Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

Abstract

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osteoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

Present Strategies for Critical Bone Defects Regeneration

“…It is difficult to maintain active drug delivery even proposed controlled drug delivery based on microparticles [123] Vascularized bone grafting Requires special skills; however, it is considered as procedure with limitations [124] Cell based Although application of MSCs as cellular material facilitates the construct innovation, there is still some issue with MSC preparation. Furthermore, natural bone is a composite of Nano hydroxyapatite particles with collagen nanofibers which impart the tissue's unique properties [138] Gene therapy Although, demonstrated successes in healing of large bone defects, but all have been applied on animal's models, without attentions to toxicology and other matters [139][140][141] Possibly those strategies have based on inappropriate understanding of bone defects healing. However, autografts still the best therapeutic strategy for large bone defects.…”

“…Although application of MSCs as cellular material facilitates the construct innovation, there is still some issue with MSC preparation. Furthermore, natural bone is a composite of Nano hydroxyapatite particles with collagen nanofibers which impart the tissue's unique properties [138].…”

Utilización de Células Troncales en Reconstrucción Cráneo-Maxilo-Facial en Humanos

“…La arquitectura facial esta compuesta por diferentes tejidos agrupados en unidades anatómicas complejas que otorgan al individuo la capacidad de interactuar con el medio, de alimentación, audición, olfato, etc. Cuando son afectadas estas estructuras, se producen severas alteraciones que tienen asociadas grandes cicatrices, desfiguramiento e importantes secuelas psicológicas (Tollemar et al, 2016). Si bien la cirugía progresó de forma significativa en el área reconstructiva con desarrollo de la transferencia microvascular de tejidos y nuevas técnicas de injerto óseos, todavía se mantiene como puntos desfavorables la necesidad de sitios donante con su consecuente morbilidad, así como los resultados de dichas reconstrucciones.…”

“…Generalmente estos defectos son reconstruidos con hueso autólogo o biomateriales como biopolímeros, implantes de polietileno, hueso demineralizado, hidroxiapatita, entre otros. Estos sustitutos tiene riesgos propios como la morbilidad del sitio donante y la cantidad de material en los autoinjertos; y el riesgo de infección y exposición en los biopolímeros; junto a esto la imposibilidad de crecer en menores de edad (Tollemar et al;Chung et al, 2012). La reconstrucción de estos defectos utilizando matriz (scaffolds) biodegradable junto a células cultivadas in vitro tendrían los efectos beneficiosos de cubrir una gran área de tejidos, sumado a su potencial de crecimiento que no interferiría con el desarrollo normal en menores de edad (Lendeckel et al).…”

Regenerative Medicine Weapons to Fight the Degenerative Defect of Musculoskeletal System Disorders

“…The concept of combining the stem cells, growth factors and scaffold was demonstrated to be efficient for regeneration of bone [1,2] , cartilage [3] , muscle [4] , tendon [5] and nerve [6] . Most of these studies was conducted at in vitro and in vivo level, supposing that will perform the same efficiency when be applied in the clinical cases.…”