Bone tissue engineering is becoming an ideal strategy to replace autologous bone grafts for surgical bone repair, but the multihierarchical complexity of natural bone is still difficult to emulate due to the lack of suitable biomaterials. Supramolecular peptide nanofiber hydrogels (SPNHs) are emerging biomaterials because of their inherent biocompatibility, satisfied biodegradability, high purity, facile functionalization, and tunable mechanical properties. This review initially focuses on the multihierarchical fabrications by SPNHs to emulate natural bony extracellular matrix. Structurally, supramolecular peptides based on distinctive building blocks can assemble into nanofiber hydrogels, which can be used as nanomorphology‐mimetic scaffolds for tissue engineering. Biochemically, bioactive motifs and bioactive factors can be covalently tethered or physically absorbed to SPNHs to endow various functions depending on physiological and pharmacological requirements. Mechanically, four strategies are summarized to optimize the biophysical microenvironment of SPNHs for bone regeneration. Furthermore, comprehensive applications about SPNHs for bone tissue engineering are reviewed. The biomaterials can be directly used in the form of injectable hydrogels or composite nanoscaffolds, or they can be used to construct engineered bone grafts by bioprinting or bioreactors. Finally, continuing challenges and outlook are discussed.

The repair of critical bone defects remains challenging worldwide. Three canonical pillars (biomaterial scaffolds, bioactive molecules, and stem cells) of bone tissue engineering have been widely used for bone regeneration in separate or combined strategies, but the delivery of bioactive molecules has several obvious drawbacks. Biophysical stimuli have great potential to become the fourth pillar of bone tissue engineering, which can be categorized into three groups depending on their physical properties: internal structural stimuli, external mechanical stimuli, and electromagnetic stimuli. In this review, distinctive biophysical stimuli coupled with their osteoinductive windows or parameters are initially presented to induce the osteogenesis of mesenchymal stem cells (MSCs). Then, osteoinductive mechanisms of biophysical transduction (a combination of mechanotransduction and electrocoupling) are reviewed to direct the osteogenic differentiation of MSCs. These mechanisms include biophysical sensing, transmission, and regulation. Furthermore, distinctive application strategies of biophysical stimuli are presented for bone tissue engineering, including predesigned biomaterials, tissue-engineered bone grafts, and postoperative biophysical stimuli loading strategies. Finally, ongoing challenges and future perspectives are discussed.

Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic.

Bioactive peptides and proteins (BAPPs) are promising therapeutic agents for tissue repair with considerable advantages, including multifunctionality, specificity, biocompatibility, and biodegradability. However, the high complexity of tissue microenvironments and their inherent deficiencies such as short half-live and susceptibility to enzymatic degradation, adversely affect their therapeutic efficacy and clinical applications. Investigating the fundamental mechanisms by which BAPPs modulate the microenvironment and developing rational delivery strategies are essential for optimizing their administration in distinct tissue repairs and facilitating clinical translation. This review initially focuses on the mechanisms through which BAPPs influence the microenvironment for tissue repair via reactive oxygen species, blood and lymphatic vessels, immune cells, and repair cells. Then, a variety of delivery platforms, including scaffolds and hydrogels, electrospun fibers, surface coatings, assisted particles, nanotubes, two-dimensional nanomaterials, and nanoparticles engineered cells, are summarized to incorporate BAPPs for effective tissue repair, modification strategies aimed at enhancing loading efficiencies and release kinetics are also reviewed. Additionally, the delivery of BAPPs can be precisely regulated by endogenous stimuli (glucose, reactive oxygen species, enzymes, pH) or exogenous stimuli (ultrasound, heat, light, magnetic field, and electric field) to achieve on-demand release tailored for specific tissue repair needs. Furthermore, this review focuses on the clinical potential of BAPPs in facilitating tissue repair across various types, including bone, cartilage, intervertebral discs, muscle, tendons, periodontal tissues, skin, myocardium, nervous system (encompassing brain, spinal cord, and peripheral nerve), endometrium, as well as ear and ocular tissue. Finally, current challenges and prospects are discussed.