Table 4.

Local Immunosuppression.

Large Animal Model	VCA model	IS	Experimental Groups	Results/Conclusion	Reference
Yorkshire Swine	Gracilis musculocutaneous flap	Hydrogen Sulfide	Group 1 (control) – 3-hour ischemic period without perfusion.	H2S perfusion associated with decreased levels of injury biomarkers and proinflammatory cytokines including creatine kinase, LDH, and AST	(69)
			Group 2 – 3-hour ischemic period with an interim perfusion of H2S.
Baboons	Skin	Slow-release (TyroSphere-encapsulated) topical formulations (cyclosporine or Tacrolimus)	Group 1 – Topical formulations applied directly to the STSGs only.	No graft survival benefit of topical treatment to either the STSG or wound bed	(66)
			Group 2 – Topical formulations applied to both the wound bed and the STSG.
Swine	Gracilis musculocutaneous flap	Hydrogen Sulfide	Group 1 (control) – 3 hours of cold ischemic time without treatment.	Local pretreatment with H2S delayed the onset of rejection both by clinical and histopathological assessment.	(67)
			Group 2 –Allografts pretreated with hydrogen sulfide prior to 3 hours cold ischemic time.
Swine	Forelimb VCA	Enzyme responsive, tacrolimus-eluting (TAC) hydrogel	Group 1 (control) – No treatment.	Group 1 – survival 6-7 days	(67)
			Group 2 – Low dose TAC hydrogel (49 mg).	Group 2 survival – 56-93 days
			Group 3 – High dose TAC hydrogel (91 mg).	Group 3 survival – 24-42 days
				Graft implanted TAC hydrogel allows for long term survival of orthotopic forelimb VCA in absence of systemic IS. Low dose treatment better tolerated than high dose treatment.

IS, immunosuppression; H2S, hydrogen sulfide; STSG, split thickness skin graft; VCA, vascularized composite allotransplant; AST, aspartate aminotransferase; LDH, lactate dehydrogenase.