDE5 inhibitors rather than it being injected right into the subq fat as in this study however you will still get the benefits such as cGMP pathway enhancement , vasodilation , microcirculatory improvement , angiogenic signalling modulation and more.

BPC-157​

This one is mainly mechanistic speculation though should hold up and is worth adding IMO


'It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions'

Rapamycin​

Rapamycin is quite interesting for fat cell preservation

mTOR inhibition by rapamycin upregulates autophagy (the cellular self cleaning process)

In a fat graft context this is relevant because grafted adipocytes in the ischaemic zone (area lacking blood flow) are energy starved.
They can't access external nutrients or oxygen adequately due to lack of blood flow.
Autophagy allows these cells to essentially use their own damaged components to survive the ischaemic window until revascularisation occurs

There is actually some pretty recent direct fat graft research on this published in 'Aesthetic Plastic Surgery'

View attachment 44734 View attachment 44735

​

The timing logic here is important autophagy upregulation during the first 72 hour ischaemic window which can extend how long cells survive before vessels reach them

However mTOR is also required for normal adipogenesis and adipocyte differentiation , sustained mTOR inhibition could impair the regenerative replacement phase that follows initial survival

Rapamycin might be beneficial acutely in the ischaemic window but counterproductive during neovascularisation and onward , essentially only use during the first 72 hours post fat grafting.

Bonus : Botox​

Threw this one in as a bonus just because i found it interesting tbh though I imagine most people wont bother with doing this but Botox not only does it help promote angiogenesis through many mechanisms but is the first on this list to directly reduce mechanical stress which is another major factor , there isn't much data but has a lot of potential to work.


View attachment 44732

PPARY agonists​

PPARY agonists might seem like an obvious choice as it is the ‘master transcription factor for adipogenesis however they strongly promote adipogenesis in preadipocytes, but in mature adipocytes rosiglitazone actually decreases lipid content rather than increasing it.

Meaning do not use them though on paper it would seem like a no brainer


View attachment 44737

LDN (Low Dose Naltrexone)​

Naltrexone at any dose is a TLR4 antagonist
TLR4 is a pattern recognition receptor on macrophages and other immune cells that gets activated by free fatty acids and lipid debris from lysed adipocytes
When adipocytes lyse (break) in the graft they release free lipid droplets that activate TLR4 on macrophages triggering a sustained inflammatory response that damages neighbouring cells.
LDN blocking TLR4 directly interrupts this specific pathway.

Antioxidant stack ​

It is very established that oxidative stress/inflammation is a major factor for fat cell death so we will run a fat anti oxidant stack
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
I am not too worried about reductive stress as your cells will be under A LOT of stress during the initial weeks of healing
The periorbital region's limited vascularity means ischemia will be prolonged and the reperfusion ROS burst when vessels do grow in will be meaningful. The threshold for reductive stress in this context is shifted considerably compared to your healthy baseline state
The full stack I'll be running
- Tadalafil
- Pentoxifylline
- BPC-157 (Maybe TB500 too)
- Magnesium
- Low-dose naltrexone
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
- Rapamycin (First 72 hours possibly still need to research this a little more)
Day 1-5 (peak ischemia) - Full stack
Day 5-21 (neovascularisation phase) - This is where i would pull back on the antioxidants a bit , reducing NAC (or remove) removing Vitamin C during this window
3 weeks onward (Remodelling) - Can reintroduce full stack if desired or remove more if i want , less critical either way at this point


Thank you for reading and i hope this helped some of you considering fat grafting

Thread looks good, will give full read later

 

[jousefrzu]

looks good bookmarked

 

[Oryza]

Periorbital fat grafts are an affordable , very effective treatment to improving the eye area , there’s a good case to be made to even opt for this instead of implants.​

View attachment 44713

View attachment 44714


View attachment 44738









The main big issue with fat grafts is the survival rate and it’s particularly brutal in the peri orbital area (30-80% survival rate) , it’s common to overfill to try compensate for the fact you will lose significant fat however you can only do this to a certain extent before overfilling actually starts to cause more fat loss , this happens due to parcels of fat forming that are further from blood supply that will die (this kind of overfilling is a major cause for massive fat loss)


View attachment 44716


There is a 2mm rule Adipocytes within a 2mm range from the graft edge can receive sufficient nutrition through early neovascularization and survive , anything deeper than 2mm from the graft surface is essentially in an ischemic core
Even will overfilling correctly if you aren’t fortunate you will just see so much of the fat melt away
Beyond things like the obvious surgeon technique , managing by weight post op what else can be done to make fat grafts more likely to survive , first need to look into the route cause of the fat cell death
This being
1. Poor blood supply (sufficient blood supply is needed to restore nutritional support, transmit stem cells, and reduce oxygen deficit)
2. Mechanical stress
3. Oxidative stress/Inflammation
We can use a pharmaceuticals stack that promotes adipogenesis , blood flow and more to try counteract this as much as possible , of course your surgeon won’t tell you this as it loses them money when you don’t come back for a revision , there's a good chance they're also just as unaware JFL.
Most of these have minimal human data with mostly preclinical data however there is strong mechanistic plausibility for all as well as most being healthmaxxes in general so i see 0 reason not to run this

Vitamin E + Pentoxifylline​

I'm not going to waste time explaining the mechanisms of the actual drugs , this is dedicated to their application to fat grafting survival specifically


In this study they had recorded the effects of vitamin E and Pentoxyfilline on fat grafted mice (human fat grafted to them) and the drugs were actually administered orally

Vitamin E had showed significant effects in fat retention due to its reductions in oxidative stress and angiogenesis , surprisingly pentoxifylline did not but there is still good mechanistic reasoning to use pentoxifylline post fat grafting

This is because pentoxifylline increases red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation
In the context of fat grafting this matters because capillaries in that region are small and blood flow is compromised.
As RBCs become more flexible and plasma less viscous this increases oxygen delivery to the marginal zone of the graft where cells are on the edge of survival.

Vitamin E was effective through reducing oxidative stress and its effects on angiogenesis (forming of new blood vessels)



View attachment 44719 View attachment 44720 View attachment 44721View attachment 44722




These are rough estimates but when you scale for humans the dosage of pentoxifylline used was 8mg/kg , which is quite low (560mg for a 70kg male) , in real world 1200mg ED is common so we can go far above this dose in the study
The vitamin E was 0.9mg/kg60-65mg for a 70kg male which is still much lower than what you could run

PDE5 inhibitors​

PDE5 inhibitors improve the vasodilatory effect of NO through cGMP and have demonstrated beneficial effects in angiogenesis endothelial proliferation , remodelling and improvement of oxygen supply during healing.
They can also regulate vasodilation and clear oxidative stress components


Of all PDE5 inhibitors, tadalafil has the longest half-life at 17.5 hours making it the most practical for sustained perioperative coverage


This has some interesting data behind it though unfortunately is only in rodents and done in a way that isn't practical for us (method is patent protected and could be annoying to convince your surgeon regardless) though systematic PDE5 inhibitors are still is powerful.

A patent protected method demonstrates that PDE5 inhibitor treatment of grafts prior to harvest and transfer significantly improved revascularisation within the graft core at 1 and 2 weeks post grafting with sildenafil treated grafts maintaining virtually ALL volume over 12 weeks compared to rapid resorption in controls


View attachment 44729 View attachment 44730 View attachment 44731



As you can see the group with sildenafil not even tadalafil maintained pretty much double the fat
Of course this effect wouldn’t be near as profound practically when we use systematic PDE5 inhibitors rather than it being injected right into the subq fat as in this study however you will still get the benefits such as cGMP pathway enhancement , vasodilation , microcirculatory improvement , angiogenic signalling modulation and more.

BPC-157​

This one is mainly mechanistic speculation though should hold up and is worth adding IMO


'It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions'

Rapamycin​

Rapamycin is quite interesting for fat cell preservation

mTOR inhibition by rapamycin upregulates autophagy (the cellular self cleaning process)

In a fat graft context this is relevant because grafted adipocytes in the ischaemic zone (area lacking blood flow) are energy starved.
They can't access external nutrients or oxygen adequately due to lack of blood flow.
Autophagy allows these cells to essentially use their own damaged components to survive the ischaemic window until revascularisation occurs

There is actually some pretty recent direct fat graft research on this published in 'Aesthetic Plastic Surgery'

View attachment 44734 View attachment 44735

​

The timing logic here is important autophagy upregulation during the first 72 hour ischaemic window which can extend how long cells survive before vessels reach them

However mTOR is also required for normal adipogenesis and adipocyte differentiation , sustained mTOR inhibition could impair the regenerative replacement phase that follows initial survival

Rapamycin might be beneficial acutely in the ischaemic window but counterproductive during neovascularisation and onward , essentially only use during the first 72 hours post fat grafting.

Bonus : Botox​

Threw this one in as a bonus just because i found it interesting tbh though I imagine most people wont bother with doing this but Botox not only does it help promote angiogenesis through many mechanisms but is the first on this list to directly reduce mechanical stress which is another major factor , there isn't much data but has a lot of potential to work.


View attachment 44732

PPARY agonists​

PPARY agonists might seem like an obvious choice as it is the ‘master transcription factor for adipogenesis however they strongly promote adipogenesis in preadipocytes, but in mature adipocytes rosiglitazone actually decreases lipid content rather than increasing it.

Meaning do not use them though on paper it would seem like a no brainer


View attachment 44737

LDN (Low Dose Naltrexone)​

Naltrexone at any dose is a TLR4 antagonist
TLR4 is a pattern recognition receptor on macrophages and other immune cells that gets activated by free fatty acids and lipid debris from lysed adipocytes
When adipocytes lyse (break) in the graft they release free lipid droplets that activate TLR4 on macrophages triggering a sustained inflammatory response that damages neighbouring cells.
LDN blocking TLR4 directly interrupts this specific pathway.

Antioxidant stack ​

It is very established that oxidative stress/inflammation is a major factor for fat cell death so we will run a fat anti oxidant stack
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
I am not too worried about reductive stress as your cells will be under A LOT of stress during the initial weeks of healing
The periorbital region's limited vascularity means ischemia will be prolonged and the reperfusion ROS burst when vessels do grow in will be meaningful. The threshold for reductive stress in this context is shifted considerably compared to your healthy baseline state
The full stack I'll be running
- Tadalafil
- Pentoxifylline
- BPC-157 (Maybe TB500 too)
- Magnesium
- Low-dose naltrexone
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
- Rapamycin (First 72 hours possibly still need to research this a little more)
Day 1-5 (peak ischemia) - Full stack
Day 5-21 (neovascularisation phase) - This is where i would pull back on the antioxidants a bit , reducing NAC (or remove) removing Vitamin C during this window
3 weeks onward (Remodelling) - Can reintroduce full stack if desired or remove more if i want , less critical either way at this point


Thank you for reading and i hope this helped some of you considering fat grafting

Where do you find trusted clinics with high survival rates ?

 

[surgerymax]

Where do you find trusted clinics with high survival rates ?

Read papers they publish

 

[Nardicus102]

Post surgery stack

Thoughts on surgeons reporting false survival rates ?, most people are going back for another check up after 3 months if they were to go out of country for the procedure, cause you would need 3 months to even see final survival results

Are you considering going turkey route for this procedure ?

 

[Veridic]

Periorbital fat grafts are an affordable , very effective treatment to improving the eye area , there’s a good case to be made to even opt for this instead of implants.​

View attachment 44713

View attachment 44714


View attachment 44738









The main big issue with fat grafts is the survival rate and it’s particularly brutal in the peri orbital area (30-80% survival rate) , it’s common to overfill to try compensate for the fact you will lose significant fat however you can only do this to a certain extent before overfilling actually starts to cause more fat loss , this happens due to parcels of fat forming that are further from blood supply that will die (this kind of overfilling is a major cause for massive fat loss)


View attachment 44716


There is a 2mm rule Adipocytes within a 2mm range from the graft edge can receive sufficient nutrition through early neovascularization and survive , anything deeper than 2mm from the graft surface is essentially in an ischemic core
Even will overfilling correctly if you aren’t fortunate you will just see so much of the fat melt away
Beyond things like the obvious surgeon technique , managing by weight post op what else can be done to make fat grafts more likely to survive , first need to look into the route cause of the fat cell death
This being
1. Poor blood supply (sufficient blood supply is needed to restore nutritional support, transmit stem cells, and reduce oxygen deficit)
2. Mechanical stress
3. Oxidative stress/Inflammation
We can use a pharmaceuticals stack that promotes adipogenesis , blood flow and more to try counteract this as much as possible , of course your surgeon won’t tell you this as it loses them money when you don’t come back for a revision , there's a good chance they're also just as unaware JFL.
Most of these have minimal human data with mostly preclinical data however there is strong mechanistic plausibility for all as well as most being healthmaxxes in general so i see 0 reason not to run this

Vitamin E + Pentoxifylline​

I'm not going to waste time explaining the mechanisms of the actual drugs , this is dedicated to their application to fat grafting survival specifically


In this study they had recorded the effects of vitamin E and Pentoxyfilline on fat grafted mice (human fat grafted to them) and the drugs were actually administered orally

Vitamin E had showed significant effects in fat retention due to its reductions in oxidative stress and angiogenesis , surprisingly pentoxifylline did not but there is still good mechanistic reasoning to use pentoxifylline post fat grafting

This is because pentoxifylline increases red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation
In the context of fat grafting this matters because capillaries in that region are small and blood flow is compromised.
As RBCs become more flexible and plasma less viscous this increases oxygen delivery to the marginal zone of the graft where cells are on the edge of survival.

Vitamin E was effective through reducing oxidative stress and its effects on angiogenesis (forming of new blood vessels)



View attachment 44719 View attachment 44720 View attachment 44721View attachment 44722




These are rough estimates but when you scale for humans the dosage of pentoxifylline used was 8mg/kg , which is quite low (560mg for a 70kg male) , in real world 1200mg ED is common so we can go far above this dose in the study
The vitamin E was 0.9mg/kg60-65mg for a 70kg male which is still much lower than what you could run

PDE5 inhibitors​

PDE5 inhibitors improve the vasodilatory effect of NO through cGMP and have demonstrated beneficial effects in angiogenesis endothelial proliferation , remodelling and improvement of oxygen supply during healing.
They can also regulate vasodilation and clear oxidative stress components


Of all PDE5 inhibitors, tadalafil has the longest half-life at 17.5 hours making it the most practical for sustained perioperative coverage


This has some interesting data behind it though unfortunately is only in rodents and done in a way that isn't practical for us (method is patent protected and could be annoying to convince your surgeon regardless) though systematic PDE5 inhibitors are still is powerful.

A patent protected method demonstrates that PDE5 inhibitor treatment of grafts prior to harvest and transfer significantly improved revascularisation within the graft core at 1 and 2 weeks post grafting with sildenafil treated grafts maintaining virtually ALL volume over 12 weeks compared to rapid resorption in controls


View attachment 44729 View attachment 44730 View attachment 44731



As you can see the group with sildenafil not even tadalafil maintained pretty much double the fat
Of course this effect wouldn’t be near as profound practically when we use systematic PDE5 inhibitors rather than it being injected right into the subq fat as in this study however you will still get the benefits such as cGMP pathway enhancement , vasodilation , microcirculatory improvement , angiogenic signalling modulation and more.

BPC-157​

This one is mainly mechanistic speculation though should hold up and is worth adding IMO


'It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions'

Rapamycin​

Rapamycin is quite interesting for fat cell preservation

mTOR inhibition by rapamycin upregulates autophagy (the cellular self cleaning process)

In a fat graft context this is relevant because grafted adipocytes in the ischaemic zone (area lacking blood flow) are energy starved.
They can't access external nutrients or oxygen adequately due to lack of blood flow.
Autophagy allows these cells to essentially use their own damaged components to survive the ischaemic window until revascularisation occurs

There is actually some pretty recent direct fat graft research on this published in 'Aesthetic Plastic Surgery'

View attachment 44734 View attachment 44735

​

The timing logic here is important autophagy upregulation during the first 72 hour ischaemic window which can extend how long cells survive before vessels reach them

However mTOR is also required for normal adipogenesis and adipocyte differentiation , sustained mTOR inhibition could impair the regenerative replacement phase that follows initial survival

Rapamycin might be beneficial acutely in the ischaemic window but counterproductive during neovascularisation and onward , essentially only use during the first 72 hours post fat grafting.

Bonus : Botox​

Threw this one in as a bonus just because i found it interesting tbh though I imagine most people wont bother with doing this but Botox not only does it help promote angiogenesis through many mechanisms but is the first on this list to directly reduce mechanical stress which is another major factor , there isn't much data but has a lot of potential to work.


View attachment 44732

PPARY agonists​

PPARY agonists might seem like an obvious choice as it is the ‘master transcription factor for adipogenesis however they strongly promote adipogenesis in preadipocytes, but in mature adipocytes rosiglitazone actually decreases lipid content rather than increasing it.

Meaning do not use them though on paper it would seem like a no brainer


View attachment 44737

LDN (Low Dose Naltrexone)​

Naltrexone at any dose is a TLR4 antagonist
TLR4 is a pattern recognition receptor on macrophages and other immune cells that gets activated by free fatty acids and lipid debris from lysed adipocytes
When adipocytes lyse (break) in the graft they release free lipid droplets that activate TLR4 on macrophages triggering a sustained inflammatory response that damages neighbouring cells.
LDN blocking TLR4 directly interrupts this specific pathway.

Antioxidant stack ​

It is very established that oxidative stress/inflammation is a major factor for fat cell death so we will run a fat anti oxidant stack
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
I am not too worried about reductive stress as your cells will be under A LOT of stress during the initial weeks of healing
The periorbital region's limited vascularity means ischemia will be prolonged and the reperfusion ROS burst when vessels do grow in will be meaningful. The threshold for reductive stress in this context is shifted considerably compared to your healthy baseline state
The full stack I'll be running
- Tadalafil
- Pentoxifylline
- BPC-157 (Maybe TB500 too)
- Magnesium
- Low-dose naltrexone
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
- Rapamycin (First 72 hours possibly still need to research this a little more)
Day 1-5 (peak ischemia) - Full stack
Day 5-21 (neovascularisation phase) - This is where i would pull back on the antioxidants a bit , reducing NAC (or remove) removing Vitamin C during this window
3 weeks onward (Remodelling) - Can reintroduce full stack if desired or remove more if i want , less critical either way at this point


Thank you for reading and i hope this helped some of you considering fat grafting

If I could repost, I would

Amazing thread

 

[surgerymax]

Post surgery stack

Thoughts on surgeons reporting false survival rates ?, most people are going back for another check up after 3 months if they were to go out of country for the procedure, cause you would need 3 months to even see final survival results

Are you considering going turkey route for this procedure ?

I wouldn’t send completely fake survival rates but they market the best of their bunch , if their survival rate is 40-70% they’ll market as 70% , some cases people come out with as little as 15% of the grafted fat


Personally Thailand would be my #1 pick rn

 

[Nardicus102]

I wouldn’t send completely fake survival rates but they market the best of their bunch , if their survival rate is 40-70% they’ll market as 70% , some cases people come out with as little as 15% of the grafted fat


Personally Thailand would be my #1 pick rn

Would Upper n Lower eyelid fat graph actually reduce scalera show ? or they framing in the images above bit ?

and what are you thought on a canthopexy (NOT PLASTY) for someone who has a neutral tilt and wants a positive tilt, or do you think the neutral to positive tilt is low ROI. Most of the time its also combined with lower eyelid retraction as well.
n one of the more safer reversible procedures

 

[surgerymax]

Would Upper n Lower eyelid fat graph actually reduce scalera show ? or they framing in the images above bit ?

and what are you thought on a canthopexy (NOT PLASTY) for someone who has a neutral tilt and wants a positive tilt, or do you think the neutral to positive tilt is low ROI. Most of the time its also combined with lower eyelid retraction as well.
n one of the more safer reversible procedures

The scleral show is a bit nuanced , if you are lacking the boney structure under (inferior orbital rim projection) the weight and volume from the fat graft could possibly make your scleral show WORSE , from what i gather from your message it seems like you have a neutral ish canthal tilt and i’d suspect that to be the cause for your scleral show , you can imagine it as if the lower eyelid was a rope if this rope was stretched and pulled up by moving the anchor which is the lateral canthus up the tension from that would stretch the eyelid and straighten it and subsequent less scleral show , but if you add volume here without that support of the bone or canthus anchor there’s a chance you could look worse
We can see multiple cases of people lacking that boney support but their high set exocanthion providing this tighten causes them to have no scleral show and a straight lower eyelid
Atesh salih is an example that comes to mind


IMO canthopexy is solid especially if combined with certain techniques if u want to be safe you can go for it , im more of a go big or go home mentality , i like to take risks more tbh , if you want true structural reposition and increasing the strength of that anchoring of the lateral canthus as i mentioned u need a canthoplasty

 

[surgerymax]

Would Upper n Lower eyelid fat graph actually reduce scalera show ? or they framing in the images above bit ?

and what are you thought on a canthopexy (NOT PLASTY) for someone who has a neutral tilt and wants a positive tilt, or do you think the neutral to positive tilt is low ROI. Most of the time its also combined with lower eyelid retraction as well.
n one of the more safer reversible procedures

the guy in the front profile image also got canthoplasty and ptosis correction , not just fat grafted

The second guy we can see he still has the taping meaning he’s prob within the first 7 days ish post op , not very representative of his final result at all

 

[Nardicus102]

The scleral show is a bit nuanced , if you are lacking the boney structure under (inferior orbital rim projection) the weight and volume from the fat graft could possibly make your scleral show WORSE , from what i gather from your message it seems like you have a neutral ish canthal tilt and i’d suspect that to be the cause for your scleral show , you can imagine it as if the lower eyelid was a rope if this rope was stretched and pulled up by moving the anchor which is the lateral canthus up the tension from that would stretch the eyelid and straighten it and subsequent less scleral show , but if you add volume here without that support of the bone or canthus anchor there’s a chance you could look worse
We can see multiple cases of people lacking that boney support but their high set exocanthion providing this tighten causes them to have no scleral show and a straight lower eyelid
Atesh salih is an example that comes to mind


IMO canthopexy is solid especially if combined with certain techniques if u want to be safe you can go for it , im more of a go big or go home mentality , i like to take risks more tbh , if you want true structural reposition and increasing the strength of that anchoring of the lateral canthus as i mentioned u need a canthoplasty

Thank you that was probably the best analogy I ever heard.
and makes sense now

 

[syna]

pinned it , also heavily mirin this.

 

[Brian]

Periorbital fat grafts are an affordable , very effective treatment to improving the eye area , there’s a good case to be made to even opt for this instead of implants.​

View attachment 44713

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View attachment 44738









The main big issue with fat grafts is the survival rate and it’s particularly brutal in the peri orbital area (30-80% survival rate) , it’s common to overfill to try compensate for the fact you will lose significant fat however you can only do this to a certain extent before overfilling actually starts to cause more fat loss , this happens due to parcels of fat forming that are further from blood supply that will die (this kind of overfilling is a major cause for massive fat loss)


View attachment 44716


There is a 2mm rule Adipocytes within a 2mm range from the graft edge can receive sufficient nutrition through early neovascularization and survive , anything deeper than 2mm from the graft surface is essentially in an ischemic core
Even will overfilling correctly if you aren’t fortunate you will just see so much of the fat melt away
Beyond things like the obvious surgeon technique , managing by weight post op what else can be done to make fat grafts more likely to survive , first need to look into the route cause of the fat cell death
This being
1. Poor blood supply (sufficient blood supply is needed to restore nutritional support, transmit stem cells, and reduce oxygen deficit)
2. Mechanical stress
3. Oxidative stress/Inflammation
We can use a pharmaceuticals stack that promotes adipogenesis , blood flow and more to try counteract this as much as possible , of course your surgeon won’t tell you this as it loses them money when you don’t come back for a revision , there's a good chance they're also just as unaware JFL.
Most of these have minimal human data with mostly preclinical data however there is strong mechanistic plausibility for all as well as most being healthmaxxes in general so i see 0 reason not to run this

Vitamin E + Pentoxifylline​

I'm not going to waste time explaining the mechanisms of the actual drugs , this is dedicated to their application to fat grafting survival specifically


In this study they had recorded the effects of vitamin E and Pentoxyfilline on fat grafted mice (human fat grafted to them) and the drugs were actually administered orally

Vitamin E had showed significant effects in fat retention due to its reductions in oxidative stress and angiogenesis , surprisingly pentoxifylline did not but there is still good mechanistic reasoning to use pentoxifylline post fat grafting

This is because pentoxifylline increases red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation
In the context of fat grafting this matters because capillaries in that region are small and blood flow is compromised.
As RBCs become more flexible and plasma less viscous this increases oxygen delivery to the marginal zone of the graft where cells are on the edge of survival.

Vitamin E was effective through reducing oxidative stress and its effects on angiogenesis (forming of new blood vessels)



View attachment 44719 View attachment 44720 View attachment 44721View attachment 44722




These are rough estimates but when you scale for humans the dosage of pentoxifylline used was 8mg/kg , which is quite low (560mg for a 70kg male) , in real world 1200mg ED is common so we can go far above this dose in the study
The vitamin E was 0.9mg/kg60-65mg for a 70kg male which is still much lower than what you could run

PDE5 inhibitors​

PDE5 inhibitors improve the vasodilatory effect of NO through cGMP and have demonstrated beneficial effects in angiogenesis endothelial proliferation , remodelling and improvement of oxygen supply during healing.
They can also regulate vasodilation and clear oxidative stress components


Of all PDE5 inhibitors, tadalafil has the longest half-life at 17.5 hours making it the most practical for sustained perioperative coverage


This has some interesting data behind it though unfortunately is only in rodents and done in a way that isn't practical for us (method is patent protected and could be annoying to convince your surgeon regardless) though systematic PDE5 inhibitors are still is powerful.

A patent protected method demonstrates that PDE5 inhibitor treatment of grafts prior to harvest and transfer significantly improved revascularisation within the graft core at 1 and 2 weeks post grafting with sildenafil treated grafts maintaining virtually ALL volume over 12 weeks compared to rapid resorption in controls


View attachment 44729 View attachment 44730 View attachment 44731



As you can see the group with sildenafil not even tadalafil maintained pretty much double the fat
Of course this effect wouldn’t be near as profound practically when we use systematic PDE5 inhibitors rather than it being injected right into the subq fat as in this study however you will still get the benefits such as cGMP pathway enhancement , vasodilation , microcirculatory improvement , angiogenic signalling modulation and more.

BPC-157​

This one is mainly mechanistic speculation though should hold up and is worth adding IMO


'It activates several overlapping pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization. It also engages ERK1/2 signaling, facilitates endothelial and muscle repair, and exerts anti-inflammatory effects. These effects promote angiogenesis, fibroblast activity, and neuromuscular stabilization, particularly in poorly vascularized tissues such as tendons and myotendinous junctions'

Rapamycin​

Rapamycin is quite interesting for fat cell preservation

mTOR inhibition by rapamycin upregulates autophagy (the cellular self cleaning process)

In a fat graft context this is relevant because grafted adipocytes in the ischaemic zone (area lacking blood flow) are energy starved.
They can't access external nutrients or oxygen adequately due to lack of blood flow.
Autophagy allows these cells to essentially use their own damaged components to survive the ischaemic window until revascularisation occurs

There is actually some pretty recent direct fat graft research on this published in 'Aesthetic Plastic Surgery'

View attachment 44734 View attachment 44735

​

The timing logic here is important autophagy upregulation during the first 72 hour ischaemic window which can extend how long cells survive before vessels reach them

However mTOR is also required for normal adipogenesis and adipocyte differentiation , sustained mTOR inhibition could impair the regenerative replacement phase that follows initial survival

Rapamycin might be beneficial acutely in the ischaemic window but counterproductive during neovascularisation and onward , essentially only use during the first 72 hours post fat grafting.

Bonus : Botox​

Threw this one in as a bonus just because i found it interesting tbh though I imagine most people wont bother with doing this but Botox not only does it help promote angiogenesis through many mechanisms but is the first on this list to directly reduce mechanical stress which is another major factor , there isn't much data but has a lot of potential to work.


View attachment 44732

PPARY agonists​

PPARY agonists might seem like an obvious choice as it is the ‘master transcription factor for adipogenesis however they strongly promote adipogenesis in preadipocytes, but in mature adipocytes rosiglitazone actually decreases lipid content rather than increasing it.

Meaning do not use them though on paper it would seem like a no brainer


View attachment 44737

LDN (Low Dose Naltrexone)​

Naltrexone at any dose is a TLR4 antagonist
TLR4 is a pattern recognition receptor on macrophages and other immune cells that gets activated by free fatty acids and lipid debris from lysed adipocytes
When adipocytes lyse (break) in the graft they release free lipid droplets that activate TLR4 on macrophages triggering a sustained inflammatory response that damages neighbouring cells.
LDN blocking TLR4 directly interrupts this specific pathway.

Antioxidant stack ​

It is very established that oxidative stress/inflammation is a major factor for fat cell death so we will run a fat anti oxidant stack
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
I am not too worried about reductive stress as your cells will be under A LOT of stress during the initial weeks of healing
The periorbital region's limited vascularity means ischemia will be prolonged and the reperfusion ROS burst when vessels do grow in will be meaningful. The threshold for reductive stress in this context is shifted considerably compared to your healthy baseline state
The full stack I'll be running
- Tadalafil
- Pentoxifylline
- BPC-157 (Maybe TB500 too)
- Magnesium
- Low-dose naltrexone
- High dose melatonin
- Astaxanthin
- COQ10
- Vitamin C
- Vitamin E (Will be running anyway)
- NAC
- Glycine
- ALA (Alpha Lipoic Acid)
- Sulforaphane
- Rapamycin (First 72 hours possibly still need to research this a little more)
Day 1-5 (peak ischemia) - Full stack
Day 5-21 (neovascularisation phase) - This is where i would pull back on the antioxidants a bit , reducing NAC (or remove) removing Vitamin C during this window
3 weeks onward (Remodelling) - Can reintroduce full stack if desired or remove more if i want , less critical either way at this point


Thank you for reading and i hope this helped some of you considering fat grafting

Good

 

[sensitive sapphire]

botb worthy, fucking phenomenal