Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells(ESPCs)-mediated articular cartilage repair

As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.

Re-evaluating the importance of carbohydrates as regenerative biomaterials

Introduction Carbohydrates are the most abundant natural biomaterials in the world.By interacting with cells of a variety of levels,they take part in essential functions of organisms including cellular communication,inflammation,infection development and disease.These carbohydrate–cell interactions occur on a variety of levels through glycoconjugates such as glycolipids,glycosaminoglycans(GAGs),glycoproteins and proteoglycans[1–4].The roles of carbohydrates in biological systems pose them as some of the most sought-after biomaterials.The use of these multifaceted molecules provides the opportunity to tailor desired responses depending on the target application[1–5].

Recent advances in regenerative biomaterials

Nowadays,biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues.The interdisciplinary progress has broadened the definition of‘biomaterials’,and a typical new insight is the concept of tissue induction biomaterials.The term‘regenerative biomaterials’and thus the contents of this article are relevant to yet beyond tissue induction biomaterials.This review summarizes the recent progress of medical materials including metals,ceramics,hydrogels,other polymers and bio-derived materials.As the application aspects are concerned,this article introduces regenerative biomaterials for bone and cartilage regeneration,cardiovascular repair,3D bioprinting,wound healing and medical cosmetology.Cell-biomaterial interactions are highlighted.Since the global pandemic of coronavirus disease 2019,the review particularly mentions biomaterials for public health emergency.In the last section,perspectives are suggested:(i)creation of new materials is the source of innovation;(ii)modification of existing materials is an effective strategy for performance improvement;(iii)biomaterial degradation and tissue regeneration are required to be harmonious with each other;(iv)host responses can significantly influence the clinical outcomes;(v)the long-term outcomes should be paid more attention to;(vi)the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed;(vii)public health emergencies call for more research and development of biomaterials;and(viii)clinical translation needs to be pushed forward in a full-chain way.In the future,more new insights are expected to be shed into the brilliant field-regenerative biomaterials.

Nanotechnology and bio-functionalisation for peripheral nerve regeneration

There is a high clinical demand for new smart biomaterials, which stimulate neuronal cell proliferation, migration and increase cell-material interaction to facilitate nerve regeneration across these critical-sized defects. This article briefly reviews several up-to-date published studies using Arginine-Glycine-Aspartic acid peptide sequence, nanocomposite based on polyhedral oligomeric silsesquioxane nanoparticle and nanofibrous scaffolds as promising strategies to enhance peripheral nerve regeneration by influencing cellular behaviour such as attachment, spreading and proliferation. The aim is to establish the potent manipulations, which are simple and easy to employ in the clinical conditions for nerve regeneration and repair.