Table 1.

Examples of craniofacial disorders and corresponding unmet “regenerative” needs.

Disease	Tissue defects	Current strategies	Regenerative need
CONGENITAL
Craniosynostosis	Early bony suture fusion, aberrant skull growth if untreated	Successful bone regeneration after surgery if treated before age one	Promoting complete regeneration of the skull after surgery in all cases
Cleft lip/palate	Deficiency of palatal fusion including bone, muscle, and mucosa	Staged surgical repairs	Mucosa, without scarring that limits bone growth and causes maxillary deficiency
	Secondary deformities from inadequate growth after surgical intervention	Alveolar bone grafting	Elimination of bone graft donor site morbidity
Craniofacial microsomia	Deficient bone and soft tissue development of the face	Distraction osteogenesis Fat grafting Free tissue transfer	Multiple structures are hypoplastic: bone, muscle, skin, cartilage, nerve Achieving normal appearance
Microtia	Deficient and abnormal ear cartilage formation	Reconstruction with rib graft or alloplastic material	A functional reproduction of a normal ear without requiring a rib graft, and with less scarring
Moebius	Bilateral facial paralysis due to underdevelopment of cranial nerves	Free tissue transfer	Cranial nerve generation, or regeneration Development of target muscles
TRAUMATIC
Burn	Need for full skin coverage	Split-thickness skin grafting	Regenerated complete skin organ (epidermis, dermis, and appendages)
	Secondary deformities associated with scar contracture and loss of cartilaginous support	Fat and skin grafting to contractures	Supple, well-vascularized skin replacement with underlying cartilage framework
Fractures	Bone gaps occasionally present due to trauma, malunion, or non-union	Fixation Bone grafts	Regeneration of large defects
Soft tissue atrophy or tissue loss due to injury	May affect fat, muscle, skin, cartilages, mucosa, or nerves	Fat grafting Free tissue transfer	“Composite tissue” regeneration to replace subtle and complex form and function
		Skin grafting
		Face transplantation
ONCOLOGIC
Oropharyngeal or other facial cancers	Bone, soft tissue, muscle, and nerve may be radically resected	Free tissue transfer	“Composite tissue” regeneration to replace subtle and complex form and function
Radiation	Negatively affects skin and soft tissue elasticity and healing; causes osteoradionecrosis	Fat grafting Bone grafting	Skin regeneration Bone regeneration
IDIOPATHIC
Bell’s palsy	Facial nerve paralysis Secondary muscle denervation and atrophy	Micro-neurovascular free muscle transfer	Nerve and muscle regeneration to achieve complex function of multiple muscles
Parry-Romberg/progressive hemifacial atrophy	Progressive loss of soft tissue, nerve, muscle	Fat grafting	Fat regeneration Nerve and muscle regeneration
AGING
	Fat atrophy	Fat grafting	Rejuvenation of skin quality
	Loss of skin elasticity	Skin resurfacing	Rejuvenation of fat quantity and location
	Changes in skin pigmentation